Deficiency of 21-hydroxylase, resulting from mutations or deletions of CYP21A, is the most common form of Congenital Adrenal Hyperplasia, accounting for more than 90% of cases.Females with mild 21-hydroxylase deficiency are identified later in childhood because of precocious pubic hair, clitoromegaly, or both, often accompanied by accelerated growth and skeletal maturation (simple virilizing adrenal hyperplasia)Diagnosis of 21-hydroxylase deficiency: High serum concentration of 17-hydroxyprogesterone (usually >1000 ng/dL) and urinary pregnanetriol (metabolite of 17-hydroxyprogesterone) in the presence of clinical features suggestive of the disease| 24-hour urinary 17-ketosteroid levels are elevated

Osteoid osteoma is a bone forming tumour which affects individuals in the second decade of life. The patient presents with a history of pain in the lower limbs which is mostly at night and responds to NSAIDS. If the pain doesn’t respond to NSAIDS, then other differentials should be considered.

The thyroid gland is one of the first endocrine glands to develop, and is formed from the endoderm of the epithelial tissue of the primitive pharynx. The mature gland is functionally made up of follicles with colloid which contain the pro hormone thyroglobulin. Thyroid hormone is synthesised at a cellular level and is stored as thyroglobulin, before its release as thyroid hormone, a major modulator of metabolism. In between the follicular cells are parafollicular, or C-cells which secrete parathyroid hormone or calcitonin which are responsible for calcium regulation in the body.

The most common physiological factors that influence renin secretion include renal perfusion pressure, renal sympathetic nerve activity, and tubular sodium chloride load.The perfusion pressure in the renal artery is the most profound parameter to influence renin secretion| when the renal perfusion pressure falls (i.e. hypovolaemia), renin secretion rises, and vice versa.

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.

Bone marrow failure syndromes are characterized by the bone marrow’s inability to produce cells of different lineage. They can be classified as those affecting one or two cell lineages or those affecting all three of them. Fanconi syndrome, along with dyskeratosis congenita, is one of the inherited bone marrow failure syndromes that causes pancytopenia. Other inherited disorders affecting hematopoietic lineage include Diamond-Blackfan anaemia, Schwachman-Diamond syndrome, congenital amegakaryocytic thrombocytopenia (CAMT) and Thrombocytopenia absent radii (TAR) syndrome. Acquired causes of bone marrow failure that lead to pancytopenia include aplastic anaemia, drugs, nutritional deficiencies, and viral infections. Kostmann syndrome is an autosomal recessive form of severe neutropenia, most likely due to excessive neutrophil apoptosis.

A bone age study helps doctors estimate the maturity of a child’s skeletal system. It’s usually done by taking a single X-ray of the left wrist, hand, and fingers. It is a safe and painless procedure that uses a small amount of radiation. The bones on the X-ray image are compared with X-rays images in a standard atlas of bone development, which is based on data from large numbers of other kids of the same gender and age. The bone age is measured in years.

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.

Marfan syndrome is a disorder that affects the connective tissue found throughout the body, Marfan syndrome can affect many systems, often causing abnormalities in the heart, blood vessels, eyes, bones, and joints. The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and aortic root disease, leading to aneurysmal dilatation, aortic regurgitation and dissection is the main cause of morbidity and mortality in Marfan syndrome.

Umbilical vein catheterization utilizes the exposed umbilical stump in a neonate as a site for emergency central venous access up to 14 days old. Umbilical vein catheterization can provide a safe and effective route for intravenous delivery of medications and fluids during resuscitation.The indication for umbilical vein catheterization is when there is a need for IV access in a neonate for resuscitation, transfusions, or short-term venous access when otherwise unobtainable.

The patient’s symptoms are most likely due to phenytoin intake.Note:Hypertrichosis occurs in 5–12% of patients on phenytoin and is most prominent on the extremities. Other options:- Hypertrichosis is the excess hair growth, whereas hirsutism is the development of male-pattern-dependent hair growth, as seen in polycystic ovarian syndrome. – A Becker’s naevus is associated with localised hypertrichosis in the naevus. – Cyclosporine intake can typically lead to diffuse hair growth that begins within 2–4 weeks of starting the drug. – Hereditary gingival fibromatosis is associated with variable hypertrichosis occurring on the eyebrows, face, limbs and mid-back.

