The Kaplan–Meier estimator, also known as the product limit estimator, is a non-parametric statistic used to estimate the survival function from lifetime data. In medical research, it is often used to measure the fraction of patients living for a certain amount of time after treatment.

Tetralogy of Fallot (TOF), a congenital heart defect, includes the following: right ventricular hypertrophy, ventricular septal defect, abnormal position of the aorta and pulmonary valve stenosis. The O2 saturation in patients with TOF is typically lower than normal and the condition usually becomes symptomatic early in life. A feature of the disease with high diagnostic significance is squatting or crouching of the infant as a compensatory mechanism to increase the peripheral vascular resistance.

The nerve supply to the tensor tympani is the mandibular nerve.The mandibular nerve is the only division of the trigeminal nerve that carries motor fibres.Tensor tympani is a muscle that lies in a bony canal just superior to the pharyngotympanic tube. It originates from the cartilaginous portion of the pharyngotympanic tube, the bony canal in which it sits, and the greater wing of the sphenoid bone. It inserts into the upper part of the handle of the malleus. When contracted, it pulls the handle of the malleus medially. This action increases the tension across the tympanic membrane, reducing the magnitude of vibrations transmitted into the middle ear. This dampens loud noises or noises produced by chewing. Tensor tympani is innervated through the nerve to tensor tympani, which arises from the mandibular nerve.Other options:- The vestibulocochlear nerve is the eighth cranial nerve. This nerve has two components, a vestibular division that carries balance information, and a cochlear division that carries hearing information.- The glossopharyngeal nerve is the ninth cranial nerve. It has a wide range of functions. It carries taste and sensation from the posterior third of the tongue, as well as sensation from the pharyngeal wall and tonsils, the middle ear, external auditory canal and auricle. It carries parasympathetic fibres that supply the parotid gland. It also supplies the baroreceptors and chemoreceptors of the carotid sinus and supplies the secretomotor fibres to the parotid gland.- The maxillary nerve carries only sensory fibres.- The facial nerve is the seventh cranial nerve. It supplies the muscles of facial expression, as well as stylohyoid, the posterior belly of digastric, and stapedius (the only other muscle associated with the middle ear). It carries taste from the anterior two-thirds of the tongue and sensation from part of the external acoustic meatus, parts of the auricle and the retro-auricular area. It provides secretomotor fibres which supply to the submandibular gland, sublingual gland (via chorda tympani nerve), nasal glands and lacrimal glands.

Gait variations in children are usually physiologically normal and only become a cause of concern when they persist or are associated with pain or other medical symptoms. Genu varus, also known as knock knees causes an outward rotation of the leg, leading the toes pointing outwards. The condition usually resolves by the age of 18 months. In comparison, in- toeing occurs with genu varus. Metatarsus adductus is also associated with an inward pointing of the toes.

Maternal and fetal toxoplasma infection may be avoided by advising pregnant women to wear gloves when gardening or handling cat litter and to cook meat thoroughly. Affected babies are treated with pyrimethamine, sulfadiazine, and folic acid.

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.

Answer: MittelschmerzMittelschmerz is midcycle abdominal pain due to leakage of prostaglandin-containing follicular fluid at the time of ovulation. It is self-limited, and a theoretical concern is treatment of pain with prostaglandin synthetase inhibitors, which could prevent ovulation. The pain of mittelschmerz usually occurs in the lower abdomen and pelvis, either in the middle or to one side. The pain can range from a mild twinge to severe discomfort and usually lasts from minutes to hours. In some cases, a small amount of vaginal bleeding or discharge might occur. Some women have nausea, especially if the pain is very strong.Diagnosis of pelvic pain in women can be challenging because many symptoms and signs are insensitive and nonspecific. As the first priority, urgent life-threatening conditions (e.g., ectopic pregnancy, appendicitis, ruptured ovarian cyst) and fertility-threatening conditions (e.g., pelvic inflammatory disease, ovarian torsion) must be considered. Many women never have pain at ovulation. Some women, however, have mid-cycle pain every month, and can tell by the pain that they are ovulating.As an egg develops in the ovary, it is surrounded by follicular fluid. During ovulation, the egg and the fluid, as well as some blood, are released from the ovary. While the exact cause of mittelschmerz is not known, it is believed to be caused by the normal enlargement of the egg in the ovary just before ovulation. Also, the pain could be caused by the normal bleeding that comes with ovulation.Pelvic inflammatory disease can be ruled out if the patient is not sexually active.

