Erythema infectiosum is an acute viral illness caused by Parvovirus B19. It is usually a mild flu-like illness and produces a maculopapular rash, appearing initially on the cheeks and then spreading towards extremities. The rash usually spares the palms and soles and gives a slapped appearance to the cheeks. It can be described as having a fishnet appearance on the body.

Fertilization occurs when the sperm reaches an egg released during ovulation. At the time of fertilization, the interaction of sperm with the zona pellucida stimulates the release of calcium. This process initiates a corona reaction that prevents polyspermy.

Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts which normally allow bile to drain from the gallbladder. Early cholangiographic changes can include fine or deep ulcerations of the common bile duct. As PSC progresses, segmental fibrosis develops within the bile ducts, with saccular dilatation of the normal areas between them, leading to the typical beads-on-a-string appearance seen on cholangiography. Although these strictures can be found anywhere on the biliary tree, the intrahepatic and extrahepatic bile ducts are simultaneously involved in the vast majority of cases.

Recurrent bacterial infections may be due to lack of B-cell function, consequently resulting in a lack of gamma globulins production. Once the maternal antibodies have depleted, the disease manifests with greater severity and is called x-linked agammaglobulinemia also known as ‘X-linked hypogammaglobulinemia’, ‘XLA’ or ‘Bruton-type agammaglobulinemia. it is a rare x linked genetic disorder that compromises the bodies ability to fight infections.
Acute leukaemia causes immunodeficiency but not so specific.
DiGeorge syndrome is due to lack of T cell function.
Aplastic anaemia and EBV infection does not cause immunodeficiency.

Von Hippel-Lindau syndrome is a genetic disorder inherited in autosomal dominant fashion. It is caused by the mutations of the VHL gene located on chromosome 3. The syndrome is characterized by the creation of multiple benign and malignant tumours involving various bodily systems along with the formation of numerous visceral cysts, including the renal and epididymal cysts. Down’s syndrome is associated with renal cysts, but it does not follow the autosomal dominant mode of inheritance, rather it is caused by non-disjunction of chromosome 21 during meiosis. Exomphalos is a defect of the medial abdominal wall leading to abnormal protrusion of abdominal viscera through it. It is not associated with renal cysts. Turner’s syndrome may be associated with renal cysts formation, but it is not transmitted in an autosomal dominant fashion. Polycystic kidney disease of childhood follows an autosomal recessive pattern of transmission.

Congenital TB symptoms typically develop during the second or third week of life and include poor feeding, poor weight gain, cough, lethargy, and irritability. Other symptoms include fever, ear discharge, and skin lesions.Signs of congenital TB include failure to thrive, icterus, hepatosplenomegaly, tachypnoea, and lymphadenopathy.

Congenital heart defects are common (40-50%)| they are frequently observed in patients with Down syndrome who are hospitalized (62%) and are a common cause of death in this aneuploidy in the first 2 years of life.The most common congenital heart defects are the following:- Endocardial cushion defect (43%), which results in atrioventricular septal defect (AVSD)/AV canal defect- Ventricular septal defect (32%)- Secundum atrial septal defect (10%)- Tetralogy of Fallot (6%)- Isolated patent ductus arteriosus (4%).About 30% of patients have more than one cardiac defect. The most common secondary lesions are patent ductus arteriosus (16%), atrial septal defect, and pulmonic stenosis (9%). About 70% of all endocardial cushion defects are associated with Down syndrome.Valve abnormalities, such as mitral valve prolapse or aortic regurgitation may develop in up to 40-50% of adolescents and adults who were born without structural heart disease.

Bleeding oesophageal varices secondary to portal hypertension can cause a massive gastrointestinal haemorrhage resulting in shock. Perforated ulcer is less likely in this age group. Mallory Weiss tear would not likely result in a massive haemorrhage. Aorto-intestinal fistula is more common in older patients with abdominal aneurysms. Boerhaave’s syndrome is a result of a ruptured oesophagus following excessive vomiting.

The clinical presentation and leucocytes on the urine dipstick is suggestive of a urinary tract infection. To confirm the diagnosis, urine should be sent for culture and sensitivity.

Based on the presented clinical scenario, the most probable diagnosis for the patient would be testicular torsion.Rationale:The gubernaculum is the structure responsible for aiding the descent of the testicles from the abdomen into the scrotum. The processus vaginalis precedes the descent of the testes and then undergoes closure. Abnormalities such as the persistence of a patent processus vaginalis, known as bell clapper deformity, predispose to testicular torsion.Other options:- Varicocele: Nutcracker syndrome occurs where the left renal vein becomes compressed in between the superior mesenteric artery and the aorta. Since the left gonadal vein drains into the left renal vein, this results in a varicocele. – Epididymitis and mumps orchitis are differentials for acute testicular pain but are not due to a defect in the processus vaginalis. – An incarcerated inguinal hernia presents mainly with signs of bowel obstruction which are not mentioned in the clinical scenario.The descent of testes:- Until the end of foetal life, the testicles are located within the abdominal cavity. – They are initially located on the posterior abdominal wall on a level with the upper lumbar vertebrae (L2). – Attached to the inferior aspect of the testis is the gubernaculum testis which extends caudally to the inguinal region, through the canal and down to the superficial skin. – It is interesting to note that both the testis and the gubernaculum are extra-peritoneal.- As the foetus grows, the gubernaculum becomes progressively shorter. It carries the peritoneum of the anterior abdominal wall (the processus vaginalis). As the processus vaginalis descends the testis is guided by the gubernaculum down the posterior abdominal wall and the back of the processus vaginalis into the scrotum.- By the third month of foetal life the testes are located in the iliac fossae, by the seventh they lie at the level of the deep inguinal ring.Usually, the processus vaginalis closes after birth but may persist predisposing to indirect hernias. On the other hand, a partial closure may result in the development of cysts on the cord.

The glossopharyngeal nerve is the primary sensory nerve for the tonsillar fossa. The lesser palatine nerve makes a smaller contribution. Because of this, otalgia may occur following tonsillectomy.Anatomical Rationale:Each palatine tonsil has two surfaces, a medial surface which projects into the pharynx and a lateral surface that is embedded in the wall of the pharynx.The primary arterial supply is from the tonsillar artery, a branch of the facial artery. Its veins pierce the constrictor muscle to join the external palatine or facial veins. The external palatine vein is immediately lateral to the tonsil, which may result in bleeding during a tonsillectomy.Lymphatic drainage is the jugulodigastric node and the deep cervical nodes.TonsillitisThe inflammation of tonsils is usually due to bacterial aetiology (50%) – group A Streptococcus, the remainder of the causes are viral.May be complicated by the development of an abscess (quinsy), which may distort the uvula.Indications for tonsillectomy include recurrent acute tonsillitis, and enlargement causing sleep apnoea.Dissection tonsillectomy is the preferred technique with haemorrhage being the most frequent complication. Delayed otalgia may occur owing to irritation of the glossopharyngeal nerve.

Craniopharyngiomas (also known as Rathke pouch tumours, adamantinomas or hypophyseal duct tumours) affect children mainly between the age of 5 and 10 years. It constitutes 9% of brain tumours affecting the paediatric population. These are slow-growing tumours which can also be cystic, and arise from the pituitary stalk, specifically the nests of epithelium derived from Rathke’s pouch. Histologically, this tumour shows nests of squamous epithelium which is lined on the outside by radially arranged cells. Calcium deposition is often seen with a papillary type of architecture.
ACTH-secreting pituitary adenomas are rare and mostly microadenomas. Paediatric astrocytoma’s usually occur in the posterior fossa. Although null cell adenomas can cause mass effect and give rise to the described symptoms, they are not suprasellar. Prolactinomas can also show symptoms of headache and disturbances in the visual field, however they are known to be small and slow-growing.

