Toe walking refers to a pattern of walking in which the infants walk on the balls of their feet, without putting the heel of the feet on the ground. It is considered normal under the age of 2 years, but if it continues beyond that, it can signify some underlying pathology. The diseases that can be associated with toe walking include unilateral hip dislocation, Spinal tumours, Duchenne muscular dystrophy, prematurity, and cerebral palsy. Waardenburg’s syndrome is an autosomal dominant disorder, causing sensorineural deafness, and heterochromatic irises. Toe walking is not a feature.

Bacterial meningitis (including meningococcal meningitis, Haemophilus influenzae meningitis, and staphylococcal meningitis) is a neurologic emergency that is associated with significant morbidity and mortality. Initiation of empiric antibacterial therapy is therefore essential for better outcomes. The patient appears to be suffering from meningitis caused by Staphylococcus aureus. Methicillin would be the drug of choice . It is bactericidal and unlike streptomycin and chloramphenicol it is not associated with toxicity

Positive Kernig’s and Brudzinski’s signs may indicate meningitis. While awaiting blood culture results, a broad-spectrum antibiotic such as Cefotaxime (a third generation cephalosporin) is preferred over the other medications listed.

Leiner disease belongs to a heterogeneous group of disorders associated with permanent or temporary complement C5 plasma deficiency. It is a rare disease that follows an autosomal recessive pattern of transmission. It is prevalent in female, breast-fed babies. The hallmark of this syndrome is severe diarrhoea, severe generalized seborrheic dermatitis, central nervous system defects, marked wasting, recurrent local and systemic infections, and failure to thrive.

Drug withdrawal symptoms after a period of substance abuse can lead to a range of symptoms. Amphetamines are known to cause hypersomnia, hyperphagia, and irritability, as well as vivid dreams as a result of withdrawal. Similar symptoms are found in cocaine withdrawal. Alcohol withdrawal presents with symptoms such as insomnia, tremulousness and delirium. Ecstasy withdrawal includes irritation, mood swings, fatigue and insomnia. Heroin withdrawal presents with symptoms which include dilated pupils, insomnia, abdominal cramps and muscle aches. Withdrawal from prolonged cannabis use can cause depression, anxiety restlessness and insomnia.

Leukocoria is an abnormal red reflex in which the pupil appears white. It represents various abnormalities of the visual media and is one of the primary signs of retinoblastoma. Other possible causes of leukocoria include congenital cataracts, toxocariasis, Norrie disease, retinopathy of prematurity, and Coat’s disease. Gillespie syndrome is an autosomal recessive condition characterized by congenital hypotonia, multiple ocular defects, hypoplasia of the cerebellum, and vertebral deformities. The ocular defects consist of aniridia, photophobia, reduced visual acuity, and the inability of the pupillary sphincter to contract. Leukocoria is not associated with this syndrome.

Findings described are suggestive of Waterhouse-Friderichsen syndrome which develops secondary to meningococcaemia. The reported incidence of Addison’s disease is 4 in 100,000. It affects both sexes equally and is seen in all age groups. It tends to show clinical symptoms at the time of metabolic stress or trauma. The symptoms are precipitated by acute infections, trauma, surgery or sodium loss due to excessive perspiration.

The patient’s clinical presentation is highly suggestive of Charcot–Marie–Tooth syndrome.It is a hereditary sensory and motor neuropathy. It is also the commonest cause of inherited peripheral neuropathy. The lower motor neuron signs are usually mild in childhood, the age of onset is very variable, and the distal weakness can take years to progress. It is not fatal and does not affect the normal life expectancy.

Androgen excess is one of the most common causes of advanced bone age. It usually occurs in precocious puberty or congenital adrenal hyperplasia.

Human breast milk composition is best suited to meet all the growth and development requirements of a baby. It contains numerous biochemicals ranging from macronutrients, micronutrients, minerals, immunoglobulins, inflammatory markers, and growth factors. The major bioactive factors found in human breast milk are: immunoglobulins (IgA, IgG, and IgM), cells (macrophages and stem cells), growth factors (epidermal growth factor, tumour necrosis factor-alpha, transforming growth factor-beta, and vascular endothelial growth factor), cytokines, chemokines, hormones, metabolic hormones, glycans, and mucins.