The patient has hyperprolactinaemia with otherwise normal oestradiol, FSH and LH. This is highly suggestive of Prolactinoma rather than a non functioning tumour.In polycystic ovaries, there is increase in the level of LH while FSH is normal or low.

Congenital heart diseases such as complete atrioventricular septal defects are most likely to cause large left to right shunts leading to faltering growth due to chronic severe hypoxia, pulmonary oedema, and feeding problems. Isolated atrial septal defects or ventricular septal defects result in relatively smaller shunts. Pulmonary stenosis and bicuspid aortic valve do not cause chronic systemic hypoxia. People with these conditions are often asymptomatic and only show some symptoms with intense physical activity.

Sepsis can be described as a condition in which there is a dysregulated inflammatory response to an infection. In the case of neonates, sepsis can be life threatening and may present with respiratory distress more than 4 hours after birth, shock, seizures, and multi organ failure. Risk factors that further point to sepsis include prolonged rupture of maternal membranes for more than 24 hours before birth, a history of a maternal fever during labour, or parenteral antibiotic treatment given to the mother for a suspected or confirmed bacterial infection.

Pityriasis rosea is a common, acute exanthem of uncertain aetiology. Viral and bacterial causes have been sought, but convincing answers have not yet been found. Pityriasis rosea typically affects children and young adults. It is characterized by an initial herald patch, followed by the development of a diffuse papulosquamous rash. The herald patch often is misdiagnosed as eczema. Pityriasis rosea is difficult to identify until the appearance of characteristic smaller secondary lesions that follow Langer’s lines (cleavage lines). Several medications can cause a rash similar to pityriasis rosea, and several diseases, including secondary syphilis, are included in the differential diagnosis.

Linear regression is a basic and commonly used type of predictive analysis. The overall idea of regression is to examine two things: (1) do a set of predictor variables do a good job in predicting an outcome (dependent) variable? (2) Which variables, in particular, are significant predictors of the outcome variable, and in what way do they–indicated by the magnitude and sign of the beta estimates–impact the outcome variable.These regression estimates are used to explain the relationship between one dependent variable and one or more independent variables. Three major uses for regression analysis are (1) determining the strength of predictors, (2) forecasting an effect, and (3) trend forecasting

Inhaled objects are more likely to enter the right lung for several reasons. First the right bronchus is shorter, wider and more vertical than the left bronchus. Also, the carina (a ridge-like structure at the point of tracheal bifurcation) is set a little towards the left. The terminal bronchiole is a very small space and impossible for the seed to lodge here.

Oligomenorrhoea and BMI of 40.4 is suggestive of Polycystic ovary syndrome (PCOS). To diagnose PCOS 2 out of following 3 criteria should be present : oligo/anovulation, hyperandrogenism, clinical (hirsutism or less commonly male pattern alopecia) or biochemical (raised FAI or free testosterone) and polycystic ovaries on ultrasound.

Answer: The burn area is extremely painful until skin graftedThird-degree burns destroy the epidermis and dermis. Third-degree burns may also damage the underlying bones, muscles, and tendons. The burn site appears white or charred. There is no sensation in the area since the nerve endings are destroyed. These are not normally painful until after skin grafting is done since the nerve endings have been destroyed.

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.

The type of significance test used depends on whether the data is parametric (can be measured, usually normally distributed) or non-parametric.
Parametric tests:
Student’s t-test – paired or unpaired*
Pearson’s product-moment coefficient – correlation

Non-parametric tests:
Mann-Whitney U test – unpaired data
Wilcoxon signed-rank test – compares two sets of observations on a single sample
chi-squared test – used to compare proportions or percentages
Spearman, Kendall rank – correlation.

The outcome measured is not normally distributed, i.e. it is non-parametric. This excludes the Student’s t-tests. We are not comparing percentages/proportions so the chi-squared test is excluded. The Mann–Whitney U test is a nonparametric test of the null hypothesis that it is equally likely that a randomly selected value from one sample will be less than or greater than a randomly selected value from a second sample.
This test can be used to investigate whether two independent samples were selected from populations having the same distribution.

Haematuria and abdominal swelling may indicate either polycystic kidney disease or a tumour. Because of the patient’s age, the likelihood of a tumorous growth is small, thus an ultrasound is the best choice for this case.