The baby may have hydrocephalus and no surgery can be done until it is excluded.Cranial sonography is an important part of neonatal care in general, and high-risk and unstable premature infants, in particular. It allows rapid evaluation of infants in the intensive care units without the need for sedation and with virtually no risk. Expectedly, sonography represents an ideal imaging modality in neonates due to its portability, lower cost, speed, and lack of ionizing radiations. Although there are numerous indications for cranial sonography, it appears to be most useful for detection and follow-up of intracranial haemorrhage, hydrocephalus, and periventricular leukomalacia (PVL).

Key observations in the results:

1. Oxygen Saturation Step-Up:
   • There is a significant step-up in oxygen saturation from the right ventricle (72%) to the pulmonary artery (86%). This suggests the presence of left-to-right shunting of blood.
2. Pressure Differences:
   • The pressure in the pulmonary artery is elevated (53/13 mmHg), indicating pulmonary hypertension.

Differential Diagnosis:

1. Patent Ductus Arteriosus (PDA):
   • PDA can cause increased pulmonary blood flow, leading to a step-up in oxygen saturation in the pulmonary artery. The pulmonary artery pressures can also be elevated due to increased blood flow.
2. Primary Pulmonary Hypertension:
   • Typically presents with elevated pulmonary pressures but does not usually show a step-up in oxygen saturation.
3. Pulmonary Stenosis:
   • Would result in elevated right ventricular pressure but would not explain the step-up in oxygen saturation.
4. Septum Primum Atrial Septal Defect (ASD):
   • Would result in a step-up in oxygen saturation from the right atrium to the right ventricle, not between the right ventricle and pulmonary artery.
5. Tetralogy of Fallot:
   • Characterized by right ventricular outflow tract obstruction, VSD, right ventricular hypertrophy, and an overriding aorta. Oxygen saturation levels would typically be lower in the systemic circulation.

The gastrocolic reflex is a physiological reflex that involves increase in colonic motility in response to stretch in the stomach and by-products of digestion in the small intestine. It is shown to be uneven in its distribution throughout the colon, with the sigmoid colon affected more than the right side of the colon in terms of a phasic response. Various neuropeptides have been proposed as mediators of this reflex, such as serotonin, neurotensin, cholecystokinin and gastrin.

The most probable diagnosis in this patient would be pulmonary stenosis. Pulmonary Stenosis:Pulmonary valve murmurs are heard in the upper left sternal edge, associated with a thrill but no desaturation in the absence of an additional shunt. The ECG changes suggest right ventricular hypertrophy. Pulmonary stenosis is often well tolerated in childhood unless severe. These should be monitored with serial echocardiography, and balloon pulmonary valvoplasty should be considered once the pressure gradient reaches 64 mmHg.Other options:- Atrial septal defect: While atrial septal defects are associated with right ventricular outflow tract murmurs, they would not cause a thrill.- Patent ductus arteriosus: PDA murmurs can be audible in the left upper sternal edge, but would normally be audible in the left infraclavicular area and be continuous rather than ejection systolic. This left to right shunt would not cause desaturation but does cause left-sided volume loading and hence left-sided ECG changes.- Tetralogy of Fallot: Ventricular septal defect, overriding aorta, subpulmonary stenosis, and right ventricular hypertrophy. This would often cause a ULSE murmur with a thrill and RVH on ECG. However, this degree of obstruction would cause shunting from right to left, and this child would be desaturated.- Ventricular septal defect: Isolated ventricular septal defects cause pansystolic murmurs at the left lower sternal edge. They would have left-sided ECG changes and normal saturations (in the absence of pulmonary hypertension).

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.

Anorexia nervosa is associated with a decrease in muscle mass, which is one of the primary locations of creatinine metabolism. Due to this, plasma creatinine levels are found to be decreased in patients with anorexia. Other blood chemistry derangements in patients of anorexia nervosa include hypercortisolism, hypoglycaemia, low free T3 levels, and hypercholesterolemia.

