Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-Mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

Vagus nerve lesions will affect the gag reflex since the pharyngeal muscles are innervated by it.
The vagal nerve (10th cranial nerve ) is a mixed nerve carrying motor efferents and sensory afferents. The nerve conducts five distinct qualities, which are carried along general visceral efferent fibres (parasympathetic innervation of pharyngeal, laryngeal, bronchial, and gastrointestinal mucosa), general visceral afferent fibres (sensory information from the thoracic and abdominal viscera, the aortic body, aortic arch), special visceral afferent fibres (carry the taste of the epiglottal region), general somatic afferent fibres (carry sensation from the external auditory meatus, outer tympanic membrane, back of the ear, part of meninges, pharynx), and along special visceral efferent fibres, which innervate skeletal muscles of the pharynx and larynx.

Skeletal muscles innervated by the vagal nerve include the cricothyroid, levator veli palatini, salpingopharyngeus, palatoglossal, palatopharyngeus pharyngeal constrictor, and the laryngeal muscles (except cricothyroid). Innervation of these muscles is involved during speech or opening of the larynx during breathing.

Efferent parasympathetic fibres control heart rate, peristalsis, and sweating. Stimulation of the efferent parasympathetic fibres lowers heart rate or blood pressure. 80-90% of the vagal fibres are afferent, only 10-20% are efferent fibres

Physical exam of the 10th cranial nerve includes eliciting the gag reflex (The gag reflex involves a brisk and brief elevation of the soft palate and bilateral contraction of pharyngeal muscles evoked by touching the posterior pharyngeal wall.), to look if the uvula is deviated from the side of the lesion, if there is failure of palate elevation upon phonation, and evaluation of speech impairment.
In case of bilateral vagal nerve lesions, heart rate and breath rate may be increased. The somatic sensory function can be assessed by testing the sensibility of the external auditory meatus.

Adrenaline (epinephrine) narrows blood vessels and opens airways in the lungs. These effects can reverse severe low blood pressure, wheezing, severe skin itching, hives, and other symptoms of an allergic reaction.

The most probable diagnosis in this patient would be hyphaema.

The acuity has varied because the blood has been settling in the anterior chamber of the eye, thus allowing a reasonable level of visual acuity.
The size of the tennis ball (which is not as harmful as a squash ball in the eye) and the fact that it was struck from a distance would cause a moderately significant injury due to pressure to the globe.

Other options:
– The absence of severe pain makes a large corneal abrasion less likely.
– Vitreous haemorrhage would lead to very poor acuity, more likely ‘hand movements only’.
– A retinal detachment or traumatic cataract would not produce such immediate symptoms, and if they did occur it would probably be in the presence of more extensive eye trauma and pain, with additional signs of both hyphaema and vitreous haemorrhage.

The most probable diagnosis for this patient would be Coarctation of Aorta (CoA).

Infants with CoA present within the first few weeks of life with signs suggestive of congestive cardiac failure and general circulatory shock. In these patients, the aorta is supplied by the right ventricle, via the ductus arteriosus.

Pathophysiology:
When the left ventricle supplies the aorta via the aortic isthmus, children are usually asymptomatic or may present with occasional complaints of leg pain.
Associated cardiac anomalies are uncommon but for a bicuspid aortic valve, which is present in approximately 50% of cases.
Good collateral circulation usually develops in these patients, which in the long term, causes notching of ribs.

Clinical Presentation:
Clinically, there may be hypertension in the upper limbs (or higher BP readings than in the lower limbs), and leg pulses are absent, or weak and delayed. A systolic click and aortic ejection systolic murmur are heard, caused by the bicuspid aortic valve.

Management:
The primary medical management is to treat hypertension. After stabilization, the patient can undergo definitive surgical repair.

Transcatheter balloon angioplasty of the coarctation is controversial, but ballooning +/- stenting of re-coarctation following surgery is commonly performed.
Systemic hypertension may occur following repair, even in the absence of re-coarctation necessitating the re-initiation/continuation of antihypertensive therapy in these patients.

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.

Henoch-Schonlein purpura (HSP), also known as IgA vasculitis, is a disease of the skin, mucous membranes, and sometimes other organs that most commonly affects children. In the skin, the disease causes palpable purpura (small, raised areas of bleeding underneath the skin), often with joint pain and abdominal pain. It is an acute immunoglobulin A (IgA)-mediated disorder. The tetrad of purpura, arthritis, kidney inflammation, and abdominal pain is often observed.

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

Reed-Sternberg cells are classically associated with Hodgkin lymphoma.
Classical diagnostic Reed-Sternberg cells are large (15 to 45 micrometres), have abundant slightly basophilic or amphophilic cytoplasm and have at least two nuclear lobes or nuclei. Diagnostic Reed-Sternberg cells must have at least two nucleoli in two separate nuclear lobes. The nuclei are large and often rounded in contour with a prominent, often irregular nuclear membrane, pale chromatin and usually one prominent eosinophilic nucleolus, with perinuclear clearing (halo), resembling a viral inclusion.

