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.

Celiac disease is classified as a Type IV hypersensitivity mediated by T-cell response. Negatively charged gliadin has been shown to induce interleukin 15 in the enteric epithelial cells, stimulating the proliferation of the natural killer cells and intraepithelial lymphocytes to express NK-G2D, a marker for natural killer T lymphocytes.

Based on the clinical scenario, the boy is going through normal pubertal changes.In the 3 years before puberty, low pulsatile LH levels become detectable during sleep. LH and FSH are produced in the anterior pituitary and released due to pulsatile gonadotrophin-releasing hormone (GnRH) secreted by the hypothalamus. There is an increase in the amplitude and frequency of LH secretion as puberty approaches, which causes enlargement of the gonads. In boys, the testicles produce testosterone, and in girls, the ovaries produce oestradiol and ovarian androgens, which, with the adrenal androgens, produce secondary sexual characteristics.Note:The average age at onset of puberty is 11 years in girls. The first sign is breast bud development, followed by the appearance of pubic hair 6–12 months later. Menarche usually occurs 2–2.5 years after breast bud development. Peak height velocity in girls occurs at breast stage 2–3 and virtually always precedes menarche. The onset of puberty in boys is at 11.5 years. The first sign is testicular enlargement (>3 ml) and thinning of the scrotum. This is followed by the pigmentation of the scrotum and growth of the penis, and pubic hair follows. Peak height velocity (growth spurt) is two years later in boys than in girls and occurs at testicular stage 4–5 (i.e. testicular volume 10–12 ml), which is around 13–14 years of age. Breast enlargement occurs in 40–60% of boys (rarely, significant enough to cause social embarrassment in 10%) and is a result of oestradiol produced by the metabolism of testosterone. It usually resolves within three years. During puberty, elongation of the eye often occurs, causing short-sightedness.

Histology of psoriasis is characterised by parakeratosis (cell nuclei within stratum corneum) and thickened projections of the prickle cell layer of keratinocytes (psoriasiform hyperplasia or acanthosis). Orthokeratosis refers to the formation of a pathological anuclear keratin layer in the skin.The stratum granulosum is actually thinned or absent in patients with psoriasis.

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.

Case control studies are observational studies which retrospectively determine whether a patient might have been exposed to a risk factor for a certain disease, as compared to a control group from the general population. They can be used for a range of outcomes as well as rare diseases. One of the biggest problems with this type of study is recall bias. Research subjects may selectively remember factors that are more predictive of the disease outcome when compared to the control group. All studies should have prior power calculations before the study commences.

ABC : Airway, breathing, circulation is the order of assessment in any patient that is unconscious and apnoeic.

Ectoderm derivatives include the adrenal medulla, posterior pituitary, the epidermis of the skin, nails, hair, sweat glands, mammary glands, sebaceous glands, the central nervous system, the peripheral nervous system, the retina and lens of eye, the pupillary muscle of the iris, melanocytes, Schwann cells and odontoblasts.

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

According to the Gell and Coombs classification of hypersensitivity reactions, the scenario provided is a type 4 (delayed) reaction.These reactions are mediated by T lymphocytes and cause contact dermatitis. Nickel, commonly found in cheap jewellery, is a common cause of contact dermatitis.Note:There are two main types of contact dermatitis:- Irritant contact dermatitis: It is a common, non-allergic reaction due to weak acids or alkalis (e.g. detergents). These are often seen on the hands. They present typically with erythema, and rarely, crusting and vesicles.- Allergic contact dermatitis: These are type IV hypersensitivity reactions and are often seen on the head following hair dyes.They typically present as acute weeping eczema which predominately affects the margins of the hairline rather than the hairy scalp itself. Treatment is usually with a potent topical steroid.Other options:- Allergic rhinitis is an example of a type 1 (immediate) reaction. It is an IgE mediated. It is a hypersensitivity to a previously innocuous substance.- Type 2 reactions are mediated by IgG and IgM, which binds to a cell, causing cell death. Goodpasture syndrome is an example of a type 2 hypersensitivity reaction.- Immune complexes mediate type 3 reactions. Rheumatoid arthritis is an example of a type 3 hypersensitivity reaction.

