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.

Fine motor development involves greater use of the hands to perform more precise tasks. By 6 -12 months children should be able to reach for small objects and pass an object from one hand to the other. From 1 -2 years they can perform more complex tasks such a building a tower of blocks, feeding themselves, and turning knobs. In terms of pencil skills, they should be able to imitate scribbles and then spontaneously scribble. By the age of 2 years they can draw a line, and by three they can draw a circle. From the age of 3.5 they can draw a cross, 4.5 – a square, 5 – a triangle, and 6 a diamond.

McBurney’s point is found 2/3rds of the way along an imaginary line that runs from the umbilicus to the anterior superior iliac spine on the right-hand side.
On examination, features of generalised peritonitis can be observed if the appendix has perforated.
Retrocecal appendicitis may have relatively fewer signs.
Digital rectal examination may reveal boggy sensation if a pelvic abscess is present.
Diagnosis is typically based on raised inflammatory markers coupled with compatible history, and examination findings.
Ultrasound is useful in females where pelvic organ pathology can be a close differential diagnosis.
Although it is not always possible to visualise the appendix on ultrasound, the presence of free fluid (always pathological in males) should raise suspicion. Ultrasound examination can also show evidence of luminal obstruction and thickening of the appendix.

Management:
Definitive management of appendicitis and appendicular perforation is appendicectomy which can be performed via either an open or laparoscopic approach.
Simultaneous administration of metronidazole reduces wound infection rates. Patients with perforated appendicitis require copious abdominal lavage.
Patients without peritonitis who have an appendix mass should receive broad-spectrum antibiotics and consideration given to performing an interval appendicectomy.

Meconium ileus equivalent (MIE) can be defined as a clinical manifestation in cystic fibrosis (CF) patients caused by acute intestinal obstruction by putty-like faecal material in the cecum or terminal ileum. A broader definition includes a more chronic condition in CF patients with abdominal pain and a coecal mass which may eventually pass spontaneously. The condition occurs only in CF patients with exocrine pancreatic insufficiency (EPI). It has not been seen in other CF patients nor in non-CF patients with EPI. The frequency of these symptoms has been reported as 2.4%-25%.

The treatment should primarily be non-operative. Specific treatment with N-acetylcysteine, administrated orally and/or as an enema is recommended. Enemas with the water soluble contrast medium, meglucamine diatrizoate (Gastrografin), provide an alternative form for treatment and can also serve diagnostic purposes. It is important that the physician is familiar with this disease entity and the appropriate treatment with the above mentioned drugs. Non-operative treatment is often effective, and dangerous complications following surgery can thus be avoided.

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

Frequent regurgitation of milk and microcytic anaemia is suggestive of a hiatus hernia. The reflux causes regurgitation of milk and frequent ulceration of the lower oesophageal mucosa potentially resulting in blood loss and anaemia. Duodenal atresia usually presents with bilious vomiting and pyloric stenosis presents with projectile vomiting. Alpha 1 antitrypsin deficiency and cystic fibrosis usually do not present with vomiting.

Non Epileptic attack disorder, also known as psychogenic non epileptic seizures, is a condition characterised by episodes of abnormal movement and behaviours that resemble seizures , but are not caused by electrical activity changes in the brain. It is believed that the disorder is caused by the brain’s response to overwhelming or stressful situations. In Jamila’s case, triggering conditions for her episodes may have been the absence of her mother, and the stress of her upcoming examinations. A diagnosis of generalised epilepsy is unlikely because this would require abnormal movement in all 4 limbs during an episode and a longer period of semi consciousness after. Cataplexy can also be ruled out as it does not involve a loss of consciousness which we see in Jamila’s case. Vasovagal syncope does not correspond with the history as there was no evidence of simultaneous collapse and responsiveness coupled with colour change and near spontaneous recovery when supine. A complex partial seizure may be possible in Jamila’s case, however the history of long duration, her eyes being tightly shut and the differences in presentation between the two episodes makes it less likely.

Children are very prone to dehydration during an episode of gastroenteritis. Dehydration is detected early by increased capillary filling time.