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.

Carbon monoxide is a colourless gas, which is toxic to animals. It has a high affinity for haemoglobin (around 250 times greater than oxygen). It combines with haemoglobin forming carboxyhaemoglobin, which decreases the oxygen-carrying capacity of the blood, leading to a left-shift in the oxygen-dissociation curve. CO is produced endogenously in limited amounts (0.4ml per hour), but the toxic levels are higher.

The presentation of the patient and the characteristic ring-like (Bull’s eye) rash are highly suggestive of a diagnosis of Lyme disease caused by Borrelia burgdorferi. The spirochete is transmitted by Ixodid ticks.

The initial presentation of this infection includes an erythema migrans rash that starts from the site of tick bite and gradually expands. Other features supporting the diagnosis are the history of camping, fever, joint pain, and the neurological symptoms presenting as facial nerve palsy.

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.

This is the clinical picture of dermatitis herpetiformis associated with gluten-sensitive enteropathy. To establish the diagnosis, you should measure the coeliac antibodies.
Darrier’s sign (where the skin urticates when it is stroked) is positive in urticaria pigmentosa.

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. 

PARACHUTE REFLEX
This reflex occurs in slightly older infants when the child is held upright and the baby’s body is rotated quickly to face forward (as in falling). The baby will extend his arms forward as if to break a fall, even though this reflex appears long before the baby walks.
Newborn reflexes are:
Rooting reflex:
This reflex starts when the corner of the baby’s mouth is stroked or touched. The baby will turn his or her head and open his or her mouth to follow and root in the direction of the stroking. This helps the baby find the breast or bottle to start feeding. This reflex lasts about 4 months.
Suck reflex:
Moro reflex:
The Moro reflex is often called a startle reflex. That’s because it usually occurs when a baby is startled by a loud sound or movement. In response to the sound, the baby throws back his or her head, extends out his or her arms and legs, cries, then pulls the arms and legs back in. This reflex lasts until the baby is about 2 months old.
Tonic neck reflex:
When a baby’s head is turned to one side, the arm on that side stretches out and the opposite arm bends up at the elbow. This is often called the fencing position. This reflex lasts until the baby is about 5 to 7 months old.
Grasp reflex:
Stroking the palm of a baby’s hand causes the baby to close his or her fingers in a grasp. The grasp reflex lasts until the baby is about 5 to 6 months old. A similar reflex in the toes lasts until 9 to 12 months.
Stepping reflex:
This reflex is also called the walking or dance reflex because a baby appears to take steps or dance when held upright with his or her feet touching a solid surface. This reflex lasts about 2 months.

Cystic fibrosis has an autosomal recessive pattern of inheritance, meaning that a person might be a carrier of the disease without developing it. If the unaffected partner is a carrier, then there is a 50% chance of inheritance and a 50% chance of having a child who is a carrier. However, if the partner is not a carrier, the offspring will not develop the disease but the possibility of being a carrier raises up to 100%.

Age (years) Respiratory rate (per minute) Heart rate (per minute) Systolic blood pressure
<1 30-40 110-160 70-90
1-2 25-35 100-150 80-95
2-5 25-30 95-140 80-100
5-12 20-25 80-120 90-110
>12 15-20 60-100 100-120

Adapted from Advanced Paediatric Life Support Manual

Haemophilia A and haemophilia B are inherited in an X-linked recessive pattern. The genes associated with these conditions are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition.

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.

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

Nissl body is a neuron-specific cellular structure. It is composed of rough endoplasmic reticulum and fine granules. The rough endoplasmic reticulum contains free ribosomes, and are the hub of protein synthesis. When these substances are exposed to a cresyl violet solution, they show selective-staining by turning purple-blue. In pathologic processes, they may undergo chromatolysis.

Bitemporal hemianopia is a characteristic finding seen in patients with optic chiasm lesion.

The pituitary gland is situated within the pituitary fossa. Just above the pituitary fossa is the optic chiasm and so any expanding masses from the pituitary gland commonly press on it, causing bitemporal hemianopia.

Other options:
– Compression of the optic nerve would not cause more severe, generalised visual loss. Also, the optic nerve is not anatomically related to the pituitary gland and so is unlikely to be directly compressed in the presence of a pituitary tumour.
– The optic tract is again not closely anatomically related with the pituitary gland and so is unlikely to be directly compressed in the presence of a pituitary tumour. Also, damage to the optic tract on one side would cause homonymous hemianopia.
– The lateral geniculate nucleus is a centre of cells in the thalamus and is unlikely to be compressed by a pituitary tumour. Its function is to convey sensory information from the optic tract to more central parts of the visual pathway.
– The Edinger-Westphal nucleus is located at the level of the superior colliculus in the midbrain and so may not be compressed by an enlarging pituitary tumour.