Benign neonatal sleep myoclonus (BNSM) is a disorder commonly mistaken for seizures during the new-born period. It is characterized by myoclonic lightninglike jerks of the extremities that exclusively occur during sleep| it is not correlated with epilepsy.Causes of neonatal seizures:Hypoxic-ischemic encephalopathy: Hypoxic-ischemic encephalopathy disrupts the ATP-dependent sodium-potassium pump and appears to cause excessive depolarization.Intracranial haemorrhage: occurs more frequently in premature than in term infants. Subarachnoid haemorrhage is more common in term infants. This type of haemorrhage occurs frequently and is not clinically significant. Typically, infants with subarachnoid haemorrhage appear remarkably well. Metabolic disturbances include hypoglycaemia, hypocalcaemia, and hypomagnesemia. Less frequent metabolic disorders, such as inborn errors of metabolism, are seen more commonly in infants who are older than 72 hours. Typically, they may be seen after the infant starts feeding.Intracranial infections (which should be ruled out vigorously) that are important causes of neonatal seizures include meningitis, encephalitis (including herpes encephalitis), toxoplasmosis, and cytomegalovirus (CMV) infections. The common bacterial pathogens include Escherichia coli and Streptococcus pneumoniae.Cerebral malformationsBenign neonatal seizures

Hirsutism is the growth of excess hair in androgen dependent areas or in a male pattern. The phenomenon is found in conditions where there is abnormal androgen action. This can occur in adrenal lesions including congenital adrenal hyperplasia, and Cushing syndrome, or a failure to produce adequate female hormones such as PCOS and premature menopause. Similarly, drugs such as anabolic steroids, danazol and minoxidil can also cause hirsutism. Delayed puberty is unlikely to cause hirsutism.

An odds ratio (OR) is a measure of the association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions). Wherea = Number of exposed casesb = Number of exposed non-casesc = Number of unexposed casesd = Number of unexposed non-casesOR=(a/c) / (b/d) = ad/bc

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.

The thymus is a lymphoid organ located in the anterior mediastinum. In early life, the thymus is responsible for the development and maturation of cell-mediated immunologic functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T cells.DiGeorge’s syndrome (DGS) is a developmental abnormality affecting the thymus. The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcaemia (resulting from parathyroid hypoplasia).

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

Metformin works by improving the sensitivity of peripheral tissues to insulin, which results in a reduction of circulating insulin levels. Metformin inhibits hepatic gluconeogenesis and it also increases the glucose uptake by peripheral tissues and reduces fatty acid oxidation. Metformin has a positive effect on the endothelium and adipose tissue independent of its action on insulin and glucose levels.Metformin was the first insulin sensitising drug (ISD) to be used in PCOS to investigate the role of insulin resistance in the pathogenesis of the syndrome Several effects have been reported as related to metformin in PCOS patients including restoring ovulation, reducing weight, reducing circulating androgen levels, reducing the risk of miscarriage and reducing the risk of gestational diabetes mellitus (GDM). Other studies have reported that the addition of metformin to the ovarian stimulation regime in invitro fertilization (IVF) improves the pregnancy outcome. These effects will be addressed individually.

After a period of 14 days, if jaundice persists in a term new-born, having ruled out the other possibilities, biliary atresia should be considered as a possible diagnosis.Biliary atresia is a rare but serious condition. Symptoms include obstructive jaundice (dark urine and pale stool). Management:Surgery within 8 weeks is recommended. Survival is around 90% using current treatment regimes. Without treatment, children will survive to around 18 months.

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.

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

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.

The baby is not clearing CO2 normally despite normal oxygenation so we should increase the delta P. Higher delta P will increase tidal volume and hence CO2 removal.After initial resuscitation and stabilization, the following should be the ventilator settings used:Rate: 30-40/minutePeak inspiratory pressure (PIP) – determined by adequate chest wall movement.An infant weighing less than 1500 grams: 16-28 cm H2O.An infant weighing greater than 1500 grams: 20-30 cm H2O. Positive end expiratory pressure (PEEP): 4 cm of H2O OR 5-6 cm if FiO2 > 0.90.FiO2: 0.4 to 1.0, depending on the clinical situation.Inspiratory time: 0.3-0.5 sec.After 15 to 30 minutes, check arterial blood gases and pH.If the PaO2 or the O2 saturation is below accepted standards, the FiO2 can be raised to a maximum of 1.0. If the PaO2 or O2 saturation is still inadequate, the mean airway pressure can be raised by increasing either the PIP, PEEP, inspiratory time or the rate, leaving inspiratory time constant.If the PaCO2 is elevated, the rate or peak inspiratory pressure can be raised.