Damage to the left parietal lobe can result in what is called Gerstmann’s Syndrome. It includes right-left confusion, difficulty with writing (agraphia) and difficulty with mathematics (acalculia). It can also produce disorders of language (aphasia) and the inability to perceive objects normally (agnosia).Damage to the right parietal lobe can result in neglecting part of the body or space (contralateral neglect), which can impair many self-care skills such as dressing and washing. Right side damage can also cause difficulty in making things (constructional apraxia), denial of deficits (anosognosia) and drawing ability.Bi-lateral damage (large lesions to both sides) can cause Balint’s Syndrome, a visual attention and motor syndrome. This is characterized by the inability to voluntarily control the gaze (ocular apraxia), inability to integrate components of a visual scene (simultanagnosia), and the inability to accurately reach for an object with visual guidance (optic ataxia)Special deficits (primarily to memory and personality) can occur if there is damage to the area between the parietal and temporal lobes.Left parietal-temporal lesions can affect verbal memory and the ability to recall strings of digits. The right parietal-temporal lobe is concerned with non-verbal memory.Right parietal-temporal lesions can produce significant changes in personality.

Glandular fever (Infectious Mononucleosis) is caused by Epstein–Barr virus (EBV). Leucocytosis rules in infectious mononucleosis and thrombocytopenia is not an uncommon association. ESR is elevated in most of the cases. Paul-Bunnell test is a rapid test for infectious mononucleosis due to Epstein–Barr virus (EBV).

The sign being elicited in this patient is Nikolsky’s sign. Based on the findings, the patient is suffering from toxic epidermal necrolysis.Nikolskys sign: Rubbing the skin causes exfoliation of the outer layer and usually blistering within a few minutes. Other options:- Cullen’s sign: Periumbilical bruising due to intra-abdominal haemorrhage. If the discolouration is seen in the flanks, it is called Cullen’s sign. Underlying pathology includes ruptured ectopic pregnancy and haemorrhagic pancreatitis. – Forscheimer’s sign: It is a fleeting exanthem that is seen as small, red spots (petechiae) on the soft palate. Associated with rubella and glandular fever. Gorlin’s sign: It is the ability to touch the tip of the nose with the tongue. Increased incidence in children with connective tissue disorders, e.g. Ehler Danlos syndrome. – Auspitzs sign: These are small bleeding points left behind when psoriatic scales are lifted off. It is not a very sensitive or specific sign. Other cutaneous signs include:- Hair collar sign: It is a collar of hypertrichosis around an area of cranial dysraphism.- Hertoghe’s sign (Queen Anne’s sign): It is the loss of lateral one-third of eye-brows. It is associated with numerous conditions, including lupus, HIV, and hypothyroidism. – Dariers sign: It is the swelling, itching and erythema that occurs after stroking skin lesions of a patient with systemic mastocytosis or urticarial pigmentosa. – Dermatographism: Rubbing the skin causes a raised, urticarial lesion. – Koebners phenomenon: It is the appearance of new skin lesions in areas of trauma.- Breakfast, lunch, and dinner sign: Linear pathway of a group of three to five papules caused by the common bed bug, Cimex lectularius. – Buttonhole sign: In type 1 neurofibromatosis, neurofibromas can be invaginated with the finger back into the subcutis. The nodule will reappear after the release of pressure. The sign is also positive for dermatofibromas. – Crowe’s sign: Axillary freckling seen in type I neurofibromatosis.

The Glasgow Coma Scale, being inappropriate for use in children (especially below the age of 5) as they are unable to elicit the verbal response as per the adult GCS. Therefore, GCS for the paediatric age group was modified to Adelaide coma scale (ACS), which is stated as follows:Best Eye Response (as in adult scale):Spontaneous – 4To speech – 3To pain – 2No response – 1Best Verbal Response:Oriented – 5Words – 4Vocal sounds – 3Cries – 2No response – 1Best Motor Response (as in adult scale):Obeys commands – 5Localises pain – 4Flexion to pain – 3 Extension to pain – 2No response – 1 The described child scores:Eye response – 1| Verbal response – 3| Motor response – 4Thus, bringing the total ACS score to 8.

Pulmonary arterial hypertension (PH) is noted in 9 to 35 % of patient with a secundum type ASD. The haemodynamic definition of PH is a mean pulmonary arterial pressure (mPAP) of ≥25 mmHg at rest by means of right heart catheterization. In ASD, The findings on physical examination depend on the degree of left-to-right shunt and its hemodynamic consequences, which, in turn, depends on the size of the defect, the diastolic properties of both ventricles, and the relative resistance of the pulmonary and systemic circulations.Blood flow across the atrial septal defect (ASD) does not cause a murmur at the site of the shunt because no substantial pressure gradient exists between the atria. However, ASD with moderate-to-large left-to-right shunts results in increased right ventricular stroke volume across the pulmonary outflow tract creating a crescendo-decrescendo systolic ejection murmur. This murmur is heard in the second intercostal space at the upper left sternal border.Patients with large left-to-right shunts often have a rumbling mid-diastolic murmur at the lower left sternal border because of increased flow across the tricuspid valve.ASD is an acyanotic lesion. Thus, the patient should be normally saturated. In the rare case of severe pulmonary arterial hypertension, atrial shunt reversal (Eisenmenger syndrome) may occur, leading to cyanosis and clubbing

Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive defects in enzymes that are responsible for cortisol, aldosterone, and, in very rare cases, androgen synthesis. All forms of CAH are characterized by low levels of cortisol, high levels of ACTH, and adrenal hyperplasia. The exact clinical manifestations depend on the enzyme defect. The most common form of CAH, which is caused by a deficiency of 21β-hydroxylase, presents with hypotension, ambiguous genitalia, and virilization (in the female genotype), and/or precocious puberty (in both males and females). It is further characterized by hyponatremia, hyperkalaemia, and metabolic acidosis. Increased levels of 17-hydroxyprogesterone confirm the diagnosis of 21β-hydroxylase deficiency. Treatment of CAH involves lifelong glucocorticoid replacement therapy. Patients with a 21β-hydroxylase deficiency also require mineralocorticoid replacement with fludrocortisone. Complications of CAH include severe hypoglycaemia, adrenal insufficiency, and/or a failure to thrive.

The mesonephric duct is one of the paired embryogenic tubules that drain the primitive kidney (mesonephros) to the cloaca. It also gives off a lateral branch forming the ureteric bud. In both the male and the female the Wolffian duct develops into the trigone of the urinary bladder. When the ducts are exposed to testosterone during embryogenesis, male sexual differentiation occurs: the mesonephric duct develops into the rete testis, the ejaculatory ducts, the epididymis, the ductus deferens and the seminal vesicles.

Cataracts in infants are most commonly identified by an abnormal red reflex. Due to the high risk of amblyopia in unilateral cataracts, prompt referral to a paediatric ophthalmologist is indicated. Bilateral cataracts may occur in association with several syndromes or diseases, and these children require evaluation for these systemic disorders.Retinoblastoma is rare, but it is the most common primary intraocular tumour in children. About 80% of cases are diagnosed before age 4, with a median age at diagnosis of 2 years. It most frequently presents due to an abnormal red reflex. It is one of the few life-threatening disorders encountered in paediatric ophthalmology. Intraocular retinoblastoma is very treatable, but the mortality for metastatic disease is high. Identification of tumours before systemic spread is critical. Most children with large unilateral tumours will require enucleation (surgical removal of the eye), but the eye and vision may sometimes be preserved if the tumours are identified when they are small.