A teratoma is a tumour containing tissue elements that are similar to normal derivatives of more than one germ layer. They usually contain skin, hair, teeth and bone tissue and are more common in children, behaving as a benign tumour. After puberty, they are regarded as malignant and can metastasise.

Erythema multiforme lesions typically heal without scarring. Other options:- In erythema multiforme, lesions are typically symmetrical and acral, i.e. on the hands, feet and limbs. – HSV is a common cause of erythema multiforme in children, accounting for at least 50% of cases| the lesions typically have damaged skin in the centre and are dusky and bullous (in contrast to urticaria, where the centre of the lesion is normal).

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.

Hyperkinetic Gait is seen with certain basal ganglia disorders including Sydenham’s chorea, Huntington’s Disease and other forms of chorea, athetosis or dystonia. The patient will display irregular, jerky, involuntary movements in all extremities. Walking may accentuate their baseline movement disorder.

Juvenile myoclonic epilepsy is an epilepsy syndrome characterized by myoclonic jerks, generalized tonic-clonic seizures (GTCSs), and sometimes, absence seizures. The seizures of juvenile myoclonic epilepsy often occur when people first awaken in the morning. Seizures can be triggered by lack of sleep, extreme fatigue, stress, or alcohol consumption. Onset typically occurs around adolescence in otherwise healthy children. The causes of juvenile myoclonic epilepsy are very complex and not completely understood. Mutations in one of several genes, including the GABRA1 and the EFHC1 genes, can cause or increase susceptibility to this condition. Although patients usually require lifelong treatment with anticonvulsants, their overall prognosis is generally good.

Sturge-Weber syndrome (SWS), also called encephalotrigeminal angiomatosis, is a neurocutaneous disorder with angiomas that involve the leptomeninges (leptomeningeal angiomas [LAs]) and the skin of the face, typically in the ophthalmic (V1) and maxillary (V2) distributions of the trigeminal nerve. The hallmark of SWS is a facial cutaneous venous dilation, also referred to as a nevus flammeus or port-wine stain (PWS).Signs and symptoms:SWS is generally diagnosed clinically, based on the typical cutaneous, central nervous system (CNS), and ocular abnormalities associated with it.Neurological signs include the following:Developmental delay/intellectual disabilityLearning problemsAttention deficit-hyperactivity disorderInitial focal seizures progressing to frequent, secondarily generalized seizuresIncreasing seizure frequency and duration despite the use of antiepileptic drugs (AEDs)Increasing duration of a transient postictal deficitIncrease in focal or diffuse atrophy – Determined by serial neuroimagingProgressive increase in calcificationsDevelopment of hemiparesisDeterioration in cognitive functioningPhysical signs of SWS are as follows:Port-wine stainMacrocephalyOcular manifestationsSoft-tissue hypertrophyHemiparesisVisual lossHemianopsiaOcular involvement in SWS may include the following signs:BuphthalmosGlaucomaTomato-catsup colour of the fundus (ipsilateral to the nevus flammeus) with glaucomaConjunctival and episcleral haemangiomasDiffuse choroidal haemangiomasHeterochromia of the iridesTortuous retinal vessels with occasional arteriovenous communications

A 10 year old child, with a history of URTI and haematuria, presents a picture consistent with a diagnosis of IgA nephropathy. This condition can present with proteinuria and generalized swelling. However, an important differentiating point from rapidly progressive GN is the duration. IgA nephropathy is usually <10 days (commonly 4-5 day history of infection).

Answer: Inflammatory bowel diseaseThe inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn disease, are chronic inflammatory disorders of the gastrointestinal tract most often diagnosed in adolescence and young adulthood, with a rising incidence in paediatric populations. Inflammatory bowel disease is caused by a dysregulated mucosal immune response to the intestinal microflora in genetically predisposed hosts. Although children can present with the classic symptoms of weight loss, abdominal pain, and bloody diarrhoea, many present with nonclassical symptoms of isolated poor growth, anaemia, or other extraintestinal manifestations.Colorectal Carcinoma (CRC) is rare in patients less than 20 years of age.

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.