Children are able to use a palmar grasp by the age of 6 months and use a pincer grasp by the age of 9 to 10 months. They can sit with support by 6 months and sit without support by 7 to 9 months. They can vocalize by 3 months. Stranger fear appears from 7 to 10 months. So this baby’s development is normal.

Many of the symptoms favour an epilepsy diagnosis: uncontrollable jerking of the limbs and a loss of consciousness. A 24-hour EEG is used to diagnose epilepsy.

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 males is testicular enlargement, followed by growth of the penis and the scrotum at least a year after. Precocious puberty in boys in uncommon and usually has an organic cause leading to excess secretion of testosterone. These can be gonadotrophin dependent in the case of an inter cranial lesion, where the testes would be bilaterally enlarged, or from excess production from the adrenal gland in the case of adrenal hyperplasia or a tumour.

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.

One-third of patients with Guillain-Barre syndrome suffer from diaphragm weakness which can lead to further respiratory complications if there is involvement of the tongue, palate, and neck muscles. Forced vital capacity (FVC) is the best way to monitor respiratory muscle function by assessing it repeatedly. Admission for ITU is suggested when FVC is below 20ml/kg and intubation recommended when FVC is 15ml/kg or below. FVC is used in any neurological disorders wherein the respiratory muscles are affected.

Erythema nodosum (EN) is an acute, nodular, erythematous eruption that usually is limited to the extensor aspects of the lower legs. It is a delayed hypersensitivity reaction to a variety of antigens| circulating immune complexes have not been found in idiopathic or uncomplicated cases but may be demonstrated in patients with inflammatory bowel disease.Currently, the most common cause of erythema nodosum is a streptococcal infection in children and streptococcal infection and sarcoidosis in adultsIn most patients, erythema nodosum is a self-limited disease and requires only symptomatic relief using nonsteroidal anti-inflammatory drugs (NSAIDs), cool wet compresses, elevation, and bed rest.

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.

Urine culture confirms a diagnosis of a UTI. A kidney ultrasound will be the next best investigation because it will help us to visualise the bladder, kidneys, and ureters to rule out any congenital obstruction in the urinary tract that might be the actual cause of infection in this 2-month old girl.

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.

Myelomeningocele is the most common type of open neural tube defect and a serious central nervous system disorder associated with significant morbidity. It is also called open spina bifida since the dura, and arachnoid matter herniates through the defect in the vertebral column. The commonest association is the decreased folate levels during early pregnancy. The alpha-fetoprotein levels are raised in the amniotic fluid. CSF leak is a common presentation with associated macrocephaly and hydrocephaly. Prenatal surgical repair is linked to a better prognosis.

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.

Based on the presentation, she probably was administered co-amoxiclav.The liver function tests are highly suggestive of cholestatic jaundice, which is a classic adverse dug reaction related to co-amoxiclav use.Other options:- Erythromycin is more commonly associated with gastrointestinal (GI) disturbance.- Gentamicin is more commonly associated with renal impairment.- Meropenem does not commonly cause cholestasis but is associated with transaminitis.- Vancomycin is associated with red man syndrome on fast administration.