Case control studies are used to determine the relationship between exposure to a risk factor and the resultant outcomes. It finds patients in the general population who have a certain condition and retrospectively searches for past exposure to possible risk factors for the disease. Controls are people who do not have the disease found in the general population. This type of study is useful for rare diseases, and is less time consuming to conduct.

While cohort studies can be used to study rare diseases they measure the relative risk of developing the disease over time based on exposure.

Ecological or cross-sectional studies attempt take a snapshot of a whole population, and thus are inappropriate for rare diseases as larger sample numbers are needed. A randomised control trial is better suited to determine the effect of an intervention.

Among the given options, psoriasis is not associated with hypertrichosis.

The causes of hypertrichosis include:
– Drugs: minoxidil, ciclosporin, and diazoxide.
– Congenital hypertrichosis lanuginosa and congenital hypertrichosis terminalis.
– Porphyria cutanea tarda
– Anorexia nervosa

Infective endocarditis (IE) is an acute infective pathology of the endocardium secondary to some underlying cardiac pathology like VSD and TOF. Most commonly, it is bacterial in origin, caused by staphylococcus aureus in the majority of cases. Clinical features include fever, arthralgias, weight loss, anorexia, new-onset, or changing existing murmur. Skin manifestations include Osler’s nodes, Janeway lesions, splinter haemorrhages, and clubbing. Roth spots are conjunctival haemorrhages found in IE. Beau’s lines are not found in IE.

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

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.

While the results of this before and after study can provide some preliminary insight into the effects of the dietary intervention, the results should be viewed with great caution as they may be considered merely anecdotal. The lack of a control group contributes to confounding the data. Therefore, while the difference may be statistically significant and the confidence interval is compatible with a fall in the number of seizures after therapy, the results cannot be introduced as the standard without a control group to compare with.

The second pharyngeal arch or hyoid arch, is the second of six pharyngeal arches that develops in fetal life during the fourth week of development and assists in forming the side and front of the neck. Derivatives:

Skeletal – From the cartilage of the second arch arises:

Stapes,

Temporal styloid process,

Stylohyoid ligament, and

Lesser cornu of the hyoid bone.

Muscles:

Muscles of face

Occipitofrontalis muscle

Platysma

Stylohyoid muscle

Posterior belly of Digastric

Stapedius muscle

Auricular muscles

Nerve supply: Facial nerve

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

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

The most appropriate step in this patient would be to admit the patient for enteral rehydration via a nasogastric tube.

Enteral rehydration:
Oral rehydration is the most preferred way of rehydrating children. If a child is not tolerating small-frequent-feeds, then nasogastric rehydration is an underused next best step.
The fluid can be run through a continuous pump so that it is better tolerated.

Note:
Intravenous fluids are effective but can have profound effects on the serum electrolyte balance if not monitored closely.
Most children will tolerate fluids in an emergency department, but failure to take fluids orally is not an indication for intravenous therapy.

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.

Based on the findings presented, the sign elicited is Rovsing’s sign.

Rovsing’s sign:
It is a sign suggestive of appendicitis. A positive sign is determined when palpation in the left lower quadrant of a patient’s abdomen causes pain in the right lower quadrant.

Other options:
– Murphy’s sign is positive in gallbladder inflammation. With the upper border of the examiner’s hand in the right upper quadrant of the abdomen under the rib cage, the patient is asked to inhale. Inhalation causes the gallbladder to descend, which catches on the fingers, causing pain.
– Cullen’s sign is suggestive of ectopic pregnancy or acute pancreatitis and describes the bruising around the umbilicus.
– Tinel’s sign is positive in those with carpal tunnel syndrome. The examiner’s fingers tap the median nerve over the flexor retinaculum, which causes paraesthesia over the distribution of the median nerve.
– Battles’ sign describes bruising behind the ear, suggesting a basal skull fracture of the posterior cranial fossa.

Clinical diagnosis of neurofibromatosis type 1 requires the presence of at least 2 of 7 criteria to confirm the presence of neurofibromatosis, type 1. Many of these signs do not appear until later childhood or adolescence, and thus confirming the diagnosis often is delayed despite a suspicion of NF1.
The 7 clinical criteria used to diagnose NF1 are as follows:
– Six or more cafe-au-lait spots or hyperpigmented macules greater than 5 mm in diameter in prepubertal children and greater than 15 mm postpubertal
– Axillary or inguinal freckles (>2)
– Two or more typical neurofibromas or one plexiform neurofibroma
– Optic nerve glioma
– Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist
– Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis
– A first-degree relative (e.g., mother, father, sister, brother) with NF1

The most prudent course of action in the given clinical scenario is an ovary-sparing cystectomy. The history is 3-months and is already chronic. Furthermore, the cyst is greater than 5cm in size and at risk of torsion. This will relieve the cause of pain, reduce the risk of torsion and save ovarian function.