Other visual defects:
– Left homonymous hemianopia: It is the visual field defect to the left, due to the lesion of the right optic tract.
– Homonymous quadrantanopias are seen in parietal (inferior homonymous quadrantopia) and temporal lobe lesions (superior homonymous quadrantopia). Mnemonic: PITS (Parietal-Inferior, Temporal-Superior)

A congruous defect means complete or symmetrical visual field loss, and conversely, an incongruous defect is incomplete or asymmetric.
Incongruous defects suggest an optic tract lesion, while congruous defects suggest optic radiation or occipital cortex lesion.

Tanner stage two presents with the following: Downy hair, Breast bud palpable under areola (1st pubertal sign in females).

Stage 1 (prepubertal) – elevation of papilla only – no pubic hair
Stage 2 – breast bud forms – sparse, slightly pigmented hair on labia majora
Stage 3 – Breast begins to become elevated, extends beyond areola borders – hair becomes more coarse and curly
Stage 4 – increased size and elevation. Areola and papilla form secondary mound – adult like, but sparing medial thighs
Stage 5 – final size, areola returns but papilla remains projected – hair extends to medial thighs

The central nervous system comprises of two types of cells; neurons and neuroglial cells. Glial cells are the support cells that serve a number of important functions. Three types of neuroglia comprise the mature nervous system, which are ependymal cells, microglia, and macroglia. The macroglia are of two types oligodendrocytes and astrocytes. Microglia are the neuroglial cells that serve the function of phagocytosis since they are derived from the hematopoietic stem cells and share properties with tissue macrophages. They remove the cellular debris from the site of injury or normal cellular turnover by performing scavenger function.

EPICure is a series of studies of survival and later health among babies and young people who were born at extremely low gestations -from 22 to 26 weeks.

Boost II is a double-blind randomised controlled trial (RCT) comparing the effects of targeting arterial oxygen saturations between 85% and 89% versus 91% and 95% in preterm infants.

OSCAR Xe is not the name of a study. Baby-OSCAR is an RCT to determine whether a confirmed large patent ductus arteriosus in very premature babies should be treated with ibuprofen within 72 hours of birth.

SafeBoosC is a trial to examine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants in the first 72 hours of life with the use of NIRS oximetry and a clinical treatment guideline.

TOBY Xe is an RCT looking at the neuroprotective effects of hypothermia combined with inhaled xenon following perinatal asphyxia.

History of recurrent infections and failure to thrive (probably due to pancreatic enzyme insufficiency) is highly suggestive of cystic fibrosis. Pseudomonas has been identified as an important respiratory pathogen in patients with cystic fibrosis.

The most appropriate imaging modalities to be used in this child would be CT Head, C-spine and Abdomen/Pelvis and chest X-ray (CXR).

The C-spine cannot be cleared, this alongside a multi-trauma presentation means a CT C-spine is indicated rather than X-rays alone. The imaging modality for blunt trauma to the chest is CXR; if this shows significant thoracic trauma, a CT chest should be considered.

Other options:
– CT Head and Abdomen/Pelvis with CXR and X-ray C-spine: This child is at risk of C-Spine injury following the mechanism of trauma. He had a reduced GCS, has undergone a multi-region trauma and is now intubated. NICE head injury guidelines, therefore, recommend using CT.
– CT Head, C-spine and Abdomen/Pelvis X-rays: Imaging of the chest is required following blunt trauma and for endotracheal tube position.
– MRI Head: If there were concerns of abnormal neurology, then spinal MRI could be considered.
– Whole-body CT: It is not recommended in children in view of the high radiation doses.

Scaphoid fractures are regarded as fractures that are difficult to heal, so a classification system is needed taking different factors into account that should lead towards proper guidance to the healing time and management of these fractures. Popular classification criteria are Herbert, Russe, and Mayo classification systems. Herbert’s classification system is based on the fracture’s stability and proposes that all complete bicortical fractures (except for tubercle fractures) are unstable. Salter-Harris classification is used for categorizing epiphyseal fractures, while Delbert classification system is reserved for fractures of the proximal femur in children. Fractures of the ankles are classified using Ottawa rules, and Garland classification is used for supracondylar fractures in children.

Among the given options, pituitary adenoma is an acquired anterior pituitary disorder which represent between 10 and 25% of all intracranial neoplasms.

Other options:
– Agenesis of the corpus callosum is characterised by the partial or complete absence of the corpus callosum. This condition is associated with pituitary hormone deficiencies.
– Congenital disorders such as hydrocephalus or arachnoid cysts may be a cause of precocious puberty.
– Pituitary hypoplasia and septo-optic dysplasia are congenital disorders of the pituitary gland.

DiGeorge syndrome is one of the most common microdeletion syndromes, resulting from 22q11 deletion. 10% of the cases can be inherited in an autosomal dominant fashion, while 90% are sporadic. The syndrome is characterized by a deficiency of both T and B-cell lines along with hearing loss, 20-fold increased lifetime chances of developing schizophrenia, renal abnormalities, congenital heart defects, and a borderline or low IQ. Distinctive facial features include micrognathia, long face, short philtrum, cleft palate, and small teeth.