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.

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.

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.

The most important test recommended among the given options is the measurement of creatine kinase levels.The child presents with a gross motor developmental delay, and multiple investigations can be undertaken to confirm the diagnosis. However, the clinching point in the given clinical scenario is the presence of a positive Gower’s sign.Gower’s sign is an excellent screening test for muscle weakness, which is typically observed as an early clinical feature of Duchenne muscular dystrophy (DMD).Creatinine kinase measurement is an easy and rapid test to aid in the diagnosis. Early diagnosis has significant implications not only for the child but for the family, particularly for genetic counselling. DMD is an X-linked recessive disorder, with an abnormal gene at the X chromosome at the Xp21 locus. It is a progressive degenerative muscular condition where muscle fibres are replaced by fat and fibrosis (i.e., become dystrophic).

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.

The selection process is based on five requirements and essentially aims to select a random representative cohort through:1.Isolating a group for which there is a greater or lesser chance of detecting a possible difference between the treatments compared|2.Establishing a homogeneous group in order to reduce the variability of response, thus making statistical comparison more sensitive and decreasing the risk of bias due to the constitution of non-homogeneous groups|3.Obtaining representative samples of the affection studied|4.Defining the rules corresponding to realistic recruitment|5.Respecting ethical obligations.

Spontaneous intestinal perforation (SIP) of the new-born, also referred to as isolated perforation or focal intestinal perforation (FIP) of the new-born, is a single intestinal perforation that is typically found at the terminal ileum. SIP occurs primarily in preterm infants with very low birth weight (VLBW, birth weight <1500 g) and extremely low birth weight (ELBW, birth weight <1000 g), umbilical catheter placement, maternal drug use and twin-to-twin transfusion syndrome. SIP is a separate clinical entity from necrotizing enterocolitis, the most severe gastrointestinal complication of preterm infants.

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

The Meckel’s diverticulum is a vestigial remnant of the omphalomesenteric duct. This structure is also referred to as the vitelline and contains two types of ectopic tissue, namely| gastric and pancreatic.

Hyposplenism is associated with thrombocytosis. Other features of hyposplenism are: – Howell-Jolly bodies and acanthocytosis, occurring secondary to haemolysis.- Pappenheimer bodies: These are granular deposits of iron found within the RBCs.- Lymphocytosis and monocytosis.Causes for hyposplenism include:- Congenital asplenia- Iatrogenic splenectomy: Following trauma or treatment for ITP, thalassemia or spherocytosis).- Autosplenectomy: Secondary to sickle cell anaemia, coeliac disease, dermatitis herpetiformis, essential thrombocythemia or splenic arterial thrombosis).

The main aim of randomisation in a clinical trial is to remove the bias and avoid any potential confounding variables. While in double blind studies both the investigators and the patients are not aware of which group they belong in, being blind is not essential in carrying out a randomized study, nor is it essential that the randomisation be done away from the study centre. A placebo also does not facilitate randomisation, which can be done in single centre and multi-centre trials.

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

The combination of cholestasis, congenital heart disease (mainly affecting the pulmonary vasculature) and anterior-segment abnormalities (primarily posterior embryotoxon) suggests a diagnosis of Alagille syndrome. Clinical features:The facial features are characteristic and include a prominent forehead, deep-set eyes and a pointed chin. The most common skeletal manifestation is butterfly vertebrae, a clefting abnormality of the vertebrae most often seen in the thoracic spine and described in up to 87% of cases. Radio-ulnar synostosis and short phalanges have also been described in Alagille but less frequently. Note: Pectus excavatum is a feature of Noonan syndrome, one of the differential diagnoses of pulmonary valve disease.

The patient’s sugar levels typically show the Dawn phenomenon.Dawn phenomenon:This is an early morning rise in blood glucose levels secondary to a rise in hormones that increase blood glucose levels. The question suggests that he is undergoing a pubertal growth spurt, suggesting that an increase in these hormones is what has led to the higher morning glucose levels.Other options:- Inactivity at night-time: It is expected, and insulin dose should be adequate despite inactivity during the night.- Inadequate bedtime insulin: It is possible that this is a contributing factor. However, inadequate background insulin is also likely to result in high blood glucose in the day, which the question does not suggest.- Somogyi effect: There are no features suggestive of nocturnal hypoglycaemia that can cause the Somogyi effect.- Nocturnal glycogenesis: Glycogenesis would result in hypoglycaemia, not hyperglycaemia.

