Endocrine Abstracts (2017) 51 P043 | DOI: 10.1530/endoabs.51.P043

SOX3 gene duplication (OMIM 313430) associated with midline CNS malformations, hypopituitarism and neurodevelopmental abnormalities: 3 unrelated cases

Aparna K.R. Nambisan1, Ritika Kapoor1, Michal Ajzensztejn2, Tony Hulse2 & Charles R. Buchanan1


1Kings College Hospital, London, UK; 2Evelina Children’s Hospital, London, UK.


Introduction: Duplications of the SOX3 gene at Xq27.1 are known to be associated with a spectrum of forebrain midline defects, isolated or multiple pituitary hormone deficiencies, spina bifida and sometimes learning difficulties. We report three cases of SOX3 duplication with hypopituitarism and differing presentations.

Case reports: 1) A male infant presented in neonatal period with poor feeding, prolonged jaundice, central hypothyroidism and inadequate cortisol response to Synacthen. Hormone replacement with hydrocortisone, thyroxine and subsequently growth hormone was commenced. MRI showed pituitary hypoplasia and ectopic poster pituitary with normal septum pellucidum and corpus callosum. Karyotype in infancy was normal. Array CGH (aged 2 years) revealed duplication of the SOX3 gene (maternal ly derived). He has a maternal adult male cousin with hypopituitarism. By age 4 years he had severe expressive language delay which improved with therapy. Aged 9.9 years he is of normal stature. 2) A 15-year old boy was referred with short stature and pubertal delay. He had brachycephaly, learning difficulties, dyspraxia and hyposmia. Initial endocrine assessment was consistent with constitutional delay and he received a course of testosterone treatment. He subsequently failed to progress spontaneously in puberty (G3, PH3, TVs 5–6 ml aged 16 years). IGF-1 was low, peak GH 6.1 mcg/l (post glucagon) with normal cortisol. MRI showed partial agenesis of corpus callosum and absent septum pellucidum. Array CGH showed maternally derived duplication of SOX3. Aged 20 years he is on full testosterone replacement. 3)A male infant was noted on antenatal scan to have lumbar meningomyelocoele (repaired with VP shunt). Post-natal imaging showed hydrocephalus and agenesis of corpus callosum. He had micropenis, small testes; normal thyroid function and cortisol response to Synacthen in week 1 of life. Array CGH revealed de novo duplication of SOX3 and part of chromosome6. Age 2years peak GH 4.4 ug/l and cortisol 452 nmol/l (post-glucagon), IGF1 4.8 nmol/l (RR3-15). He has severe visual impairment (bilateral optic atrophy) and left temporal lobe epilepsy with severe developmental delay.

Conclusion: These cases expand our knowledge of the clinical phenotype associated with SOX3 duplication in boys. Array CGH can readily identify this genetic basis and permit appropriate counselling.

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