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.

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

Haemolytic disease of the new-born due to ABO incompatibility is usually less severe than Rh incompatibility. One reason is that fetal RBCs express less of the ABO blood group antigens compared with adult levels. In addition, in contrast to the Rh antigens, the ABO blood group antigens are expressed by a variety of fetal (and adult) tissues, reducing the chances of anti-A and anti-B binding their target antigens on the fetal RBCs.

ABO HDN occurs almost exclusively in the offspring of women of blood group O, although reports exist of occasional cases in group A mothers with high-titre anti-(group B) IgG

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

Certain lesions present on x-ray are suggestive of child abuse including rib, humerus and skull fractures. It is the doctors responsibility to follow up on these cases to determine whether domestic abuse has occurred.

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

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.

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

The red reflex examination is an important part of the paediatric ocular assessment. The red reflex is abnormal in conditions like retinoblastoma, retinopathy of prematurity, cataract, and retinal detachment.
Amblyopia is a cortical developmental disorder that results in defective visual inputs to both the eyes. The disorder occurs during the cortical plasticity stage of embryonic development. The red reflex is normal in this case since there is no hindrance to the reflection of light from the ocular media and fundus.

The clinical scenario presented is highly suggestive of vitamin C deficiency (Scurvy).

Vitamin C is found in citrus fruits, tomatoes, potatoes, Brussel sprouts, cauliflower, broccoli, cabbage and spinach.
Deficiency leads to impaired collagen synthesis and disordered connective tissue.
Scurvy is associated with severe malnutrition as well as drug and alcohol abuse, and those living in poverty with limited access to fruits and vegetables.

Symptoms and signs include:
– Follicular hyperkeratosis and perifollicular haemorrhage
– Ecchymosis
– Gingivitis with bleeding and receding gums
– Sjogren’s syndrome
– Arthralgia
– Oedema
– Impaired wound healing
– Generalised symptoms such as weakness, malaise, anorexia and depression

Puberty is the general term for the transition from sexual immaturity to sexual maturity. There are two main physiological events in puberty:
– Gonadarche is the activation of the gonads by the pituitary hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
– Adrenarche is the increase in production of androgens by the adrenal cortex. It is the term for the maturational increase in adrenal androgen production that normally becomes biochemically apparent at approximately six years of age in both girls and boys

A number of other terms describe specific components of puberty:
– Thelarche is the appearance of breast tissue, which is primarily due to the action of oestradiol from the ovaries.
– Menarche is the time of first menstrual bleed.
– Pubarche is the appearance of pubic hair, which is primarily due to the effects of androgens from the adrenal gland. The term is also applied to first appearance of axillary hair, apocrine body odour, and acne.

The earliest detectable secondary sexual characteristic on physical examination in most girls is breast/areolar development (thelarche). Ovarian enlargement and growth acceleration typically precede breast development but are not apparent on a single physical examination. Oestrogen stimulation of the vaginal mucosa causes a physiologic leukorrhea, which is a thin, white, non-foul-smelling vaginal discharge that typically begins 6 to 12 months before menarche. Menarche occurs, on average, 2 to 2.5 years after the onset of puberty

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 dysenteriae
E Coli
Salmonella typhi
Campylobacter jejuni
Yersinia pseudotuberculosis
Neisseria meningitidis
S pneumonia
Legionella pneumophila
Mycoplasma species
Rickettsial infections may include Rocky Mountain spotted fever and microtatobiotes

Viral infections may include the following:
Human immunodeficiency virus (HIV)
Coxsackievirus
Echovirus
Influenza virus
Epstein-Barr virus
Herpes simplex virus
Fungal infections can include Aspergillus fumigatus.

Vaccinations may include the following:
Influenza triple-antigen vaccine
Typhoid-paratyphoid A and B (TAB) vaccine
Polio vaccine

Pregnancy-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.

Haemophilia is a X-linked recessive disorder. In X-linked recessive inheritance only males are affected. An exception to this seen in examinations are patients with Turner’s syndrome, who are affected due to only having one X chromosome. X-linked recessive disorders are transmitted by heterozygote females (carriers) and male-to-male transmission is not seen. Affected males can only have unaffected sons and carrier daughters.

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. The laboratory results will usually include fragmented RBCs, decreased serum haptoglobin, reduced platelet count, nonspecific WBC changes, and normal coagulation tests (PTT included).

NICE guidelines suggest that at the premonitory stage (pre-hospital) the patient should receive Diazepam 10−20 mg given rectally, or midazolam 10 mg given buccally. If seizures continue, the patient should receive lorazepam IV.

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

Based on the clinical scenario, the most probable diagnosis in this patient is Kallmann’s syndrome.
Kallmann’s syndrome is due to isolated gonadotrophin-releasing hormone (GnRH) deficiency. It is often inherited in an X-linked recessive manner.