A lymphangioma is a swelling or mass that occurs mainly in the head, neck, and mouth. Lymphangiomas are the result of a congenital condition and are usually apparent at birth, or at least by the time a person is 2 years old. It is rare in adult population and when detected, it can be treated with surgical excision. Branchial cyst in most cases does not transilluminate which lymphangioma does.

At 7 months, children are expected to sit briefly leaning forward on their hands, reach and grasp objects, transfer objects from hand to hand, and babble. Children are usually expected to wave goodbye or grasp objects with their fingers or thumb at around 10 months and older.

Unconjugated bilirubin is conjugated to glucuronic acid in the hepatocyte. Conjugated bilirubin passes into the enterohepatic circulation and the bilirubin which evades this system is metabolised by bacteria, primarily in the large intestine, to urobilinogen, then stercobilinogen and eventually oxidised to stercobilin. Stercobilin gives faeces its brown colour.

In the first few years of life the developing sensory inputs are important. Hearing is essential for speech and language development and may be delayed when a child cannot hear. Therefore any child with a family history of hereditary deafness should be screened. From about 4-6months babies are able to laugh and babble when excited or unhappy. By the age of 9 months the child should be able to bring together groups of same sound syllables and be able to say one or two words by the 1st birthday. If a child is unable to babble by 10-12 years, it may indicate hearing impairment. By the age of 2 a child should be able to speak in 1 or 2 word phrases and often repeats phrases used by others, known as Echolalia.

Unless given IV, a drug must cross several semipermeable cell membranes before it reaches the systemic circulation. Drugs may cross cell membranes by diffusion, amongst other mechanisms. The rate of diffusion of a substance is proportional to the difference in the concentration of the diffusing substance between the two sides of the membrane, the temperature of the solution, the permeability of the membrane and, in the case of ions, the electrical potential difference between the two sides of the membrane.

Tinea corporis is a type of dermatophytosis, caused by Trichophyton or Microsporum. The disease is highly contagious and rapidly spreads to all the areas of the body. It produces an itchy rash with a central area of clearance surrounded by raised scaly borders. Diagnosis can be made by skin examination. All other mentioned conditions do not affect the palms and soles.

One of the options of Psoriasis treatment is vitamin D analogues i.e. calcipotriol. Acne is exacerbated by steroids. Erythema nodosum can be caused by various diseases and the treatment of the primary condition resolves the symptoms. Lipomas requires surgery, whereas Steven-Johnson syndrome requires use of steroids and eliminating the culprit drug, which is one of the most common causes.

Intussusception is the most suggested case here based on the child’s symptoms. The urgent course of treatment is to bring the child to a paediatric surgical unit. If air reduction attempts fail, surgery will have to be done. Risk factors for intussusception include viral infection and intestinal lymphadenopathy.

The most commonly requested biochemistry tests for renal function are the urea and electrolytes. They supply important information when it comes to homeostasis and excretion. Glomerular filtration rate is also the essential standard marker of kidney health and is assessed by checking the creatinine levels. In this case as the child has lost fluids and electrolytes, this test will indicate the extent of the loss and allow for more appropriate replacement.

In case control studies, observational studies are made to compare two groups, individuals with a certain condition, to those without the condition, with all other factors being equal. In the situation presented by the question, the study was to determine whether a prior risk factor, a low birth weight, was associated with later developing adolescent hypertension, using a paired t-test to statistically determine whether there was indeed a significant association between the two conditions. Case control studies only help to draw associations between two groups and therefore cannot indicate causation. In this scenario we are also not given the p value to determine whether the association is statistically significant. Therefore there is not enough evidence to conclude whether or not birthweight affects the development of adolescent hypertension.

Ehlers-Danlos Syndrome (EDS) is a group of genetic connective tissue disorders with over 13 clinical subtypes. Hyper-mobility is common to many of these subtypes. Vascular EDS is identified by thin, translucent skin prone to easy bleeding, as well as the risk of early arterial rupture, gastrointestinal perforation and uterine rupture. Those affected have dysmorphic features including a thin nose and lips, sunken cheeks and large eyes. The other features including| atrophic scars, a dominant family history, hyper extensible skin and kyphoscoliosis are not specific to vascular EDS and overlap in many of the subtypes.

Intussusception causes abdominal pain leading to painful lower GI bleeding. Intussusception is a condition in which part of the intestine folds into the section next to it. It most commonly involves the small bowel and rarely the large bowel. Intussusception doesn’t usually require surgical correction. 80% of cases can be both confirmed and reduced using barium, water-soluble or air-contrast enema.However, up to 10% of cases can experience recurrence within 24 hours after reduction, warranting close monitoring during this period.Most children have self-limiting and minor bleeds. However, children with massive bleeds will need emergency care and stabilisation.The various causes of lower GI bleeding in neonates include:- Anal fissures- Milk protein or soy allergy- Intussusception- Volvulus- Coagulopathies including haemorrhagic disease of the new-born- Arteriovenous malformations- Necrotising enterocolitis- Hirschsprung enterocolitis- Meckel’s diverticulitis- Drugs (NSAIDs, heparin, indomethacin used for patent duct closure, dexamethasone)The various causes of lower GI bleeding in children aged between 1 month to 2 years include:- Infection- Anal fissures- Intussusception- Malrotation with volvulus- Milk protein or soy allergy- Polyp- Meckel’s diverticulum- Duplication cyst- Foreign body- AV malformation- Colitis of immune deficiency- Tumour- HaematomaThe causes of lower GI bleeding in children older than 2 years include:- Polyp- Inflammatory bowel disease (IBD)- Infectious diarrhoea (caused by Escherichia coli and Shigella)- Intussusception- Haemangiomas- Arteriovenous malformations- Vasculitis- Tumour

Mature human breast milk is nutrient and enzyme rich, optimal for human infants. The average calorie requirement for a one month old infant is about 100kcal/kg/day. Lactose, the most abundant carbohydrate, is beneficial for the baby’s developing gastro intestinal system. The proteins in mature milk are mostly whey (as compared to a high proportion of casein in cows milk), which digests easily. Other proteins found in breast milk include immunoglobulin, lysozyme, lactoferrin and lactalbumin. In terms of micronutrients, while Vitamin K levels are low in breast milk, Vitamin A, C and E are found in higher concentrations than in cow’s milk.

The presenting features and the surgical site provided in the clinical scenario are highly suggestive of ipsilateral hypoglossal nerve injury.Note:Three cranial nerves may be injured during submandibular gland excision.- Marginal mandibular branch of the facial nerve- Lingual nerve- Hypoglossal nerveHypoglossal nerve damage may result in the paralysis of the ipsilateral aspect of the tongue. The nerve itself lies deep to the capsule surrounding the gland and should not be injured during an intracapsular dissection. The lingual nerve is probably at higher risk of injury. However, the effects of lingual nerve injury are predominantly sensory rather than motor.Thus, the most appropriate answer is the hypoglossal nerve.

Tuner’s syndrome is not associated with arachnodactyly.Arachnodactyly is seen in the following conditions:- Marfan syndrome- Homocystinuria- Ehlers-Danlos syndrome- Congenital contractural arachnodactylyOther rare syndromes include:- Loeys-Dietz syndrome- Antley-Bixler syndrome- Marden-Walker syndrome- Lujan-Frinz syndrome- Haim-Munk syndrome- Marden-Walker syndrome- Spondylocostal dysostosis

Adrenal insufficiency is a serious medical condition that leads to inadequate secretion of corticosteroids. There are three main types of adrenal insufficiency: primary, secondary, and tertiary, based on the location of the abnormality. Primary adrenal insufficiency is caused by any pathology located inside the adrenal glands. The most common cause of primary adrenal insufficiency is Addison’s disease, which is an autoimmune condition. Adrenoleukodystrophy is an X-linked neurodegenerative disease that also causes primary adrenal insufficiency. Secondary adrenal insufficiency is caused by any pathological impairment of the pituitary gland or the hypothalamus. The important causes of secondary adrenal insufficiency include iatrogenic (steroid use), pituitary tumours like craniopharyngioma, and conditions leading to panhypopituitarism like Sheehan’s syndrome. Tertiary adrenal insufficiency is caused by the deficiency of the corticotropin-releasing hormone. Hypoparathyroidism does not cause adrenal insufficiency.