Answer: Spontaneous bacterial peritonitisThe presence of periorbital and facial oedema with normal blood pressure in this toddler indicates that he has nephrotic syndrome. Nephrotic syndrome can be associated with a series of complications that can affect an individual’s health and quality of life:Spontaneous bacterial peritonitis can develop where there is ascites present. This is a frequent development in children but very rarely found in adults.Spontaneous bacterial peritonitis (SBP) is the development of a bacterial infection in the peritoneum, despite the absence of an obvious source for the infection. It is specifically an infection of the ascitic fluid – an increased volume of peritoneal fluid. Ascites is most commonly a complication of cirrhosis of the liver. It can also occur in patients with nephrotic syndrome. SBP has a high mortality rate.The diagnosis of SBP requires paracentesis, a sampling of the peritoneal fluid taken from the peritoneal cavity. If the fluid contains large numbers of white blood cells known as neutrophils (>250 cells/µL), infection is confirmed and antibiotics will be given, without waiting for culture results. In addition to antibiotics, infusions of albumin are usually administered.Signs and symptoms of spontaneous bacterial peritonitis (SBP) include fevers, chills, nausea, vomiting, abdominal pain and tenderness, general malaise, altered mental status, and worsening ascites. Thirteen percent of patients have no signs or symptoms. In cases of acute or chronic liver failure SBP is one of the main triggers for hepatic encephalopathy, and where there is no other clear causal indication for this, SBP may be suspected.These symptoms can also be the same for a spontaneous fungal peritonitis (SFP) and therefore make a differentiation difficult. Delay of diagnosis can delay antifungal treatment and lead to a higher mortality rate.

The property described in the question is heterogeneity.Heterogeneity is when a single phenotype or genetic disorder can be caused by multiple numbers of genetic mutations.Other options:- Pleiotropy occurs when a single gene influences multiple phenotypic traits. The underlying mechanism is that the gene codes for a product that is used by various cells. A classic example of pleiotropy is the human disease PKU (phenylketonuria).- The penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms. For example, the gene responsible for a particular autosomal dominant disorder has 70% penetrance, then 70% of those with the mutation will develop the disease, while 30% will not.

The murmur and thrill indicate a right outflow tract murmur, coupled with the right ventricular heave suggests right ventricular hypertrophy. The VSD would not have been amenable to surgery due to the child’s size/weight and so instead would have been palliated with a PA band. As the child grows, this band progressively restricts pulmonary blood flow until the left to right shunt has reversed. Then it is time for the band to be removed and the VSD to be closed.Pulmonary atresia is a cyanotic condition, which may be palliated with an arterial duct stent. This answer is incorrect as the stent placement would not require a midline sternotomy and would give a continuous machinery type murmur. Pulmonary stenosis with PDA ligation is incorrect. The murmur, thrill, and heave all match a pulmonary stenosis but in the absence of an additional shunt lesion the child would not be cyanosed.

Diagnostic criteria of PCOsAccording to the American Association of Clinical Endocrinologists, at least two of three of the criteria below are required for diagnosis of PCOS after excluding other causes of irregular bleeding and elevated androgen levels.Hyperandrogenism (clinical or laboratory)Oligo- and/or anovulationPolycystic ovaries on ultrasoundDiagnosis of PCOS is possible without the presence of ovarian cysts.Rule out any other causes of hyperandrogenism and anovulation.Blood hormone levels↑ Testosterone (both total and free) or free androgen index↑ LH (LH:FSH ratio > 2:1)Oestrogen is normal or slightly elevated A clinical picture of hyperandrogenism overrules any normal hormone levels and can fulfil a diagnostic criterium of PCOS.

Prophylactic antibiotics should be given to the child to avoid infections and renal injury.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8|14). Burkitt lymphoma is a rare high-grade non-Hodgkin lymphoma endemic to west Africa and the mosquito belt. It has a close association with the contraction of Epstein-Barr virus (EBV). Burkitt lymphoma often presents with symmetrical painless lymphadenopathy, systemic B symptoms (fever, sweats, and weight loss), central nervous system involvement, and bone marrow infiltration. Classically in the textbooks, the patient also develops a large jaw tumour.Other aforementioned options are ruled out because:1. t(9|22)—Chronic myeloid leukaemia2. t(15|17)—Acute promyelocytic leukaemia3. t(14|18)—Follicular Lymphoma4. t(11|14)—Mantle Cell Lymphoma

Fanconi syndrome is a rare disorder characterized by defective proximal renal tubular reabsorption, which leads to excessive excretion of potassium, phosphate, uric acid, bicarbonates, glucose, and certain amino acids in the urine. Loss of potassium in the urine leads to hypokalaemia, while the loss of phosphate may lead to hypophosphatemic rickets. The overall impact is the failure to thrive and growth retardation.