Other options:
– While Klinefelter’s syndrome is also associated with hypogonadism, the other clinical features of Klinefelter’s are not seen.
– Cryptorchidism is ruled out by the presence of testes in the scrotum.
– The presentation of the child is not suggestive of mumps orchitis or hyperprolactinaemia.

Normal QT interval in a 6 months old baby is < 0.44 seconds. A duration exceeding this value is referred to as QT interval prolongation, which is associated with some important congenital syndromes that include Brugada syndrome which is characterized by vasovagal syncope and sudden cardiac death, Jervell and Lange-Nielsen syndrome which is associated with congenital deafness, Andersen syndrome which is marked by bone deformities, and Timothy syndrome with associated heart disease and immunodeficiency.
Romano-Ward syndrome is the commonest cause of congenital QT prolongation with no associated extra-cardiac manifestations.
Lown-Ganong-Levine syndrome is characterized by a shortened PR interval and a normal QRS duration.

Progressive vomiting due to pyloric stenosis leads to hypochloraemic, hypokalaemic, metabolic alkalosis.

Infants exposed to maternal HIV and with positive results require immediate management with co-trimoxazole prophylaxis, regardless of their CD4 levels. Antiretroviral treatment is necessary as well but it could wait until further work-up is complete.

Auscultatory findings of VSD vary with the size of the defect. Small VSDs typically produce murmurs ranging from a grade 1 to 2/6 high-pitched, short systolic murmur (due to tiny defects that actually close during late systole) to a grade 3 to 4/6 holosystolic murmur (with or without thrill) at the lower left sternal border; this murmur is usually audible within the first few days of life (see table Heart Murmur Intensity). The precordium is not hyperactive, and the 2nd heart sound (S2) is normally split and has normal intensity.

Moderate to large VSDs produce a holosystolic murmur that is present by age 2 to 3 wk; S2 is usually narrowly split with an accentuated pulmonary component. An apical diastolic rumble (due to increased flow through the mitral valve) and findings of heart failure (e.g., tachypnoea, dyspnoea with feeding, failure to thrive, gallop, crackles, hepatomegaly) may be present. In moderate, high-flow VSDs, the murmur is often very loud and accompanied by a thrill (grade 4 or 5 murmur). With large defects allowing equalization of left ventricular and right ventricular pressures, the systolic murmur is often attenuated.

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.

Among the given options, lipoatrophy takes time to develop as it is a long-term complication of insulin therapy. Since it has only been two weeks since the initiation of insulin therapy, it is unlikely to occur so early.
The risk of lipoatrophy is reduced with newer insulins and also can be avoided by site rotation.
However, anaphylaxis, allergic reactions, infection and abscesses at the site of an insulin pump can occur in this patient as a complication of insulin therapy.

External oblique forms the outermost muscle of the three muscles comprising the anterolateral aspect of the abdominal wall. Its aponeurosis comprises the anterior wall of the inguinal canal.

Normal cerebrospinal fluid (CSF) glucose together with lymphocytosis, an increased opening pressure and raised CSF protein are typical of a viral meningitis.

Ewing’s sarcoma is formed by small, round, blue cells, and is common in children. The usually develop in limbs, and clinical findings include pain and inflammation, with lytic destruction showing up on X-rays.

Cranial nerve VI, also known as the abducent nerve, innervates the ipsilateral lateral rectus (LR), which functions to abduct the ipsilateral eye.
Patients usually present with an isolated abduction deficit, binocular horizontal diplopia, worse in the distance, and esotropia in primary gaze. Patients also may present with a head-turn to maintain binocularity and binocular fusion and to minimize diplopia
Examination for a sixth nerve palsy involves documenting the presence or absence of papilledema, examining the ocular motility, evaluating the eyelids and pupils, and excluding involvement of other cranial nerves (e.g., V, VII, VIII).

The differentiation between type 1 and type 2 epithelia in the developing lung buds is evident from 16-24 weeks of gestation.

Development of the respiratory tract has five stages:

– Embryonic (at 4 – 5 weeks of gestation):
Formation of lung buds, trachea and mainstem bronchi occur. These structures are formed from a ventral outpouching of foregut pharynx. At this stage, the beginnings of the five lung lobes are present.
– Pseudoglandular (at 5 – 16 weeks of gestation):
Formation of terminal bronchioles, cartilage and smooth muscles occur in this stage.
– Canalicular (at 16-24 weeks gestation):
Differentiation of type I and II epithelial cells can be done in this stage. There is also an increase in the size of proximal airways).
– Saccular (at 24 – 40 weeks of gestation): Terminal saccule formation occurs. Production of surfactant takes place at this stage with an increase in the number of goblet cells
Up to half the adult number of alveoli are in place by this stage.
– Alveolar (occurs between 32 weeks of gestation till the post-natal age 8): Formation of alveoli and septation occurs with the expansion of air spaces.