Other options:
– This is a simple cyst and not a malignancy, so imaging and referral are not indicated.
– Open oophorectomy was done in the past. However, this is very aggressive, and the modern approach is ovary-sparing.
– As the cyst is 7cm and at risk of torsion, conservative management is not appropriate.

Mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity may present in adolescence or adulthood with oligomenorrhea, hirsutism, and/or infertility. This is termed nonclassical adrenal hyperplasia.
Late-onset or nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Reported prevalence ranges from 1 in 30 to 1 in 1000. Affected individuals typically present due to signs and symptoms of androgen excess.
Treatment needs to be directed toward the symptoms. Goals of treatment include normal linear growth velocity, a normal rate of skeletal maturation, ‘on-time’ puberty, regular menstrual cycles, prevention of or limited progression of hirsutism and acne, and fertility. Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.
Normal Ultrasound rules out Turner’s syndrome.

Idiopathic hypercalciuria (IH) is the commonest metabolic abnormality in patients with calcium kidney stones. It is characterized by normocalcemia, absence of diseases that cause increased urine calcium, and calcium excretion that is above 250 mg/day in women and 300 mg/day in men. Subjects with IH have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, negative calcium balance is commonly seen in balance studies, especially on a low calcium diet. The mediator of decreased renal calcium reabsorption is not clear; it is not associated with either an increase in filtered load of calcium or altered PTH levels. There is an increased incidence of hypercalciuria in first-degree relatives of those with IH, but IH appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion. Increased tissue vitamin D response may be responsible for the manifestations of IH in at least some patients.

Unprotected anal or vaginal sexual intercourse with an infected individual is by far the most common (95%) route by which HIV is transmitted.

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

Based on the presenting features, the patient has developed a septal haematoma after the trauma.

Septal hematoma:
In this condition, blood collects between the septal cartilage and the perichondrium.
The patient classically presents with symptoms of nasal difficulty and pain following a nasal injury.
Care should be taken not to misdiagnose a septal haematoma as a blood clot on the septum. In the case of a septal haematoma the swelling will typically be visible on both sides of the septum although this is not always the case.
Referral to an ENT surgeon is indicated because, if untreated, there is a high risk of cartilage breakdown and complications related to infection.

Other options:
– The nosebleed has now stopped therefore compression is no longer required. The boy has developed a septal haematoma after traumatic injury.
– CT head is not indicated in this patient as the diagnosis is clearly a septal hematoma.
– Management of a septal hematoma consists of drainage and antibiotics. There is no role for intranasal corticosteroids.
– If untreated, there is a high risk of cartilage breakdown and complications related to infection. Thus, referral to the ENT is essential; reassurance and discharge can lead to complications.

PDA is particularly common in premature babies and it is managed by indomethacin administration. However, if PDA is not the only defect, prostaglandin E1 can be administered in order to keep the ductus open until the surgery takes place.

Klinefelter syndrome is a chromosomal disease that does not lead to congenital cataracts. A congenital cataract is the clouding of the cornea that is present from birth. Causes can be categorized as genetic, infectious, and metabolic. The most common infectious cause is congenital rubella syndrome. Galactosemia is a metabolic cause of congenital cataracts. Down’s syndrome represents a genetic cause of congenital cataract.

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

The most probable diagnosis for the above clinical scenario, of a child presenting with motor and vocal tics for more than a year is highly suggestive of a diagnosis of Tourette syndrome.

The symptoms often wax and wane, and although several different drugs are available, none are entirely useful, and side-effects are relatively common.

With these considerations in mind, it is essential to try and avoid treatment initially as the tics can spontaneously improve with time.

Informing the teacher and class about the nature of the condition and allowing the child ‘time out’ to tic might help to avoid the need for medication.