Small SOX3 duplications can cause hypopituitarism and neural tube defects

medwireNews: A case series illustrates the highly variable phenotypes of patients with congenital hypopituitarism caused by SOX3 duplication, and strengthens the association with neural tube defects.

“Array [comparative genomic hybridization] should be considered to investigate for SOX3 duplication in males with intellectual disability and [congenital hypopituitarism] with or without midline central nervous system defects”, write Ritika Kapoor (King’s College Hospital NHS Foundation Trust, London, UK) and study co-authors.

All five patients (all male and unrelated) in their study had Xq27.1 duplications, which includes SOX3. Two Xq27.1 duplications were maternally derived, two were de novo and one was unknown. The duplication sizes ranged from 11 Mb down to just 323.8 kb, and four patients had duplications that were smaller than the smallest previously reported duplication of 685.6 kb.

Three of the patients presented at less than a week old, with features including jaundice, hypoglycaemia, failure to thrive, micropenis, small testes and spina bifida. The fourth presented at 4.8 years with short stature and developmental delay and the fifth at 14.6 years with short stature and pubertal delay.

The most common features were pituitary hormone deficiencies, with growth hormone (GH) deficiency found in four patients; small genitalia, observed in four patients; and intellectual disability, which was severe in two patients, moderate in one and mild with one, with the fifth patient too young to assess at the time of the report.

“This series emphasizes the associated variable clinical phenotype [of SOX3 duplication], highlighting the wide spectrum ranging from isolated GH deficiency to panhypopituitarism”, write the researchers in Hormone Research in Paediatrics.

They highlight that only small duplications were found in four of their patients, yet one presented in infancy with panhypopituitarism, anterior pituitary hypoplasia and an ectopic posterior pituitary, demonstrating “that even a small SOX3 microduplication is enough to severely disrupt hypothalamic-pituitary development”.

Of note, one patient, who presented with spina bifida and small genitalia, had a normal initial endocrine evaluation. However, he showed poor growth, with a height standard deviation score of –2.81 at the age of 0.25 years, and the study authors say that he “remains under regular surveillance for growth and endocrine function.”

Kapoor and team also highlight the link between SOX3 duplication and neural tube defects, previously reported by other researchers and strengthened by the current case series in which two patients had spina bifida.

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group

Hormone Res Paediatr 2020; doi:0.1159/000503784
Martin Savage
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