Xq27.1 Duplication Encompassing SOX3: Variable Phenotype and Smallest Duplication Associated with Hypopituitarism to Date - A Large Case Series of Unrelated Patients and a Literature Review.

BACKGROUND: Xq27.1 duplication encompassing SOX3 has been implicated in the aetiology of X-linked hypopituitarism associated with intellectual disability and neural tube defects. We describe the largest case series to date of 5 unrelated patients with SOX3 duplication with a variable clinical phenotype, including the smallest reported SOX3 duplication. CASE REPORTS: Five male patients who presented with congenital hypopituitarism (CH) were identified to have Xq27.1 duplication encompassing SOX3. The size of the duplication ranged from 323.8 kb to 11 Mb. The duplication was maternally inherited or de novo in 2 patients each (and of unknown inheritance in 1 patient). The age at presentation was variable. Three patients had multiple pituitary hormone deficiencies, whereas 2 patients had isolated growth hormone deficiency. All patients had micropenis and/or small undescended testes. Structural pituitary and/or other midline cranial abnormalities (callosal hypogenesis/absence of the septum pellucidum) were present in all patients. Two patients had a neural tube defect in addition to CH. CONCLUSIONS: This is the largest series reported to date of unrelated patients with CH in association with Xq27.1 duplication encompassing SOX3. The clinical phenotype is variable, which may be due to genetic redundancy or other unknown aetiological factors. We have expanded the phenotypic spectrum through description of the smallest Xq27.1 duplication (323.8 kb) with CH reported to date, as well as a second family with CH and a neural tube defect.

A 16-year-old boy with emphysematous gastritis and oesophageal candidiasis.

Emphysematous gastritis is a rare and frequently fatal condition caused by invasion of gas-forming bacteria into the gastric wall. There have only been a handful of reported cases in the paediatric population, and none of these have evidence of candidal infection or mucormycosis. Patients typically present with abdominal pain, vomiting, malaena and haematemesis. Risk factors for emphysematous gastritis are those that interfere with the natural barriers to infection in the stomach. Diagnosis is made on the basis of typical appearances on abdominal CT. Treatment is generally conservative with surgery reserved for failed medical management or later complications. Antimicrobial cover should be broad with a low threshold for antifungals. It is important to look for predisposing factors for this condition, perhaps including an assessment of the patient's immunocompetency. We present a 16-year-old boy with global developmental delay who presented with this condition associated with candidal infection.