Marfan syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, blood vessels, and heart valves. The signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression.This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.At least 25 percent of Marfan syndrome cases result from a new mutation in the FBN1 gene. These cases occur in people with no history of the disorder in their family.The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and defects in the large blood vessel that distributes blood from the heart to the rest of the body (the aorta).Associations include:Tall statureLearning disability (50%)Lens subluxation (usually upwards)Femoral herniaHemivertebraeCardiac problems (Aortic/mitral regurgitation, aneurysms)Joint hypermobilityArachnodactyly

Vitamin E deficiency in premature infants has been described as being associated with low haemoglobin levels in the 2nd month of life, haemolytic anaemia associated with thrombocytosis. Recently, low vitamin E concentrations were suspected as being associated with sudden death in infancy.

Haemolytic-uremic syndrome (HUS) is a clinical syndrome characterized by progressive renal failure that is associated with microangiopathic (nonimmune, Coombs-negative) haemolytic anaemia and thrombocytopenia. HUS is the most common cause of acute kidney injury in children. It predominantly occurs in infants and children after prodromal diarrhoea. In summer epidemics, the disease may be related to infectious causes.Bacterial infections may include the following:S dysenteriaeE ColiSalmonella typhiCampylobacter jejuniYersinia pseudotuberculosisNeisseria meningitidisS pneumoniaLegionella pneumophilaMycoplasma speciesRickettsial infections may include Rocky Mountain spotted fever and microtatobiotesViral infections may include the following:Human immunodeficiency virus (HIV)CoxsackievirusEchovirusInfluenza virusEpstein-Barr virusHerpes simplex virusFungal infections can include Aspergillus fumigatus.Vaccinations may include the following:Influenza triple-antigen vaccineTyphoid-paratyphoid A and B (TAB) vaccinePolio vaccinePregnancy-associated HUS occasionally develops as a complication of preeclampsia. Patients may progress to full-blown haemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Postpartum HUS usually occurs within 3 months of delivery. The prognosis is poor, with a 50-60% mortality rate, and residual renal dysfunction and hypertension occur in most patients.

Fanconi tubular syndrome is characterised by malabsorption of various electrolytes and substances commonly absorbed by the proximal tubule. Hypokalaemia, hypophosphatemia, and hyperchloremic metabolic acidosis is usually present. Also, urinalysis reveals an increased fractional excretion of glucose.

Point mutations are the type of mutations in which only a single nucleotide of the DNA is either deleted, substituted or a new single nucleotide is inserted into the DNA, causing alterations in the original normal DNA sequencing. The examples of point mutations include hemochromatosis, sickle cell disease, and Tay-Sach’s disease. Huntington’s disease is a trinucleotide repeat disorder. Down’s syndrome is characterized by an extra copy of chromosome 21, while Klinefelter syndrome is marked by an extra X chromosome. Fragile X syndrome is also a trinucleotide repeat disorder.

Infants may require tracheal intubation if:- direct tracheal suctioning is required- effective bag-mask ventilation cannot be provided- chest compressions are performed- endotracheal (ET) administration of medications is desired- congenital diaphragmatic hernia is suspected, or – a prolonged need for assisted ventilation exists.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder characterized by intestinal hamartomatous polyps in association with a distinct pattern of skin and mucosal macular melanin deposition (freckles on the lips, face, palms and soles). Patients with Peutz-Jeghers syndrome have an estimated 15-fold increased risk of developing intestinal cancer compared to the general population.Management: conservative unless complications develop.

CF is inherited in an autosomal recessive manner.This means that to have CF, a person must have a mutation in both copies of the CFTR gene in each cell. People with CF inherit one mutated copy of the gene from each parent, who is referred to as a carrier.CF carriers can pass their copy of the CFTR gene mutation to their children. Each time two CF carriers have a child together, the chances are: 25 percent (1 in 4) the child will have CF50 percent (1 in 2) the child will be a carrier but will not have CF25 percent (1 in 4) the child will not be a carrier of the gene and will not have CFThis male’s parents are obligate carrier because he has a sibling with CFSo the chances he is a carrier too are 2 in 3The risk of having an affected child is the chance of both himself and his partner being carriers: (2/3 × 1/25 = 2/75) × 1/4 = 1/150.