Cluster headaches present with unilateral severe headache that may be associated with ipsilateral cranial autonomic symptoms including| lacrimation, rhinorrhoea, ophthalmic injection, and occasionally, Horner syndrome (ipsilateral miosis, ptosis, and facial anhidrosis).

By the age of 3 months Jasmine should startle to loud noises, recognise her parents voices and turn to them when they are speaking, and should quiet down or smile at the sound of a familiar voice when crying. She should also cry when she is uncomfortable or irritated. By the time Jasmine is 9 months old she would begin to understand and respond to the word ‘no’ as well as other easy commands. She would be able vocalise and babble with repetitive sounds, and imitate adults’ playful sounds. She would be much less likely startled by loud noises.

The most common cause of acute urticaria is a viral infection. Individual lesions typically are short-lived and last less than 24 hours. Urticaria can be due to or can be made worse by cold temperatures. One of the other causes of urticaria is salicylic acid.

According to the NICE guidelines, the frequency of stool passage is considered constipation when two or more of the following findings are present: Fewer than 3 stools a week, large hard stools, stools that resemble rabbit droppings| symptoms associated with defecation including distress, bleeding or straining| a history of previous episodes of a precious/current anal fissure. The child in the scenario fails to meet the criteria, and has no evidence of impacted faeces on examination. The best course of action is to encourage the parents to give the child more water to prevent dehydration, and feed the child a fibre rich diet including fruits, vegetables and high fibre bread.

Neonatal hyperbilirubinemia is a common clinical condition and can be categorized as conjugated and unconjugated hyperbilirubinemia. Conjugated hyperbilirubinemia results from obstructive or hepatocellular causes mainly. The causes of conjugated hyperbilirubinemia include inborn errors of metabolism like galactosemia and aminoaciduria, obstruction from choledochal cysts, and biliary atresia. Long term TPN also leads to conjugated hyperbilirubinemia. Spherocytosis is a hereditary condition belonging to the group of haemolytic anaemias, resulting from plasma membrane protein deficiency. This defect of the RBC plasma membrane decreases their life span, making them osmotically fragile and prone to haemolysis. This leads to an increase in the unconjugated bilirubin levels, with a risk of developing kernicterus.

The average amount of energy required by a well preterm baby in a thermo-neutral environment is 50/kcal/kg to maintain essential body functions while it takes about 70 kcal/kg/day for optimal growth. It is important to ensure that enough proteins are given per calorie to limit catabolism and promote cell building. Caloric need usually increases when the baby is ill.

Based on the studies, genetic factors are responsible for approximately 60 % DVT cases. Factor V (FV) Leiden which is the most common cause of inherited thrombophilia, predisposes patients to DVT because of resistance to protein C.The heritable causes of deep vein thrombosis, from most to least common are:Factor V LeidenProthrombin G20210A variantProtein C deficiencyProtein S deficiencyAntithrombin deficiencyVon Willebrand disease and thalassaemia are not causes of DVT.

The presentation is suggestive of nephrotic syndrome. A trial of corticosteroids is the first step in treatment of idiopathic nephrotic syndrome. Diuretics are useful in managing symptomatic oedema. Cyclosporin and cyclophosphamide are indicated in frequently relapsing and steroid dependant disease.

Synchronized IMV (SIMV) with pressure support, used in the alert infant. SIMV guarantees a minimum minute volume while allowing the patient to trigger spontaneousbreaths at a rate and volume determined by the patient. Extra breaths are boosted with pressure support. Tidal Volume (Vt) is normally approximately 6-10 mL/kg and 4-6 ml/kg in the preterm.Respiratory rate (RR) is usually 30-60 BPM. Tidal volume and respiratory rate are relatedto respiratory minute volume as follows: Vm(mL/min) = Vt x RR .This baby is overventilated with a low CO2. Tidal volumes should generally be targeted at 4–6 ml/kg and this baby is being targeted at 9 ml/kg which exposes the baby to damage to the distal airways from this ventilation which can lead to bronchopulmonary dysplasia.

Vesicoureteric reflex (VUR) is described as the retrograde flow of urine from the bladder into the ureter due to an incompetent uterovesical junction. In primary VUR the lower urinary tract functions normally, while secondary VUR is associated with a poorly functioning lower urinary tract. The incidence of VUR is highest in new-born girls. They can present with hydronephrosis, or urinary tract infections.

Congenital hypothyroidism (CH) is inadequate thyroid hormone production in new-born infants. It can occur because of an anatomic defect in the gland, an inborn error of thyroid metabolism, or iodine deficiency.CH is the most common neonatal endocrine disorder, and historically, thyroid dysgenesis was thought to account for approximately 80% of cases. However, studies have reported a change in the epidemiology, with a doubling in incidence to around 1 in 1500 live new-borns.​Infants with congenital hypothyroidism are usually born at term or after term. Symptoms and signs include the following:Decreased activityLarge anterior fontanellePoor feeding and weight gainSmall stature or poor growthJaundiceDecreased stooling or constipationHypotoniaHoarse cryProlonged neonatal jaundice or unconjugated hyperbilirubinemia

Precocious puberty is the development of secondary sexual characteristics before the age of 8 in females, and 9 in males. The first sign of early puberty in females is breast enlargement, followed by the appearance of pubic and axillary hair, and finally menarche, 2-3 years after the onset of thelarche. Precocious puberty is caused by the premature activation of the hypothalamic-pituitary-gonadal axis where FSH and LH levels are raised. Less common is the gonadotrophin independent form, which is due to excess sex hormones, but low FSH and LH levels.

Among the provided options, we would expect a normally developing 18-month-old child to be able to carry toys while walking.At 18 months, a normally developing child will show the following gross motor abilities:- walks with the feet slightly apart- runs carefully with the head held high- pushes and pulls objects around the floor- walks upstairs if the hand is held- kneels on a flat surface without support- carry toys while walking.Other options:- Intentionally kicking a ball is a skill typically acquired by 2.5 years, not 18 months.- Jumping with two feet together from a small step is usually acquired by 2.5 years, not 18 months.- Propelling a tricycle forwards by pushing with the feet on the floor is a milestone generally acquired by 2 years, not 18 months.- Throwing a small ball overhand without falling is a milestone for children aged 2 years, not 18 months.

History of fever is suggestive of an infective focus. A straight nasal bones excludes a nasal bone fracture. A nasal septal abscess is defined as a collection of pus between the cartilage or bony septum and it is an uncommon disease which should be suspected in a patient with acute onset of nasal obstruction and recent history of nasal trauma.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease. The Lisch nodule represents one of the most common NF1 ocular manifestations.NF1 is caused by a genetic mutation which can cause tumours to grow on nerve endings| these cutaneous neurofibromas are benign tumours which grow on the skin, often first appearing during the hormonal changes that occur in teenage years. They vary in size and can appear anywhere on the body. The number of neurofibromas present differs greatly between individuals and over a lifetime Café au lait spots (coffee coloured birthmarks) are often the first and most common sign of NF1, and these are often found at birth and are usually evident by 2 years of age.Other features of NF1 can include Lisch nodules of the iris (small pigmentation in the iris which causes no disturbance to vision), skin-fold freckling (freckling/pigmentation in the groyne and armpits), plexiform neurofibromas (or sub cutaneous neurofibromas) which are diffuse tumours that grow along a nerve and are found in at least 25 % of people with NF1, optic gliomas (tumour of the optic nerve), and skeletal complications including pseudarthrosis and scoliosis. Macrocephaly (large head size) is also common, and short stature is found in around a third of people with NF1. Rare complications include a risk of malignancy, organs being compromised by neurofibromas, seizures, and hypertension.