Hirschsprung’s disease is characterized by congenital absence of the autonomic plexus (Meissner’s and Auerbach’s plexus) in the intestinal wall. Usually limited to the distal colon, it can occasionally involve the entire colon or even the small bowel. There is abnormal or absent peristalsis in the affected segment, resulting in continuous spasm of smooth muscle and partial/complete obstruction. This causes accumulation of intestinal contents and dilatation of proximal segment. Skip lesions are highly uncommon. This disease is seen early in life with 15% patients presenting in first month, 60% by 1 year of age and 85% by the age of 4 years. Symptoms include severe and complete constipation, abdominal distension and vomiting. Patients with involvement of ultra-short segments might have mild constipation with intervening diarrhoea. In older children, symptoms include failure to thrive, anorexia, and lack of an urge to defecate. On examination, an empty rectum is revealed with stool palpable high up in the colon. If not diagnosed in time, it can lead to Hirschsprung’s enterocolitis (toxic megacolon), which can be fulminant and lead to death. Diagnosis involves a barium enema or a rectal suction biopsy. Barium enema shows a transition in diameter between the dilated, normal colon proximal to the narrowed, affected distal segment. It is to be noted that barium enema should be done without prior preparation, which can dilate the abnormal segment, leading to a false-negative result. A 24-hour post-evacuation film can be obtained in the neonatal period – if the colon is still filled with barium, there is a high likelihood of Hirschsprung’s disease. Full-thickness rectal biopsy is diagnostic by showing the absence of ganglion cells. Acetylcholinesterase staining can be done to highlight the enlarged nerve trunks. Abnormal innervation can also be demonstrated by rectal manometry.

Somogyi effect presents with night-time hypoglycaemia followed by early-morning hyperglycaemia, hence the glycosuria.

Advanced paternal age is associated with poor quality sperm leading to a reduction in overall fertility along with an increase in the occurrence of various medical disorders in the fetus. Advanced paternal age has been implicated as a risk factor for diseases like retinoblastoma, Marfan’s syndrome, neurofibromatosis, achondroplasia, autism spectrum disorders, schizophrenia, and acute lymphoblastic leukaemia. Down’s syndrome is mostly considered a consequence of advanced maternal age, but advanced paternal age has also been implicated as a risk factor. Turner syndrome is not found to be caused by advanced paternal age.

While the clinical scenario and the anosmic presentation of the child are highly suggestive of Kallmann’s syndrome, reduced testosterone, FSH and LH levels can confirm the diagnosis.Kallman’s syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallman’s syndrome is thought to be caused by a failure of GnRH-secreting neurons to migrate to the hypothalamus.Clinical features of Kallmann’s syndrome include:- Delayed puberty- Hypogonadism, cryptorchidism- Anosmia- Low sex hormone levels – Inappropriately low/normal LH and FSH levels- Some patients can present with associated cleft lip/palate and visual/hearing defects.

In the case of anterior nasal bleeds, when the bleeding point is clearly visualised the best management step is cautery, either electrical or chemical.

An appendicular mass, on the whole, is managed medically with intravenous antibiotics and monitoring for signs of obstruction or on-going sepsis. If the child is not responding to medical management, then surgery is performed. This is due to the high morbidity risk associated with operating on an appendicular mass. Consent for a limited right hemi-colectomy must be taken after explaining the increased risk of complications. The decision whether or not to perform an interval appendicectomy is controversial and currently subject to a multicentre national trial. The likelihood of another episode of appendicitis is 1 in 5. Other options:- Ultrasound and clinical examination is sufficient to confirm the diagnosis, especially in a boy. This may not be the case in females.- Majority of appendicular masses respond to conservative management. – Raised CRP indicates significant inflammatory response and thus intravenous antibiotics are indicated. – Intravenous antibiotics are indicated due to sepsis. Oral antibiotics are not sufficient to tackle sepsis in this scenario.

This girl most likely has Turner syndrome (TS) also known as 45,X, a condition in which a female is partly or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hairline at the back of the neck, short stature, and swollen hands and feet are seen at birth. Typically, they are without menstrual periods, do not develop breasts, and are unable to have children. Heart defects, diabetes, and low thyroid hormone occur more frequently. Most people with TS have normal intelligence. Many, however, have troubles with spatial visualization such as that needed for mathematics. Vision and hearing problems occur more often. Turner syndrome is not usually inherited from a person’s parents. No environmental risks are known and the mother’s age does not play a role. As a chromosomal condition, there is no cure for Turner syndrome. However, much can be done to minimize the symptoms including prescribing growth hormone, either alone or with a low dose of androgen, and oestrogen replacement therapy which is crucial long term for maintaining good bone integrity, cardiovascular health and tissue health

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.