As this boy was dry for a considerable period, there is a high chance of a secondary cause for the bed wetting, such as bladder infections, constipation, diabetes, psychological stress and hormonal problems etc. These have to be excluded.

Juvenile angiofibroma (JA) is a rare benign vascular lesion of the skull base that affects young adolescent males. The management of JA is challenged by the abundant vascular blood supply of the lesion, along with the complex anatomy of the skull base and the young age of the affected population. JA typically affects the male population, most commonly between 9 and 19 years of age. The most frequent symptoms are nasal obstruction and epistaxis. Nasal obstruction may be bilateral despite the unilaterality of the lesion, due to nasopharyngeal extension as well as deviation of the nasal septum by the expansile lesion. Epistaxis is usually brisk and intermittent. Purulent nasal discharge and facial pain can be due to sinus drainage pathway obstruction, and conductive hearing loss indicates obstruction of the eustachian tube.

The physical features and developmental delay are the key aspects in the given scenario. The child in question shows features of gross motor and social developmental delay and has physical features indicative of Prader-Willi syndrome (hypopigmentation, esotropia, disproportionately small hands and feet, loss of central muscle tone and undescended testes). Children with Prader-Willi syndrome can present with failure to thrive until ,12-18 months, at which point, hyperphagia and obesity become more prominent. Other options:- Although Klinefelter syndrome can present with delayed development, undescended/small testes and reduced muscle power, the presence of small hands/feet, hypopigmentation and failure to thrive are not characteristic features. – Marfan syndrome presents with different physical features (arachnodactyly, cardio-respiratory complications and skin changes, amongst others) than those associated with Prader-Willi syndrome. – DiGeorge can manifest with developmental delay, hypotonia and feeding difficulties. However, this clinical scenario does not report any of the typical facial features, hearing abnormalities or cardiac abnormalities that are typically caused by DiGeorge syndrome. – Russell-Silver syndrome can cause developmental abnormalities, poor muscle tone and power (poor head control and muscle function), feeding difficulties and poor growth during the post-natal period and infancy. However, characteristic facial (small, triangular face, blue sclerae) and skeletal abnormalities (limb asymmetry, finger abnormalities) are not present. Therefore, Prader-Willi syndrome is the most appropriate diagnosis for this patient.Note:Prader-Willi syndrome is an example of genetic imprinting where the phenotype depends on whether the deletion occurs on a gene inherited from the mother or father: In Prader-Willi syndrome, it is the paternal gene that is deleted from the long arm of chromosome 15, while in Angelman syndrome the maternal gene is deleted. Prader-Willi syndrome can occur due to the microdeletion of paternal 15q11-13 (70% of cases) maternal uniparental disomy of chromosome 15.

Pale stools suggest obstructive jaundice. Initially, the symptoms of biliary atresia are indistinguishable from those of neonatal jaundice, a usually harmless condition commonly seen in infants. However, infants with biliary atresia develop progressive conjugated jaundice, pale white stools and dark urine.

Unprotected anal or vaginal sexual intercourse with an infected individual is by far the most common (95%) route by which HIV is transmitted. Other options:- Blood transfusion is an extremely rare cause of HIV transmission in the UK. – While HIV can be transmitted from mother to baby either during birth or via breastfeeding, the transmission rate is only 5 – 20%.- Sharing contaminated needles does put individuals at risk of getting HIV, although public health measures are in place to reduce this risk. – Although HIV can be transmitted via this route, it is around ten times less likely to result in transmission than unprotected anal or vaginal intercourse with an infected individual.

Dandy-Walker syndrome is characterised by symptoms of brain maldevelopment that are seen in this patient. A large cranium indicates hydrocephalus, and the hypotonia indicates poor limb development.

From the options mentioned here, the closest diagnosis is haemophilia. This is a mixed picture, as a purpuric rash on the buttocks does not correlate with this diagnosis. However, the most appropriate diagnosis is haemophilia.