Cystinosis is a condition characterized by accumulation of the amino acid cystine (a building block of proteins) within cells.
This condition is inherited in an autosomal recessive pattern.
Excess cystine damages cells and often forms crystals that can build up and cause problems in many organs and tissues. The kidneys and eyes are especially vulnerable to damage; the muscles, thyroid, pancreas, and testes may also be affected.
There are three distinct types of cystinosis. In order of decreasing severity, they are nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis.
Nephropathic cystinosis begins in infancy, causing poor growth and a particular type of kidney damage (renal Fanconi syndrome) in which certain molecules that should be reabsorbed into the bloodstream are instead eliminated in the urine. The kidney problems lead to the loss of important minerals, salts, fluids, and many other nutrients. The loss of nutrients impairs growth and may result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. The nutrient imbalances in the body lead to increased urination, thirst, dehydration, and abnormally acidic blood (acidosis). By about the age of 2, cystine crystals may be present in the clear covering of the eye (cornea). The build-up of these crystals in the eye causes pain and an increased sensitivity to light (photophobia). Untreated children will experience complete kidney failure by about the age of 10. Other signs and symptoms that may occur in untreated people, especially after adolescence, include muscle deterioration, blindness, inability to swallow, diabetes, thyroid and nervous system problems, and an inability to father children (infertility) in affected men.
The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age.

Eczema is an immune-mediated inflammatory condition of the skin characterized by intense pruritis and scaly rashes over the body. The impact of the disease can be measured by using certain scales, which include the Dermatitis Family Impact (DFI) Questionnaire, infant’s Dermatitis Quality of Life Index, Patient-oriented Eczema Measure, and Children’s Dermatology Life Quality Index among many others. Eczema severity questionnaire is not a recognized scale to determine eczema impact.

The drainage of cerebral spinal fluid from the third ventricle to the fourth ventricle is carried out by the cerebral aqueduct. The cerebral aqueduct is the narrowest passageway in the entire ventricular system and thus forms the most common site of blockage of flow of cerebrospinal fluid. The interventricular foramen allows passage of CSF to the third ventricle. The foramen of Luschka and Magendie are located on the fourth ventricle and allow passage of CSF to the subarachnoid space from the ventricular system. The pontine cistern is a space located on the ventral aspect of the pons. The cisterna magna is an opening on the subarachnoid space between the pia matter and the arachnoid.

Ventilatory rates of 40-60 breaths/min should be provided initially, with proportionally fewer assisted breaths provided if the infant’s spontaneous respiratory efforts increase. Although this practice has not been extensively studied, initial inflation of the new-born’s lungs with either slow-rise or square-wave inflation to a pressure of 30-40 cm H2 O for approximately 5 seconds has been reported to result in more rapid formation of Functional Residual Capacity (FRC).
At the moment of delivery and first breath, the neonatal lung is converting from a fetal non-aerated status to a neonatal status. The neonatal lung requires gas exchange, and this necessitates the development of FRC with the resorption of lung fluid and the resolution of most of the atelectasis. Therefore, initial slow ventilation with more prolonged inspiratory times may be useful to assist in this task, balanced against the need to avoid inappropriate inspiratory pressures.
Flow-controlled, pressure-limited mechanical devices are acceptable for delivering PPV. These mechanical devices control flow and limit pressure and be more consistent than bags. Self-inflating and flow-inflating bags remain a standard of care. Laryngeal mask airways are effective for assisted ventilation when bag-mask ventilation and intubation are unsuccessful.

Achondroplasia is one of the commonest forms of skeletal dysplasias that lead to dwarfism. Multiple skeletal deformities are associated with it but the common cranial abnormalities are macrocephaly, frontal bossing, depressed nasal bridge, narrowed foramen magnum, and the presence of communicating hydrocephalus. A prominent maxilla is not associated with achondroplasia.

According to the Rumack-Matthew Normogram, accurate levels of paracetamol can be measured only between 4-15 hours. The levels measured before 4 hours post-ingestion would highly underestimate the level of paracetamol ingested.
The patient in question presents 2 hours after ingestion. Hence the most appropriate time to measure the levels of acetaminophen would be a further 2 hours later.

Other options:
– Note that the treatment with NAC can be delayed until the 4-hour level is obtained and compared to the nomogram.
– Furthermore, haemodialysis is only indicated if she develops hepato-renal syndrome that is likely to occur 72-96 hours post-ingestion.
– Indications for acute liver transplantation include persistent acidosis, hepatorenal syndrome and worsening coagulopathy.

Coarctation of the aorta is one of the serious forms of congenital heart diseases Occurring in about 1 in 2,500 births. It is characterized by a congenitally narrowed proximal thoracic aorta. Coarctation can occur in isolation but can accompany other cardiac lesions, including a bicuspid aortic valve in 70% of the cases and berry aneurysms in 10% of the cases. Coarctation of the aorta is commonly found in association with Turner’s syndrome, Edward’s syndrome, and Patau syndrome.