Developmental milestones at 4 months of age:Social and Emotional:Smiles spontaneously, especially at people Likes to play with people and might cry when playing stops Copies some movements and facial expressions, like smiling or frowningLanguage/CommunicationBegins to babble Babbles with expression and copies sounds he hears Cries in different ways to show hunger, pain, or being tiredCognitive (learning, thinking, problem-solving)Lets you know if he is happy or sad Responds to affectionReaches for a toy with one hand Uses hands and eyes together, such as seeing a toy and reaching for it Follows moving things with eyes from side to side Watches faces closely Recognizes familiar people and things at a distance Movement/Physical DevelopmentHolds head steady, unsupported Pushes down on legs when feet are on a hard surface May be able to roll over from tummy to back Can hold a toy and shake it and swing at dangling toys Brings hands to mouth When lying on stomach, pushes up to elbows

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.

Patent ductus arteriosus is a heart defect that occurs in around 50% of the preterm or low birth weight infants. It is characterized by the failure of the fetal ductus arteriosus to close after birth. There are certain risk factors which predispose an infant to a patent ductus arteriosus. The most important risk factor is trisomy 21 or Down’s syndrome, which is associated with multiple cardiac defects. Other factors are congenital rubella syndrome, birth at high altitudes, and female gender.

The most probable diagnosis for this patient would be Kawasaki disease.Kawasaki disease:It is an acute systemic disorder of childhood that predominantly occurs in Japan (800 cases per million in children under the age of 5 years). The causative factor is not known, but mycoplasma and HIV infection may be associated in some cases. Clinical Features:The principal clinical features are fever persisting for more than five days, bilateral non-purulent conjunctival congestion, cervical lymphadenopathy, polymorphous rash, arthralgia, palmar erythema and strawberry tongue. Other options:- Diffuse cutaneous systemic sclerosis is associated with skin, renal and gut involvement. Arthralgia, morning stiffness and flexor tenosynovitis are common. – Behçet syndrome is a vasculitis of unknown aetiology that characteristically targets venules. – Felty syndrome is the association of splenomegaly and neutropenia with rheumatoid arthritis. Lymphadenopathy is common, and there is a predisposition to recurrent infections.

A consultation with an ENT is required to establish the reason for the child’s drooling and stridor indicating and obstructive process. Enlarged tonsils and adenoids should be checked.

The murmur of tricuspid valve regurgitation is typically a high-pitched, blowing, holosystolic, plateau, nonradiating murmur best heard at the lower left sternal border. The intensity is variable, but tends to increase during inspiration (Carvallo’s sign), with passive leg raising, after a post-extrasystole pause, and following amyl nitrite inhalation. The intensity of the murmur tends to correlate positively with the severity of regurgitation. Right ventricular enlargement may displace the location of the murmur leftward. Right ventricular failure may abolish respiratory variation. When tricuspid regurgitation is caused by pulmonary hypertension, a pulmonic ejection click may be audible. Severe tricuspid regurgitation is commonly accompanied by a third heart sound emanating from the right ventricle and best heard at the lower left sternal border. Severe tricuspid regurgitation typically produces an accentuated jugular cv wave and may produce hepatic congestion with a pulsatile liver.The auscultatory findings associated with ventricular septal defect are variable, depending on a variety of morphologic and hemodynamic considerations. The systolic murmur associated with a Roger’s-type ventricular septal defect (regurgitant jet flows directly into the right ventricular outflow tract) in patients with low pulmonary vascular resistance is a low to medium pitched, holosystolic murmur with midsystolic accentuation. The intensity of the murmur is typically grade 3 or higher.Patent ductus arteriosus produces a continuous murmur in patients with normal pulmonary vascular resistance.

Cot death also know as SIDS or Sudden Infant Death syndrome. Putting a baby to sleep on his back has been shown to reduce the risk of SIDS.

Prednisone is used for the treatment of myasthenia gravis if there is no initial response to the anticholinesterase medications. Pyridostigmine can make the symptoms of myasthenia gravis worse if used  in the initial stages of treatment. 

The most probable diagnosis for the patient would be DiGeorge syndrome due to 22q11 deletion. It causes embryonic defects of the third and fourth branchial arches. It is sporadic in 90% of cases and 10 % inherited from parents as autosomal dominant.Characterised by distinct facial features (micrognathia, cleft palate, short philtrum, and low-set ears), hypocalcaemia, mental retardation, cardiac defects (especially tetralogy of Fallot), and immune deficiencies.A useful memory aid is CATCH-22:- Cardiac defects- Abnormal facial features- Thymic aplasia/hypoplasia- Cleft palate- Hypocalcaemia/Hypoparathyroidism- 22 – Due to 22q11 deletion

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.