Amniotic fluid is the protective liquid that surrounds the fetus in utero. It prevents the fetus from injury, protects the umbilical cord from compression, and provides necessary nutrients and a medium for growth and movement. Amniotic fluid originates from the maternal plasma initially, but by 16th week of gestation, fetal kidneys start making urine which contributes to further production of the amniotic fluid. Amniotic fluid contains a number of chemical substances including hormones, tumour markers, nutrients, electrolytes, and immunoglobulins. Main substances found in amniotic fluid include carbohydrates, proteins, lipids, lactoferrin, insulin-like growth factor, granulocyte colony-stimulating factor, erythropoietin, etc. Interleukin-1 is not a component of AF.

After birth, the infant takes its first breath and is exposed to a myriad of stimuli. The pulmonary vessels dilate, and pulmonary vascular resistance (PVR) decreases remarkably while the systemic vascular pressure rises above the PVR. This allows blood from the right ventricle to enter the lungs for oxygenation. In most cases, this increased oxygenation, along with other factors, causes the ductal wall to constrict and the ductus arteriosus to close functionally. As left-sided pressures rise higher than right-sided pressures, the foramen ovale functionally closes. With the clamping of the umbilical cord and the cessation of blood flow, pressures in the portal sinus decrease. This causes the muscle in the sinus wall near the ductus venosus to contract. The lumen of the duct becomes filled with connective tissue, and, in two months, the ductus venosus becomes a fibrous strand embedded in the wall of the liver, thus establishing adult circulation.

Puberty is when a child’s body begins to develop and change as they become an adult.The average age for girls to begin puberty is 11, while for boys the average age is 12.It’s completely normal for puberty to begin at any point from the ages of 8 to 14. The process can take up to 4 years.

Hyposplenism usually occurs after the surgical removal of the spleen or in pathological processes where the splenic tissue is replaced with abnormal tissue. It is often associated with diseases such as sickle cell disease, Coeliac disease, SLE and Dermatitis Herpetiformis. Myxoedema however bears no known association with hyposplenism. Patients with hyposplenism are at risk of fulminant bacterial infection.

Milestones of 3 years old:Social and Emotional:Copies adults and friends Shows affection for friends without prompting Takes turns in games Shows concern for crying friend Understands the idea of “mine” and “his” or “hers” Shows a wide range of emotions Separates easily from mom and dad May get upset with major changes in routineDresses and undresses self Language/Communication:Follows instructions with 2 or 3 steps Can name most familiar things Understands words like “in,” “on,” and “under” Says first name, age, and sexNames a friend Says words like “I,” “me,” “we,” and “you” and some plurals (cars, dogs, cats) Talks well enough for strangers to understand most of the time Carries on a conversation using 2 to 3 sentences Cognitive (learning, thinking, problem-solving):Can work toys with buttons, levers, and moving parts Plays make-believe with dolls, animals, and people Does puzzles with 3 or 4 pieces Understands what “two” means Copies a circle with pencil or crayon Turns book pages one at a time Builds towers of more than 6 blocks Screws and unscrews jar lids or turns door handle Movement/Physical Development:Climbs well Runs easily Pedals a tricycle (3-wheel bike) Walks up and down stairs, one foot on each step

Stridor is a sign of upper airway obstruction. One of the most common causes of stridor in children is laryngomalacia. In the absence of laryngomalacia, stridor presenting with respiratory distress, few chest signs and no preceding coryza symptoms or fever all point to the inhalation of a foreign object. This is common in children, with a peak incidence between 1 and 2 years of age. This child did not present with a high temperature, usually indicative of epiglottitis . The incidence of epiglottis has decreased due to the H. Influenza type b vaccine. Additionally viral croup and bronchiolitis present with upper respiratory tract infection. Asthma rarely presents with stridor but is rather associated with a wheeze.

Homonymous hemianopia (HH) is a visual field defect involving either two right or the two left halves of the visual field of both eye. It results from the damage of the visual pathway in its suprachiasmatic part. The causes of HH include stroke, brain tumours, head injuries, neurosurgical procedures, multiple sclerosis and miscellaneous conditions. HH result in a severe visual impairment and affect a variety of cognitive visual functions. Patients with HH frequently have difficulties with reading and scanning scenes in sufficiently rapid fashion to make sense of things as a whole. They stumble, fall or knock objects in their surroundings, since they cannot see them and they are frequent surprised that somebody or something suddenly appeared in their visual field. The prognosis of visual field deficit recovery is highly variable and depends on the cause and severity of brain nd optic pathway injury.

Iron deficiency anaemia has the following laboratory characteristics: low haemoglobin, a low serum iron, a low serum ferritin, a low transferrin saturation, and a high total iron-binding capacity.

Due to malaria’s incubation period being between 7 and 30 days, malaria prophylaxis cannot provide a patient with confirmed protection. Prophylaxis treatment also often fails. The symptoms such as neck stiffness, fever, and vomiting are also consistent with the cerebral malaria diagnosis.

The differentials of the child’s condition are likely to include an Iron deficiency anaemia, or a hemoglobinopathy such as sickle cell disease or thalassemia based on the presentation of pallor, growth failure and easy fatiguability. While the full blood count and film present a hypochromic microcytic anaemia with reticulocytosis, the normal serum ferritin levels rule out iron deficiency anaemia. Thalassemia is to be suspected over sickle cell disease as the patient comes from the Mediterranean region known for a high incidence of thalassemia. Sickle cell anaemia also tends to present with normocytic normochromic red blood cells, with many sickled cells. Vitamin B12 deficiency and Aplastic anaemia are ruled out as they present with a macrocytic anaemia, and a decrease in white blood cells, platelets and red blood cells respectively.

Severe cyanotic heart diseases such as pulmonary stenosis, transposition of the great vessels, hypoplastic left heart syndrome and truncus arteriosus all run the risk of a poor prognosis for a neonate. To continue the supply of oxygen the ductus arteriosus must be kept patent. This can be done with the immediate administration of Prostaglandin E1 as a temporary measure until a surgical intervention such as an atrial septostomy can be done. The closure of the duct can subsequently be initiated with the administration of indomethacin and oxygen.

The child has symptoms and signs suggestive of an inflammatory arthropathy. This is why he should firstly be referred for an eye exam to exclude iritis or treat it if present. – Amblyopia is not directly associated with inflammatory arthropathies unless they had recurrent ocular involvement.- Blepharitis is not an associated finding in a child with inflammatory arthropathy.- Episcleritis may occur, and is often non-sight threatening, and therefore would not be the main cause for concern.- Optic neuropathy in juvenile inflammatory arthritis has been reported, although it is rare.

Thyroglossal cyst is the most common congenital thyroid anomaly which is clinically significant and affects women more than men. It is a vestigial remnant of developing thyroid. Although the thyroglossal cyst can develop anywhere along the thyroglossal duct, the most common site is in the midline between the isthmus of thyroid and hyoid bone, or just above the hyoid. Thyroglossal cysts are also associated with ectopic thyroid tissue. Clinically, the cyst moves upward with protrusion of the tongue. Rarely, the persistent duct can become malignant (thyroglossal duct carcinoma) where the cancerous cells arise in the ectopic thyroid tissue that are deposited along the duct. Exposure to radiation is a predisposing factor.