Milestones of 6 monthsSocial and EmotionalKnows familiar faces and begins to know if someone is a stranger Likes to play with others, especially parents Responds to other people’s emotions and often seems happy Likes to look at self in a mirror Language/CommunicationResponds to sounds by making sounds Strings vowels together when babbling (“ah,” “eh,” “oh”) and likes taking turns with the parent while making sounds Responds to own name Makes sounds to show joy and displeasure Begins to say consonant sounds (jabbering with “m,” “b”) Cognitive (learning, thinking, problem-solving)Looks around at things nearby Brings things to mouth Shows curiosity about things and tries to get things that are out of reach Begins to pass things from one hand to the other Movement/Physical DevelopmentRolls over in both directions (front to back, back to front) Begins to sit without support When standing, supports weight on legs and might bounce Rocks back and forth, sometimes crawling backwards before moving forward

In secretory OM, effusion in the middle ear is present which does not produce any pain to the patient in comparison to acute OM which produces otalgia. The family members are the ones to notice hearing loss as the patient usually is not aware of it. On otoscopy, the features described in the question are prominent. Otitis externa is usually painful and it also produces an itching sensation. Chronic otitis media is painful and may interfere with balance problems. Cholesteatoma is an abnormal cystic growth in the middle ear that usually discharges foul-smelling fluids and as it grows, otalgia can appear.

Septic (infectious) arthritis is a bacterial infection of the joint space. Contamination occurs either via the bloodstream, iatrogenically, or by local extension (e.g., penetrating trauma). Patients with damaged (e.g., patients with rheumatoid arthritis) or prosthetic joints have an increased risk. Patients usually present with an acutely swollen, painful joint, limited range of motion, and a fever. Suspected infectious arthritis requires prompt arthrocentesis for diagnosis. In addition to the immediate broad-spectrum antibiotic therapy, surgical drainage and debridement may be necessary to prevent cartilage destruction and sepsis.

Chédiak–Higashi syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

The clinical picture suggests intracranial haemorrhage which is uncommon but prevalent in pre-term babies. The rest of the options suggest peripheral causes which do not affect the central function.

Acute lymphoblastic leukaemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, frequent infections with fever as well as anaemia with thrombocytopenia. As an acute leukaemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. The patient’s age also favours the diagnosis of ALL as it occurs most commonly in children, particularly those between the ages of two and five.

Café-au-lait spots is hyperpigmented lesions that vary in colour from light brown to dark brown, with borders that may be smooth or irregular. Causes include:
Neurofibromatosis type I
McCune–Albright syndrome
Legius syndrome
Tuberous sclerosis
Fanconi anaemia
Idiopathic
Ataxia-telangiectasia
Basal cell nevus syndrome
Benign congenital skin lesion
Bloom syndrome
Chediak-Higashi syndrome
Congenital nevus
Gaucher disease
Hunter syndrome
Maffucci syndrome
Multiple mucosal neuroma syndrome
Noonan syndrome
Pulmonary Stenosis
Silver–Russell syndrome
Watson syndrome
Wiskott–Aldrich syndrome

The diagnosis of scabies can often be made clinically in patients with a pruritic rash and characteristic linear burrows. Definitive testing relies on the identification of mites or their eggs, eggshell fragments, or scybala. This is best undertaken by placing a drop of mineral oil directly over the burrow on the skin and then superficially scraping longitudinally and laterally across the skin with a scalpel blade. (Avoid causing bleeding.) Scraping 15 or more burrows often produces only 1 or 2 eggs or mites, except in a case of crusted scabies, in which many mites will be present. The sample is placed on a microscope slide and examined under low and high power. Potassium hydroxide should not be used, since it can dissolve mite pellets. Failure to find mites is common and does not rule out the diagnosis of scabies.