HUS syndrome occurs mostly in children after some days of bloody diarrhoea. Damaged red blood cells also damage the kidney filtering unit and lead to sudden renal failure.

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

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic academia. The condition gets its name from the distinctive sweet odour of affected infants’ urine, particularly prior to diagnosis, and during times of acute illness. MSUD, also known as branched-chain ketoaciduria, is an aminoacidopathy due to an enzyme defect in the catabolic pathway of the branched-chain amino acids leucine, isoleucine, and valine.

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

A lumbosacral lipoma is a form of congenital spinal lipoma and can be regarded as a cutaneous marker of dysraphism. It is not a skin condition but rather represents a defect in the process of neurulation and leads to a constellation of other abnormalities. The most common other systemic abnormalities associated with midline lumbosacral lipoma include complex anorectal and urological malformations. Other mentioned conditions are benign rashes or birthmarks.

The level of statistical significance is often expressed as a p-value between 0 and 1. The smaller the p-value, the stronger the evidence that you should reject the null hypothesis.

A p-value less than 0.05 (typically ≤ 0.05) is statistically significant. It indicates strong evidence against the null hypothesis, as there is less than a 5% probability the null is correct (and the results are random). Therefore, we reject the null hypothesis, and accept the alternative hypothesis.
However, this does not mean that there is a 95% probability that the research hypothesis is true. The p-value is conditional upon the null hypothesis being true is unrelated to the truth or falsity of the research hypothesis.
A lower p-value is sometimes interpreted as meaning there is a stronger relationship between two variables. However, statistical significance means that it is unlikely that the null hypothesis is true (less than 5%).

To understand the strength of the difference between two groups (control vs. experimental) a researcher needs to calculate the effect size.

Based on the clinical scenario, the most likely risk factor in this child to develop gallstones is sickle cell disease.

Note:
Haemolysis is the most frequent cause for gallstones in children and the likeliest cause because of his ethnicity would be sickle cell disease. The gallstones are pigmented which form from bilirubin. 70% of patients with sickle cell disease will develop gallstones; the prevalence of gallstones is related to the rate of haemolysis.

Other options:
– Gilbert’s syndrome: it is a common condition in which bilirubin glucuronidation (i.e. converting bilirubin into a water-soluble form) is affected. During times of stress (viral illness, fasting, etc.) there is an excess bilirubin production, and jaundice may develop. It is a benign condition but there is some evidence of an increased risk of developing gallstones. However, sickle cell disease is a more likely risk factor in this case.
– Hereditary spherocytosis: Hereditary spherocytosis is a disease of the white population and is less likely to be the underlying cause in this case.
– Male gender: After puberty, the incidence of gallstones is higher in women. Before puberty, the incidence is equal.
– Obesity: Obesity is a risk factor for gallstones and is thought to be behind the rising incidence among young adults. Nevertheless, haemolytic states remain the most common reason for gallstones in children.

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).

Precocious puberty refers to the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal.
Most patients, particularly girls suspected of having central precocious puberty, are otherwise healthy children whose pubertal maturation begins at the early end of the normal distribution curve
In a series of more than 200 patients evaluated at a single medical centre, central precocious puberty occurred 5 times more often in girls than boys.
GnRH-dependent precocious puberty is treated with GnRH agonists or Luteinizing Hormone Releasing Hormone (LHRH).
Follow up every 4-6 months to ensure that progression of puberty has been arrested
Favourable signs include normalization of accelerated growth, reduction (or at least no increase) in size of breasts, and suppression of gonadotropin levels after a challenge of GnRH
The ideal testing frequency has not been established. Monitor bone age yearly to confirm that the rapid advancement seen in the untreated state has slowed, typically to a half year of bone age per year or less

The best answer is Henoch-Schonlein Purpura (HSP). This patient has a characteristic rash and the labs are consistent with this diagnosis.

Capillary haemangiomas (strawberry naevi) are very common benign tumours that may appear in infancy. This particular case requires a close follow-up to monitor the naevus’ size and make sure it doesn’t expand or gets bigger, affecting the baby’s visual field.

It is more common in preterm babies and girls are 3x more commonly affected than boys. It presents at birth in 30%, and is a focal and solitary in 80% of cases, most commonly found on the head and neck (60%), followed by the trunk (25%) and extremities (15%).

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.

Based on the patient’s presentation, he’s probably suffering from
Leiner’s disease

Leiner’s disease is a severe generalised form of seborrhoeic dermatitis. It is also associated with recurrent diarrhoea, recurrent skin and internal infections, and failure to thrive.

Seborrhoeic dermatitis is a common and self-limiting condition in childhood. Lesions affect the scalp (cradle cap), and sometimes the ear, nose, and eyebrows. It is characterised by greasy yellow or yellow-brown scales.

There is an association with Malassezia, and the lesions are a reaction to this yeast, rather than caused by it.