90% of patients with meconium ileus have cystic fibrosis (CF). Indeed, in 10 – 15% of cases of CF, the patient presents with meconium ileus.

The boy is most probably a type 1 diabetic patient. Such a condition can affect the behaviour and psychological state of a young child reflected in their behaviour. The parents should seek the help of a clinical psychologist.

Precocious puberty is the attainment of normal pubertal biochemical and physical features at an abnormally early age. The age cut-offs commonly used to define precocious puberty are 8 years for females and 9 years for males. Precocious puberty may be central (true) or peripheral (false) based on the aetiology. Central precocious puberty is due to the premature activation of the hypothalamic-pituitary-gonadal axis, which in turn leads to the development of secondary sexual characteristics at an earlier than usual age. The best laboratory investigation to diagnose central precocious puberty is a gonadotropin-releasing hormone stimulation test, which is regarded as the gold standard. It requires the collection of multiple blood samples at different time points to measure FSH and LH levels. If the LH levels increase to >8IU/L after stimulation with GnRH, then the diagnosis of central precocious puberty is confirmed.

Vagus nerve lesions will affect the gag reflex since the pharyngeal muscles are innervated by it.The vagal nerve (10th cranial nerve ) is a mixed nerve carrying motor efferents and sensory afferents. The nerve conducts five distinct qualities, which are carried along general visceral efferent fibres (parasympathetic innervation of pharyngeal, laryngeal, bronchial, and gastrointestinal mucosa), general visceral afferent fibres (sensory information from the thoracic and abdominal viscera, the aortic body, aortic arch), special visceral afferent fibres (carry the taste of the epiglottal region), general somatic afferent fibres (carry sensation from the external auditory meatus, outer tympanic membrane, back of the ear, part of meninges, pharynx), and along special visceral efferent fibres, which innervate skeletal muscles of the pharynx and larynx. Skeletal muscles innervated by the vagal nerve include the cricothyroid, levator veli palatini, salpingopharyngeus, palatoglossal, palatopharyngeus pharyngeal constrictor, and the laryngeal muscles (except cricothyroid). Innervation of these muscles is involved during speech or opening of the larynx during breathing. Efferent parasympathetic fibres control heart rate, peristalsis, and sweating. Stimulation of the efferent parasympathetic fibres lowers heart rate or blood pressure. 80–90% of the vagal fibres are afferent, only 10–20% are efferent fibresPhysical exam of the 10th cranial nerve includes eliciting the gag reflex (The gag reflex involves a brisk and brief elevation of the soft palate and bilateral contraction of pharyngeal muscles evoked by touching the posterior pharyngeal wall.), to look if the uvula is deviated from the side of the lesion, if there is failure of palate elevation upon phonation, and evaluation of speech impairment.In case of bilateral vagal nerve lesions, heart rate and breath rate may be increased. The somatic sensory function can be assessed by testing the sensibility of the external auditory meatus.

The normal human pancreas contains about 1,000,000 islets. The islets consist of four distinct cell types, of which three (alpha, beta, and delta cells) produce important hormones| the fourth component (C cells) has no known function.The most common islet cell, the beta cell, produces insulin.The alpha cells of the islets of Langerhans produce an opposing hormone, glucagon.The delta cells produce somatostatin, a strong inhibitor of somatotropin, insulin, and glucagon.

Increasing the volume of the TV and the child’s loss of hearing may suggest that he has otitis media with effusion but the fever and the ear pain and fever strongly points to otitis externa as the diagnosis.

Torsade de pointes is an uncommon and distinctive form of polymorphic ventricular tachycardia (VT) characterized by a gradual change in the amplitude and twisting of the QRS complexes around the isoelectric line.Conditions associated with torsade include the following:Electrolyte abnormalities – Hypokalaemia, hypomagnesemia, hypocalcaemiaEndocrine disorders – Hypothyroidism, hyperparathyroidism, pheochromocytoma, hyperaldosteronism, hypoglycaemiaCardiac conditions – Myocardial ischemia, myocardial infarction, myocarditis, bradyarrhythmia, complete atrioventricular (AV) block, takotsubo cardiomyopathyIntracranial disorders – Subarachnoid haemorrhage, thalamic hematoma, cerebrovascular accident, encephalitis, head injuryNutritional disorders – Anorexia nervosa, starvation, liquid protein diets, gastroplasty and ileojejunal bypass, celiac diseaseRisk factors for torsade include the following:Congenital long QT syndromeFemale genderAcquired long QT syndrome (causes of which include medications and electrolyte disorders such as hypokalaemia and hypomagnesemia)BradycardiaBaseline electrocardiographic abnormalitiesRenal or liver failure

Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or by maternal uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells (eggs and sperm) or in early embryonic development. Affected people typically have no history of the disorder in their family.Rarely, a genetic change responsible for Prader-Willi syndrome can be inherited. For example, it is possible for a genetic change that abnormally inactivates genes on the paternal chromosome 15 to be passed from one generation to the next.Prader-Willi syndrome is a complex genetic condition that affects many parts of the body. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, affected individuals develop an insatiable appetite, which leads to chronic overeating (hyperphagia) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes (the most common form of diabetes).

Cricothyroidectomy is done in life threatening condition, where an incision is made in cricothyroid membrane to establish a patent airway.

Fetal alcohol syndrome (FAS) is a common yet under-recognized condition resulting from maternal consumption of alcohol during pregnancy. The diagnosis of fetal alcohol syndrome (FAS) is based on findings in the following 3 areas: (1) characteristic facial anomalies (see image below), (2) growth retardation (intrauterine growth restriction and failure to have catch-up growth), and (3) CNS involvement (cognitive impairment, learning disabilities, or behavioural abnormalities).Key characteristic craniofacial abnormalities include the following:- Smooth philtrum- Thin, smooth vermilion border of the upper lipShort palpebral fissures (< 10th percentile for age)Other craniofacial abnormalities are as follows:- Midface hypoplasia- Microphthalmia- Strabismus- PtosisCNS and neurobehavioral abnormalities include the following:- Microcephaly- Intellectual impairment (mild-to-moderate mental retardation)- Cognitive impairment- Developmental delay- Irritability in infancy- Hyperactivity in childhood or attention deficit hyperactivity disorder (ADHD)- Seizures- Delayed or deficient myelination- Agenesis or hypoplasia of the corpus callosumSkeletal abnormalities include the following:- Radioulnar synostosis- Flexion contractures- Camptodactyly- Aberrant palmar creases, especially hockey-stick palmar crease- Clinodactyly- Klippel-Feil anomaly- Hemivertebrae- Scoliosis- Dislocated jointsOther major congenital anomalies include the following:- Cleft palate- Heart defects- Renal anomalies- DiGeorge sequenceFunctional problems include the following:- Refractive problems (e.g., myopia, astigmatism)- Hearing lossGrowth deficiency includes the following:- Infant small for gestational age (< 10th percentile for weight or length)- Postnatal growth deficiency

From the given scenario, the extraocular muscle affected in the child is superior oblique muscle. Point to remember:All of the extraocular muscles are supplied by the oculomotor nerve (3rd cranial nerve), except superior oblique (trochlear nerve/4th cranial nerve) and lateral rectus (abducens nerve/6th cranial nerve).The superior oblique muscle causes the eye to move downwards and medially. The unopposed inferior oblique, in this case, causes the eye to deviate upwards and medially. Children tend to tilt their head (torticollis) to the side opposite to the affected eye with their chin down toward the shoulder, and their face turned away from the affected side to decrease the diplopia.