A minority of affected individuals may experience severe liver failure. This happens most frequently in people with Wilson’s disease during adolescence and more commonly in women. These individuals may rapidly develop signs and symptoms of liver disease, often associated with anaemia due to breakdown of red blood cells (haemolysis) and mental confusion. In some patients, liver disease does not reveal itself, and the patient develops neurologic (brain-related) symptoms. Common neurological symptoms of Wilson disease that may appear and progress with time include tremor, involuntary movements, difficulty swallowing (dysphagia), difficulty speaking and poor articulation (dysarthria), lack of coordination, spasticity, dystonic postures, and muscle rigidity. Almost all affected individuals with the neurological symptoms of Wilson’s disease have Kayser-Fleischer rings in their eyes that can be identified by a slit lamp examination.

When a child does not hear the sound in the middle during Weber test, it means they either they have a conductive hearing loss on the side they hear the sound, or a sensorineural hearing loss on the opposite side. Rinne’s test helps distinguish between the two. In this particular case, the hearing loss is most probably conductive due to the middle ear effusion. Therefore, Weber’s test should be localised to the left and Rinne’s should be positive on the right.

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.

The most probable diagnosis based on the clinical presentation is myocarditis secondary to Coxsackie virus infection.Myocarditis is an important cause of acquired heart failure. The other infective causes of myocarditis are influenza and adenoviruses, and bacterial causes as seen with Borrelia burgdorferi (Lyme disease). Rheumatic fever is unlikely if the ASO titres are within normal limits. While pancarditis may occur as part of Kawasaki disease| the patient is unlikely to present in failure.

The child has a history of pharyngitis followed 10 days later by signs of glomerulonephritis. In this particular case, it is most probably a post-streptococcus glomerulonephritis which accounts for 80% of paediatric cases of glomerulonephritis.

A ventricular septal defect (VSD) is a common form of congenital heart defects and is characterised by the presence of a hole in the wall that separates the right from the left ventricle. Medium or large defects can cause many complications. One of these complication is Eisenmenger syndrome, characterised by reversal of the shunt (from left-to-right shunt into a right-to-left) ,cyanosis and pulmonary hypertension.

Certain infections and medications cause characteristic skin lesions, which are the result of hypersensitivity reactions to these agents. A skin rash characterized by the eruption of macules, papules, and target-like circular lesions is referred to as erythema multiforme. The target or iris lesions appear rounded with a red centre surrounded by a pale ring, which in turn is surrounded by a dark red outer ring. These are acute and self-limiting with a propensity for distal extremities. The most common infectious cause is the infection with herpes simplex virus 1 and 2 to a lesser extent. Other notable infectious causes of erythema multiforme include Mycoplasma pneumoniae, cytomegalovirus, HIV, hepatitis c virus, varicella zoster virus, adenovirus, and some fungal infections. Norovirus infection has not been implicated in the aetiology of erythema multiforme.

Minimal-change disease (MCD) refers to a histopathologic glomerular lesion, typically found in children, that is almost always associated with nephrotic syndrome. The most noticeable symptom of MCD is oedema, which can develop very rapidly. Due to the renal loss of proteins muscle wasting and growth failure may be seen in children. Renal function is usually not affected and a proteinuria of more than 40 mg/h/m2 is the only abnormal finding in urinalysis.

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.

Hyperkalaemia is not to evaluate or detect AKI but rather the result of it. If one of the rest of the options is present, then AKI would be suspected.

Immunoglobulin G (IgG) glomerular immune deposits are seen more commonly in HSP compared to IgA nephropathy.The presentation of the child is highly suggestive of Henoch-Schönlein purpura (HSP). It is an IgA-mediated, autoimmune hypersensitivity vasculitis that targets the small vessels of the skin, GI tract, kidneys, and joints.It is most commonly seen in children aged 3 – 6years and is twice as common in boys than girls. Preceding viral URTI with low-grade pyrexia is common. The most common organism associated with HSP is, however, Group A streptococcal infection A.A purpuric rash is seen on the back of the legs and buttocks and can less frequently, affect the arms. Arthralgia is common (usually knees/ankles) in these patients. Abdominal pain and bloody diarrhoea may occur. And half of the children with HSP have renal involvement. Rarely, it can lead to end-stage renal failure.Treatment includes adequate hydration, occasionally steroids, and other immunosuppressants. The disease can recur in 1 in 3 children.