It is most common in the 6-12 month age group. Simple brushing with a soft bristle brush, use of oil or emollient, and ketoconazole 2% shampoo are all treatment options.

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.

The child is suffering from acute sickle cell crisis, a complication of sickle cell disease. It is characterised by a new segmental pulmonary infiltrate consistent with consolidation together with one or more new respiratory symptoms.
The mainstay of treatment is oxygen support, (ventilation if required), hydration, antibiotics and analgesia.

Relative risk = (Incidence in exposed group)/incidence in unexposed group). So in this case RR = (50/100)/(50/200) = 2.

Identify babies as being more likely to develop significant hyperbilirubinemia if they have any of the following factors:
– gestational age under 38 weeks
– a previous sibling with neonatal jaundice requiring phototherapy
– mother’s intention to breastfeed exclusively
– visible jaundice in the first 24 hours of life.

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.

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.

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.

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 disability
Learning problems
Attention deficit-hyperactivity disorder
Initial focal seizures progressing to frequent, secondarily generalized seizures
Increasing seizure frequency and duration despite the use of antiepileptic drugs (AEDs)
Increasing duration of a transient postictal deficit
Increase in focal or diffuse atrophy – Determined by serial neuroimaging
Progressive increase in calcifications
Development of hemiparesis
Deterioration in cognitive functioning

Physical signs of SWS are as follows:
Port-wine stain
Macrocephaly
Ocular manifestations
Soft-tissue hypertrophy
Hemiparesis
Visual loss
Hemianopsia

Ocular involvement in SWS may include the following signs:
Buphthalmos
Glaucoma
Tomato-catsup colour of the fundus (ipsilateral to the nevus flammeus) with glaucoma
Conjunctival and episcleral haemangiomas
Diffuse choroidal haemangiomas
Heterochromia of the irides
Tortuous retinal vessels with occasional arteriovenous communications

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

Adhesion formation might be reduced by minimally invasive surgical techniques and the use of adhesion barriers. Non-operative treatment is effective in most patients with ASBO. Contraindications for non-operative treatment include peritonitis, strangulation, and ischemia. When the adhesive aetiology of obstruction is unsure, or when contraindications for non-operative management might be present, CT is the diagnostic technique of choice. The principles of non-operative treatment are nil per os, naso-gastric, or long-tube decompression, and intravenous supplementation with fluids and electrolytes. When operative treatment is required, a laparoscopic approach may be beneficial for selected cases of simple ASBO.

The most probable diagnosis for this boy is primary hypothyroidism.

Rationale:
The development of secondary sexual characteristics in a boy aged less than 9 years of age is highly suggestive of precocious puberty.

Around 80% of boys with precocious puberty have pathological causes and require detailed investigation.
In this case, the child has long-standing short stature but coupled with the early puberty and delay in bone age, the diagnosis is primary hypothyroidism, which is the only cause of this clinical picture.

HLA-DR (3 and 4) have been associated with an increased risk for idiopathic diabetes mellitus.
Type 1 diabetes has a high heritability compared to type 2
Identical twins have a 30-50% risk if their twin has type 1 diabetes

Time- Event
Week 1: Implantation
Week 2: Formation of bilaminar disk
Week 3: Formation of primitive streak
Formation of notochord
Gastrulation
Week 4: Limb buds begin to form
Neural tube closes
Heart begins to beat
Week 10: Genitals are differentiated

Port-wine stains are a type of vascular birthmark caused by the abnormal development of capillaries in the skin. These pinkish-purplish discolorations present at birth and are associated with medical conditions such as Sturge-Weber syndrome, a neurocutaneous disorder involving the leptomeninges. Port wine stains are therefore associated with epilepsy, glaucoma or intellectual disability common in Sturge-Weber syndrome. Additional complications of Port wine stains include a loss of function if near the eye or mouth due to hypertrophy, or glaucoma if near the eyelid.

Diabetes ketoacidosis is one of the most serious and acute complications of diabetes. At the time of presentation and during treatment of diabetic ketoacidosis (DKA), several metabolic and electrolyte derangements can ultimately result in respiratory compromise. Most commonly, hypokalaemia, hypomagnesemia and hypophosphatemia can eventually lead to respiratory muscles failure. Furthermore, tachypnoea, hyperpnea and more severely, Kussmaul breathing pattern can develop. Also, hydrostatic and non-hydrostatic pulmonary oedema can occur secondary to volume shifts into the extracellular space and secondary to increased permeability of the pulmonary capillaries. The presence of respiratory failure in patients with DKA is associated with higher morbidity and mortality. Being familiar with the causes of respiratory compromise in DKA, and how to treat them, may represent better outcomes for patients with DKA.

The history is suggestive of a post-traumatic seizure which frequently occurs after moderate or severe traumatic brain injury. Although upgoing plantars can be identified in a post-ictal status, an intracranial bleed has to be excluded. A single seizure cannot be considered epilepsy

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