The most probable cause for the patient’s presenting symptoms is encephalitis secondary to measles infection.Encephalitis:Encephalitis occurs in 1 per 1000 measles cases. It usually presents within 1–14 days of the rash, usually day 5. It may present with fever, headache, vomiting, stiff neck, meningeal irritation, drowsiness, seizures, reduced consciousness| 15% will have neurological sequelae| 10% mortality.Other options:- Acute disseminated encephalomyelitis occurs in 1 per 1000 measles cases. It is thought to be a postinfectious immune response. Clinical manifestations include fever, headache, neck stiffness, seizures and mental status changes. It could fit this presentation although it tends to present in the recovery phase of measles infection, typically two weeks after the exanthem. In contrast, encephalitis tends to occur within a few days of the rash.- The history is not that of a typical febrile seizure as it lasted >15 minutes. He has also not recovered consciousness at 4 hours. The diazepam should have been eliminated within 4 hours and so should no longer be contributing to his reduced level of consciousness. Also, the history states the recent diagnosis of measles, and so complications of measles should be considered.- Intracranial bleed secondary to thrombocytopenia: Measles is not known to cause thrombocytopenia.- Subacute sclerosing panencephalitis (also known as Dawson’s encephalitis): This is an extremely rare complication of measles. It is a progressive degenerative disease of the central nervous system that occurs 7–10 years after a measles infection. The treatment for SSPE is mainly intraventricular interferon therapy through an Ommaya reservoir. The prognosis is poor, and it is usually fatal.

The most probable diagnosis for this patient is bilateral retractile testes. This a normal phenomenon in some pre-pubertal boys. Rationale:Testicular descent can continue until about 3-months of age. The pre-pubertal testis is small enough that with activation of the cremasteric reflex, they can enter the inguinal canal. This in itself is a normal finding providing the testis can be brought into the scrotum without tension and does not require surgical correction. With time the testis will lie within the scrotum. Orchidopexy for true undescended testis can be performed from 6-months of age. It is also warranted if the testes remain undescended or intra-abdominally leading to infertility.Other options:- An ascending testis is one, typically, following hernia or orchidopexy surgery that was in the testis but with time is within the inguinal canal and cannot be brought into the scrotum. Orchidopexy is required for this.- No surgery is required as when the testis enlarges with puberty it will remain within the scrotum.- The testes can be brought into the scrotum. Therefore they are not undescended.- The testes are retractile not ascending| ascending testis cannot be brought into the scrotum and would require orchidopexy.

Excessive weight loss is generally indicative of suboptimal feeding, and infants with excessive weight loss are potentially dehydrated or at risk of dehydration.Jaundice associated with suboptimal breastfeeding– this is classically associated with weight loss >10% and a vicious cycle of sleepiness that in turn leads to further poor feeding. In the absence of clinical signs of dehydration, no evidence suggests that overhydration is helpful. If the infant is dehydrated, hydration should be given as clinically indicated. However, if the infant can tolerate oral feeding, oral hydration with a breast milk substitute is likely to be superior to intravenous hydration because it reduces enterohepatic circulation of bilirubin and helps wash bilirubin out of the bowel.

Fanconi anaemia, a rare autosomal recessive condition, presents with congenital abnormalities and defective hemopoiesis. Clinical signs include pallor and bruising. Hypoplasia of the thumbs and radial hypoplasia are two of the most common congenital abnormalities. Conductive deafness is also common. Those with Fanconi anaemia have a higher risk for developing acute myeloid leukaemia.

Alopecia is a scalp condition characterized by either overall baldness or patches of hair loss over the head. It can be broadly classified as scarring alopecia and non-scarring alopecia. Non-scarring is the most common type and is seen in various conditions like nutritional deficiencies, alopecia areata, hypothyroidism, tinea capitis, and SLE. Scarring alopecia is commonly seen in cases of discoid lupus erythematosus, which is a common cause of widespread inflammatory and scarring lesions all over the body and scalp.

Hypertrophic villi is a response to chronic irritation by allergic reactions

Before the test, the patient was likely to have the disease being tested for. Their pre test odds were 2, making them twice as likely to have the disease. After testing positive, their pretest odds of 2 and the likelihood ratio of 3 are multiplied to produce 6 as the post test odds. The patient is now 6 times as likely to have the disease after the test. Likelihood ratios above 10 or below 0.1 are strong evidence to rule in and rule out a diagnosis. The negative likelihood ratio is not known here, but does not subtract from the interpretation of the outcomes in this patient.

Tuberous sclerosis, an autosomal dominant disorder, may present with a variety of symptoms, including seizures, developmental delay, behavioural problems, skin abnormalities, and lung and kidney disease. Hamartomas are often associated.

Pierre Robin sequence is a condition present at birth, in which the infant has micrognathia, a tongue that is placed further back than normal (glossoptosis), and cleft palate. This combination of features can lead to difficulty breathing and problems with eating early in life. Pierre Robin sequence may occur isolated or be associated with a variety of other signs and symptoms (described as syndromic). The exact causes of Pierre Robin syndrome are unknown. The most common otic anomaly is otitis media, occurring 80% of the time, followed by auricular anomalies in 75% of cases. Hearing loss, mostly conductive, occurs in 60% of patients, while external auditory canal atresia occurs in only 5% of patients.

The presence of anti-endomysial antibodies confirms the diagnosis of Celiac disease, which is the primary cause of illness in this patient. The sweat chloride test is performed with cystic fibrosis.

The correct answer is triple X syndrome with a genotype of XXX and an almost normal female phenotype. The extra X chromosome is inactive. The final phenotype of an individual is determined after normal sexual and gonadal differentiation, a process that involves several genes located on chromosomes X and Y. Disorders of sexual differentiation result in cases of ambiguous genitalia and are caused by a number of genetic abnormalities. Among these disorders is the turner syndrome with a genotype of 45X0, characterized by gonadal dysgenesis and ovarian failure. DAX-1 gene mutation leads to congenital adrenal hypoplasia and hypogonadotropic hypogonadism, which results in virilization of female external genitalia. Campomelic dysplasia results from mutation of the SOX-9 gene, leading to 46XY sex reversal. Danys-Drash syndrome is characterized by disordered sexual development in affected males due to the mutated WT-1 gene, which also causes Wilm’s tumour.

Patients with HIV have a deficiency of CD4 lymphocytes which are also known as helper T cells (Th). They are involved with antigen-specific responses as well as delayed-type hypersensitivity. The risk of developing P. jiroveci pneumonia is greatest with a CD4 count of 200 x 109/l or below.

Urine culture and sensitivity is used to diagnose a urinary tract infection (UTI). A mid-stream clean catch urine sample is the most common type of sample collected. It is important to follow the clean catch process to have accurate results from an uncontaminated sample. Urine cultures can also check for infections of the bladder or kidney.