The most probable cause for the patient’s presenting symptoms is Sarcoptes scabeii.Scabies:The boy in the scenario presents with a pruritic rash affecting the palms of the hands, especially in the web spaces between the fingers. Additionally, the fact that his sister is showing similar symptoms is an indication of its infectivity. The female Sarcoptes scabiei var hominis mite burrows into the webs of fingers and the sides of digits as seen in the child.This parasitic skin infestation presents typically with nocturnal itching. Other options:- Herpes simplex virus type 1 (HSV-1): This can affect this age group but would usually present with a vesicular perioral rash with associated erythema. – Human papillomavirus (HPV): Cutaneous human papillomavirus infection causes warts, which can form a dome and fleshy shaped lesions on the palms of the hands, but these are not usually itchy. Similar to the causative agent in the boy, they are contagious.- Poxvirus: These viruses cause molluscum contagiosum which presents as dome-shaped lesions anywhere on the body, rather than specifically in palms of hands or finger webs as seen in the boy. Poxviruses are also very infectious.- Staphylococcal infection: This causes impetigo, which presents with yellow discharge and underlying erythema. Impetigo is not usually itchy and can present on any part of the body, rather than the specific areas seen in the boy.

Buckwheat is not wheat. It’s a seed rather than a grain, which means it’s gluten-free and safe for people with celiac disease and non-celiac gluten sensitivity. It is an excellent source of fibre and nutrients.

Relative risk is the probability of an outcome occurring in an exposed group as compared to the probability of that outcome in an unexposed group. In the scenario given, 50% of the children exposed developed the disease while only 10% of the children who were unexposed developed the disease. The relative risk was therefore 50/10=5. There is no further information about whether the study was controlled, the confidence interval, or the type of study. It therefore cannot be confirmed whether the chemical is causative and if it should be avoided.

Hydrocephalus is a serious medical condition resulting from excessive accumulation of cerebrospinal fluid in the brain leading to abnormal pressure build-up inside the brain. Hydrocephalus can be categorized into two types according to the flow of CSF between the ventricles. When the CSF flows freely between the ventricles, but is blocked after it exits the ventricular system, the hydrocephalus is said to be a communicating hydrocephalus. When the flow of CSF within the ventricles is blocked, the resulting hydrocephalus is termed as obstructive, or non-communicating. The communicating hydrocephalus is caused by insufficient reabsorption of CSF in the subarachnoid space, which is also observed in cases of bacterial meningitis, in which inflammatory process leads to the thickening of the leptomeninges and thereby reduces CSF reabsorption. Arnold Chiari malformation is associated with obstructive hydrocephalus due to blocked ventricles. Congenital aqueduct stenosis causes the blockage of third and lateral ventricles. Congenital atresia of the foramen of Monro leads to blocked lateral ventricles and thus results in obstructive hydrocephalus. Tumour of the posterior fossa is associated with blockage of the fourth ventricle outflow.

Answer: Acute Epstein Barr virus infectionThe Epstein–Barr virus is one of eight known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. Infection with Epstein-Barr virus (EBV) is common and usually occurs in childhood or early adulthood.EBV is the cause of infectious mononucleosis, an illness associated with symptoms and signs like:fever,fatigue,swollen tonsils,headache, andsweats,sore throat,swollen lymph nodes in the neck, andsometimes an enlarged spleen.Although EBV can cause mononucleosis, not everyone infected with the virus will get mononucleosis. White blood cells called B cells are the primary targets of EBV infection.Petechiae on the palate are characteristic of streptococcal pharyngitis but also can be seen in Epstein–Barr virus infection, Arcanobacterium haemolyticum pharyngitis, rubella, roseola, viral haemorrhagic fevers, thrombocytopenia, and palatal trauma.

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).