Crigler-Najjar syndrome is a rare genetic disorder characterized by an inability to properly convert and clear bilirubin from the body.The hallmark finding of Crigler-Najjar syndrome is a persistent yellowing of the skin, mucous membranes and whites of the eyes (jaundice).There are two forms of this disorder: Crigler-Najjar syndrome type I, characterized by a nearly complete lack of enzyme activity and severe, even life-threatening symptoms| and Crigler-Najjar syndrome type II, characterized by partial enzyme activity and milder symptoms. Both forms are inherited as autosomal recessive traits and are caused by errors or disruptions (mutations) of the UGT1A1 gene.The symptoms of Crigler-Najjar syndrome type I become apparent shortly after birth. Affected infants develop severe, persistent yellowing of the skin, mucous membranes and whites of the eyes (jaundice). These symptoms persist after the first three weeks of life.Infants are at risk for developing kernicterus, also known as bilirubin encephalopathy, within the first month of life.Crigler-Najjar syndrome type II is a milder disorder than type I. Affected infants develop jaundice, which increases during times when an infant is sick (concurrent illness), has not eaten for an extended period (prolonged fasting) or is under general anaesthesia. Some people have not been diagnosed until they are adults. Kernicterus is rare in Crigler-Najjar syndrome type II, but can occur especially when an affected individual is sick, not eating or under anaesthesia

Answer: LaparoscopyThe diagnostic accuracy of laparoscopy for impalpable testis is well recognized. Approximately 20% of undescended testes are truly impalpable, and laparoscopy is actually regarded as the gold standard for their localization| none of the currently available imaging techniques (ultrasound, computerized tomography, or magnetic resonance imaging) has proven to be 100% reliable in predicting the presence or absence of a testis.In this respect, not only can laparoscopy be considered the most reliable tool to provide information on the location of the testis but also to confirm its absence.Undescended testes in boys is a very common congenital abnormality in which one or both testes does not reach the bottom of the scrotum prior to birth. The incidence of the condition is 3–5% among all boys at birth, and decreases to 0.8–1% after 6 months of age.Males with undescended testes have a lower sperm count, poorer quality sperm, and lower fertility rate, compared to males whose testicles descend normally| the rate of subfertility increases with bilateral involvement and increasing age at the time of orchidopexy.

Answer: Undertake a laparotomyIntussusception, which is defined as the telescoping or invagination of a proximal portion of intestine (intussusceptum) into a more distal portion (intussuscipiens), is one of the most common causes of bowel obstruction in infants and toddlers.Intussusception may be ileoileal, colocolic, ileoileocolic, or ileocolic (the most common type).Most infants with intussusception have a history of intermittent severe cramping or colicky abdominal pain, occurring every 5-30 minutes. During these attacks, the infant screams and flexes at the waist, draws the legs up to the abdomen, and may appear pale. These episodes may last for only a few seconds and are separated by periods of calm normal appearance and activity. However, some infants become quite lethargic and somnolent between attacks.Infants with intussusception require surgical correction. Prompt laparotomy following diagnosis is crucial for achieving better outcomes. Primary anastomosis can be performed successfully, and stomas can be created in the critically ill patients or those with late detection and septicaemia.

Alpha-fetoprotein (AFP) is a plasma protein produced by the embryonic yolk sac and the fetal liver. AFP levels in serum, amniotic fluid, and urine functions as a screening test for congenital disabilities, chromosomal abnormalities, as well as some other adult occurring tumours and pathologies.Pregnant maternal serum AFP levels are elevated in:- Neural tube defects (e.g., spina bifida, anencephaly)- Omphalocele- Gastroschisis- posterior urethral valves- nephrosis- GI obstruction- teratomas

Supination is the rotation of the forearm so that the palm of the hand faces anteriorly. This is performed by the biceps brachii and supinator of the extensor muscles of the thumb. The opposite action of moving the palm from an anterior-facing position to a posterior-facing position is called pronation. Pronation is performed by the pronator teres and pronator quadratus.

Usage of inhaled corticosteroids are less associated with systemic adverse effects. However they are associated with local complications including dental caries and most commonly dysphonia.

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.