The organisms most likely to cause post-splenectomy sepsis include:- Streptococcus pneumoniae- Haemophilus influenzae- MeningococciEncapsulated organisms carry the most significant pathogenic risk following splenectomy. Hyposplenism:It may complicate certain medical conditions where splenic atrophy occurs or maybe the result of medical intervention such as splenic artery embolization and splenectomy for trauma. The diagnosis of hyposplenism is difficult, and while there may be peripheral markers of the splenectomised state (e.g. Howell-Jolly bodies), these are neither 100% sensitive or specific. The most sensitive test is a radionucleotide labelled red cell scan.It dramatically increases the risk of post-splenectomy sepsis, particularly with encapsulated organisms. Since these organisms may be opsonized, but this then goes undetected at an immunological level due to loss of the spleen. For this reason, individuals are recommended to be vaccinated and have antibiotic prophylaxis.Key recommendations:- All those with hyposplenism or prior to an elective splenectomy should receive pneumococcal, Haemophilus type b and meningococcal type C vaccines. These should be administered two weeks before or two weeks following splenectomy. The vaccine schedule for meningococcal disease primarily consists of a dose of Men C and Hib at two weeks and then a dose of the MenACWY vaccine one month later. Those aged under two may require a booster at two years. A dose of pneumococcal polyvalent polysaccharide vaccine (PPV) is given at two weeks. A conjugate vaccine (PCV) is offered to young children. The PCV is more immunogenic but covers fewer serotypes. Boosting PPV is either guided by serological measurements (where available) or by routine boosting doses at five-yearly intervals.Annual influenza vaccination is recommended in all cases- Antibiotic prophylaxis is offered to all. The risk of post-splenectomy sepsis is highest immediately following splenectomy. Individuals with an inadequate response to pneumococcal vaccination are another high-risk group. High-risk individuals should be counselled to take penicillin or macrolide prophylaxis. Those at low risk may choose to discontinue therapy. All patients should be advised about taking antibiotics early in the case of intercurrent infections.- Asplenic individuals travelling to malaria-endemic areas are at high risk and should have both pharmacological and mechanical protection.

This girl most probably has Turner’s syndrome, which is caused by the absence of one set of genes from the short arm of one X chromosome.Turner syndrome is a lifelong condition and needs lifelong oestrogen replacement therapy. Oestrogen is usually started at age 12-15 years. Treatment can be started with continuous low-dose oestrogens. These can be cycled in a 3-weeks on, 1-week off regimen after 6-18 months| progestin can be added later.In childhood, growth hormone therapy is standard to prevent short stature as an adult.Fetal ovarian development seems to be normal in Turner syndrome, with degeneration occurring in most cases around the time of birth so pulsatile GnRH and luteinising hormone would be of no use.

Neurogenic shock is a devastating consequence of spinal cord injury (SCI), also known as vasogenic shock. Injury to the spinal cord results in sudden loss of sympathetic tone, which leads to the autonomic instability that is manifested in hypotension, bradyarrhythmia, and temperature dysregulation. Spinal cord injury is not to be confused with spinal shock, which is a reversible reduction in sensory and motor function following spinal cord injury. Neurogenic shock is associated with cervical and high thoracic spine injury. Early identification and aggressive management are vital in neurogenic shock to prevent secondary spinal injury.

Sturge-Weber syndrome is a genetic condition affecting various blood vessels. I causes brain, eye, and skin abnormalities, including three major features: port-wine birthmark, leptomeningeal angioma, and glaucoma. Most people are born with a port-wine birthmark that is usually located on the face, including the eyelid.

In the pattern of mendelian inheritance, X- linked dominant inheritance means that all who inherit the X chromosome will present with the condition. In the case of maternal x-linked inheritance sons and daughters have an equal chance of inheriting the condition as there is a 50% chance of inheriting the defective X chromosome from their mother as opposed to a non affected X chromosome from their father. However in paternal X-linked dominant inheritance, sons will be unaffected as they inherit a Y chromosome from their father while daughters are sure to inherit the defective X-chromosome.

Presentation can vary by individual. Early stages are often characterized by malaise, fatigue, and lethargy. One to 3 months of inadequate intake can lead to anaemia, myalgia, bone pain, easy bruising (Figure 3), swelling, petechiae, perifollicular haemorrhages, corkscrew hairs, gum disease, poor wound healing, mood changes, and depression. Perifollicular haemorrhages and easy bruising are often first seen in the lower extremities, as capillary fragility leads to an inability to withstand hydrostatic pressure. Late stages of scurvy are more severe and life threatening| common manifestations include generalized oedema, severe jaundice, haemolysis, acute spontaneous bleeding, neuropathy, fever, convulsions, and death.

The elemental diet is a medically supervised, sole nutrition dietary management given to individuals with moderate to severe impaired gastrointestinal function for 14-21 days.The diet consists of macronutrients broken down into their elemental form requiring little to no digestive functionality allowing time for the gut to rest. Elemental formulations are believed to be entirely absorbed within the first few feet of small intestine.

The clinical presentation of lichen planus has several variations, as follows:- Hypertrophic lichen planus- Atrophic lichen planus- Erosive/ulcerative lichen planus- Follicular lichen planus (lichen planopilaris)- Annular lichen planus- Linear lichen planus- Vesicular and bullous lichen planus- Actinic lichen planus- Lichen planus pigmentosus- Lichen planus pemphigoides

Melanoma, a highly malignant tumour arising from melanocytes, is the most common life-threatening dermatological disease. Risk factors include UV radiation exposure, particularly in light-skinned individuals that are easily sunburned, increasing age, family history, and immunosuppression. Lesions that are suspicious for melanoma should be excised with complete margins. Radical excision is not routinely undertaken for diagnostic purposes and therefore if subsequent histopathological assessment determines that the lesion is a melanoma a re-excision of margins may be required.Margins of excision-Related to Breslow thicknessLesions 0-1mm thick – 1cmLesions 1-2mm thick – 1- 2cm (Depending upon site and pathological features)Lesions 2-4mm thick – 2-3 cm (Depending upon site and pathological features)Lesions >4 mm thick – 3cm

Marfan syndrome (MFS) is a spectrum of disorders caused by a heritable genetic defect of connective tissue that has an autosomal dominant mode of transmission. The defect itself has been isolated to the FBN1 gene on chromosome 15, which codes for the connective tissue protein fibrillin. Abnormalities in this protein cause a myriad of distinct clinical problems, of which the musculoskeletal, cardiac, and ocular system problems predominate.The most severe of these clinical problems include aortic root dilatation and dissection, which have historically been the causative factors in early patient demise. Skeletal deformities such as thoracolumbar scoliosis, thoracic lordosis, and pectus excavatum, may lead to pulmonary difficulties that include restrictive airway disease and cor pulmonale if the deformities are progressive and untreated. Finally, blindness may result from unrecognized and untreated glaucoma, retinal detachment, and cataracts.The skeleton of patients with MFS typically displays multiple deformities including arachnodactyly (i.e., abnormally long and thin digits), dolichostenomelia (i.e., long limbs relative to trunk length), pectus deformities (i.e., pectus excavatum and pectus carinatum), and thoracolumbar scoliosis. In the cardiovascular system, aortic dilatation, aortic regurgitation, and aneurysms are the most worrisome clinical findings. Mitral valve prolapse that requires valve replacement can occur as well. Ocular findings include myopia, cataracts, retinal detachment, and superior dislocation of the lens.Other features:General tall staturePectus excavatum or carinatumDisproportionately long, slender armsDisproportionately long digitsArachnodactylyFinger contracturesReduced extension of elbows (< 170 degrees)Protrusio acetabuli (intrapelvic displacement of the acetabulum)Pes planus (flat feet)HypermobilityArthralgiaJoint instabilityScoliosisKyphosisDolichocephalia (elongated face)High arched palateDental crowdingDental malocclusion

Polyuria is defined as a total increase in the urine output or > 2L/m2 of daily urine produced in children. Polyuria can be a symptom of a vast number of medical conditions. The commonest and most important disease having polyuria as the main symptom is diabetes mellitus. Nephrogenic and central diabetes insipidus also results in polyuria along with polydipsia. Other conditions that lead to an increase in the urine output are renal failure, acute tubular necrosis, and exposure to high altitude. Hyperkalaemia does not result in polyuria| rather hypokalaemia can be an associated finding with polyuria in the case of diuretic abuse.

This is probably a case of protein-induced allergic proctitis, due to dietary protein transmitted through the mother to the breast-fed child. The mother should go on a milk-free and soya-free diet but continue to breast-feed.