Cranial nerve II (CN II or optic nerve) runs along the midline of the ventral surface of the brain and conveys visual information from the retina of each eye to the corresponding region of the primary visual cortex. The right half of the visual field of both eyes is processed by the left half of the retina, while the right half of the retina processes the left half of the visual field. These retinal ganglion cells project myelinated axons, carrying CN II sensory afferent fibres, through the optic chiasm, where optic nerve fibres from the nasal half of each retina decussate to the contralateral side of the brain for processing. After passing through the optic chiasm, the optic nerve becomes the optic tract that synapses to the lateral geniculate nucleus (LGN) of the thalamus and subsequently projects optic radiations to the primary visual cortex (V1) of the occipital lobe. The optic tract also projects to the superior colliculus, pretectal nuclei, and suprachiasmatic nuclei. This part of the optic pathway serves the important light reflex.Due to the anatomical location of the optic chiasm superior to the pituitary gland, a suprasellar extension of a pituitary macroadenoma will lead to compression of the optic nerve fibres decussating at the optic chiasm. Impingement of these nerves prevents visual information from the temporal visual fields of each eye from reaching the processing centres in the brain, leading to peripheral vision loss

The likely diagnosis in this case is Haemolytic Uremic Syndrome (HUS), which is generally seen in young children presenting with a triad of symptoms, namely: acute renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. The typical cause of HUS is ingestion of a strain of Escherichia coli causing diarrhoea in these cases as well.

Minimal change glomerulonephritis presents with mild or benign urinalysis findings. However, proteinuria together with the presence of oval fat bodies are typical.Minimal change glomerulonephritis (nephropathy) accounts for most cases of childhood nephrotic syndrome and 20–25% of adult nephrotic syndrome.

The swelling and bruising on the mandible needs to be checked for fractures. A facial X-ray can adequately visualize this.

Boys and men with Klinefelter syndrome typically have small testes that produce a reduced amount of testosterone (primary testicular insufficiency). Testosterone is the hormone that directs male sexual development before birth and during puberty. Without treatment, the shortage of testosterone can lead to delayed or incomplete puberty, breast enlargement (gynecomastia), decreased muscle mass, decreased bone density, and a reduced amount of facial and body hair. As a result of the small testes and decreased hormone production, affected males are not generally infertile but may benefit from assisted reproductive technologies. Some affected individuals also have differences in their genitalia, including undescended testes (cryptorchidism), the opening of the urethra on the underside of the penis (hypospadias), or an unusually small penis (micropenis).

Perthes’ disease is a disease of the hip in children. It presents with pain that is typically located in the groin area. The pain is often present only during physical activity. Most children seek medical attention because of limping.

Osgood–Schlatter disease is pain caused by inflammation of the patella tendon at the tibial insertion.

Slipped upper femoral epiphysis occurs classically in adolescence (M:F = 3:2)

Types of DNA mutations and their impactpoint mutation:Substitution: One base is incorrectly added during replication and replaces the pair in the corresponding position on the complementary strand as in Sickle cell anaemiaInsertion: One or more extra nucleotides are inserted into replicating DNA, often resulting in a frameshift as in one form of beta-thalassemiaDeletion: One or more nucleotides is skipped during replication or otherwise excised, often resulting in a frameshift as in Cystic fibrosis.Chromosomal mutation:Inversion: One region of a chromosome is flipped and reinserted as in Opitz-Kaveggia syndromeDeletion: A region of a chromosome is lost, resulting in the absence of all the genes in that area as in Cri du chat syndromeDuplication: A region of a chromosome is repeated, resulting in an increase in dosage from the genes in that region as in some cancers and Charcot-Marie toothTranslocation: A region from one chromosome is aberrantly attached to another chromosome as in One form of leukaemiaCopy number variation:Gene amplification: The number of tandem copies of a locus is increased as in Some breast cancersExpanding trinucleotide repeat: The normal number of repeated trinucleotide sequences is expanded as in Fragile X syndrome, Huntington’s disease