Neuroanatomically, the frontal lobe is the largest lobe of the brain lying in front of the central sulcus. It is divided into 3 major areas defined by their anatomy and function. They are the primary motor cortex, the supplemental and premotor cortex, and the prefrontal cortex. Damage to the primary motor, supplemental motor, and premotor areas lead to weakness and impaired execution of motor tasks of the contralateral side. The inferolateral areas of the dominant hemisphere are the expressive language area (Broca area, Brodmann areas 44 and 45), to which damage will result in a non-fluent expressive type of aphasia.

A lucid interval, in which the patient portrays a temporary improvement in condition after a traumatic brain injury, is especially indicative of an epidural haematoma.

Infantile spasm belongs to the spectrum of seizure disorders. Infantile spasm manifests itself with loss of consciousness and jerky movements. The peak age of onset is between 4 and 6 months. Approximately 90% of infantile spasms begin before 12 months of age. It is rare for infantile spasms to begin during the first 2 weeks of life or after 18 months.

Erythema nodosum (EN) is an acute, nodular, erythematous eruption that usually is limited to the extensor aspects of the lower legs. Chronic or recurrent erythema nodosum is rare but may occur.Currently, the most common cause of erythema nodosum is streptococcal infection in children and streptococcal infection and sarcoidosis in adults.The eruptive phase of erythema nodosum begins with flulike symptoms of fever and generalized aching. Arthralgia may occur and precedes the eruption or appears during the eruptive phase. Most lesions in infection-induced erythema nodosum heal within 7 weeks, but active disease may last up to 18 weeks. In contrast, 30% of idiopathic erythema nodosum cases may last more than 6 months. Febrile illness with dermatologic findings includes abrupt onset of illness with initial fever, followed by a painful rash within 1-2 days.

The next step in the management of this patient is starting a normal saline fluid bolus, following which we should send samples for blood culture, lactate and C-reactive protein. The patient is probably a case of anorexia nervosa (AN).Note:Children with AN are at higher risk of developing infections, and this needs to be considered in this case. Patients with AN may not respond in the usual fashion to sepsis as they may not mount a fever in response to infection. Hypoglycaemia (especially when severe or persistent despite correction) should raise the alarm for an infection as should tachycardia and cool peripheries. Children with severe AN are more likely to be bradycardic. Therefore, a tachycardia should cause the clinician to consider that another process is going on.Other options:- Correcting electrolyte abnormalities is, of course, very important. However, while these are awaited, one needs to consider that this patient is septic and managed accordingly. Children with anorexia nervosa (AN) may have a whole host of electrolyte abnormalities, some of which can be treated with oral or nutritional supplementation although sometimes intravenous correction is required. Electrolytes need to be checked frequently during admission because of the risk of refeeding syndrome, and dietetic input is required to advise on appropriate starting intake.- While maintenance fluids like dextrose are likely to be needed in this case, consideration needs to be given to the underlying cause of the hypoglycaemia. As the sugar has come up following a glucose bolus, a 10% dextrose infusion would be excessive.- An ECG should form a part of any assessment of a child with AN. In this case, it would not be the first thing| however, as part of the acute management of this child, cardiac monitoring should be commenced. One would usually expect a child with AN to be bradycardic so a tachycardia should raise suspicion that another process is going on.- Dietary input will be vital for this child’s ongoing management. However, their acute issues take precedence in this case. Nevertheless, a dietician should be informed and involved from an early stage.

A 3-dimensional transoesophageal echocardiography (3D TEE) provides direct visualization of the entire PFO anatomy and surrounding structures. It allows more accurate diagnosis.

In this case scenario, the pH is too low to be fully explained by a respiratory acidosis. Usually, if there is a metabolic acidosis, the respiratory system will try to compensate by hyperventilation and reduced pCO2. In this case, however, the pCO2 is raised suggesting the presence of a respiratory component.Therefore, this boy has mixed metabolic and respiratory acidosis, most probably due to severe exacerbation of this asthma, which led to diabetic ketoacidosis.Note:Normal values:pH: 7.35 – 7.45pO2: 10 – 14 kPapCO2: 4.5 – 6 kPaBase excess (BE): -2 – 2 mmol/LHCO3: 22 – 26 mmol/L

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

Chickenpox is a highly communicable viral disease caused by human (alpha) herpesvirus 3 (varicella-zoster virus, VZV). It is transmitted from person to person by direct contact (touching the rash), droplet or air born spread (coughing and sneezing).

Absence seizures are induced by over breathing or hyperventilation, while the other features suggest partial seizures.

The most probable cause for the child’s presenting symptoms and the findings in ultrasound would be the presence of an abnormal posterior urethral valve. A posterior urethral valve is a developmental anomaly that usually affects male infants (incidence 1 in 8000) leading to obstructive uropathy. Diagnostic features include bladder wall hypertrophy, hydronephrosis and bladder diverticula.Note:Posterior urethral valves are the most common cause of infra-vesical outflow obstruction in males. They can be diagnosed on antenatal ultrasonography. Due to the necessity of the fetal bladder to develop high emptying pressures in utero secondary to this anomaly, the child may develop renal parenchymal damage. This leads to renal impairment noted in 70% of boys at the time of presentation. Management:The immediate treatment would be to place a bladder catheter to relieve the acutely retained urine. The definitive treatment of choice would be an endoscopic valvotomy with a cystoscopic and renal follow up.

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.

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

Although some individuals with Anorexia Nervosa exhibit no laboratory abnormalities, the semistarvation characteristic of this disorder can affect most major organ systems and produce a variety of disturbances. The induced vomiting and abuse of laxatives, diuretics, and enemas can also cause a number of disturbances leading to abnormal laboratory findings.Haematology: Leukopenia and mild anaemia are common| thrombocytopenia occurs rarely.Chemistry: Dehydration may be reflected by an elevated blood urea nitrogen (BUN). Hypercholesterolemia is common. Liver function tests may be elevated.Hypomagnesemia, hypozincaemia, hypophosphatemia, and hyperamylasaemia are occasionally found. Induced vomiting may lead to metabolic alkalosis (elevated serum bicarbonate), hypochloraemia, and hypokalaemia, and laxative abuse may cause a metabolic acidosis. Serum thyroxine levels are usually in the low-normal range| triiodothyronine levels are decreased. Hyperadrenocorticism and abnormal responsiveness to a variety of neuroendocrine challenges are common.In females, low serum oestrogen levels are present, whereas males have low levels of serum testosterone. There is a regression of the hypothalamic-pituitary-gonadal axis in both sexes in that the 24-hour pattern of secretion of luteinizing hormone (LH) resembles that normally seen in prepubertal or pubertal individuals.

Renal stones < 5mm generally pass spontaneously with adequate fluid intake. Stones 5mm-10mm with pain not resolving, require medical expulsive therapy with Nifedipine or Tamsulosin. For stones larger than 10mm, ESWL or Ureteroscopy is indicated. For stones as big as 2cm, percutaneous nephrolithotomy should be applied.

Perforated appendices are common in children as it is more difficult to surgically assess an unwell child due to poor localisation of abdominal pain, and their inability to express discomfort. They are therefore prone to a greater risk of post operative complications including would infections, intra abdominal fluid collections, and chest infections. In the above scenario the spiking temperature points to an abscess, which characteristically presents with a swinging temperature. The fever is unlikely due to bacterial resistance as blood tests performed post surgery would have indicated any resistance, and a UTI is also unlikely since the child is already on antibiotics. As his chest is clinically clear, a severe chest infection may be ruled out, leaving intra-abdominal collection as the most likely explanation.

Erythema multiforme is a skin rash characterized by the eruption of macules, papules, and target-like lesions. 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, mostly appearing on the distal extremities along with palmoplantar involvement. The disease affects the mucous membrane and orbits as well. The most common infectious cause is herpes simplex virus 1 and 2 to a lesser extent. Inflammation of the adipocytes underlying the skin is referred to as erythema nodosum, and it is not a feature of EM.

The most likely cause of microcephaly in an asymptomatic 3-year-old child is congenital rubella syndrome.Microcephaly is defined as head circumference > two standard deviations below the mean.The causes of microcephaly include:- Genetic disorders: Down syndrome, Edward syndrome, Patau syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome.- Infective: Meningitis, toxoplasmosis, CMV, rubella, varicella, HIVand Zika.- Acquired causes: Severe brain malformations, neurodegenerative diseases, hypoxic-ischemic injury, infarction, antenatal exposure to drugs, alcohol, and other toxins. Severe malnutrition and uncontrolled phenylketonuria in the mother are other causes of microcephaly in children.- Craniosynostosis- Neurometabolic disorders- Early non-accidental trauma- Fanconi anaemia- Other causes include: Familial and nonfamilial nonsyndromic microcephalyMost children with microcephaly have one or several associated symptoms:- Developmental delay- Seizures- Visual abnormalities- Short stature