Growth hormone treatment for short stature associated with duplication of the NSD1 Sotos syndrome gene

Abstract

<jats:title>Summary</jats:title> <jats:p><jats:italic>NSD1</jats:italic> deletions are associated with the Sotos syndrome, a syndrome of overgrowth in childhood without evidence of endocrine disturbance. Duplications involving the <jats:italic>NSD1</jats:italic> gene have been reported to be associated with a ‘reverse Sotos syndrome’ phenotype, characterised by short stature, microcephaly, dysmorphic features and developmental delay. A 2-year-old girl with short stature, dysmorphic features and developmental delay was found to have duplication of 5q32.2–5q32.3, which includes the <jats:italic>NSD1</jats:italic> gene. Growth hormone stimulation testing was normal. Growth hormone therapy was initiated at 5 years of age due to severe short stature and growth failure, with height 3.35 standard deviations (SDS) below the median. Growth velocity increased markedly, by +4.91 SDS in the first year of treatment. At the time of last follow-up at 9 years and 11 months, she had achieved a height within 1 SDS of the median. This is the first report of growth hormone therapy for the short stature associated with duplication of the <jats:italic>NSD1</jats:italic> gene, showing that despite normal pituitary function, exogenous growth hormone can dramatically improve linear growth.</jats:p> <jats:sec> <jats:title>Learning points</jats:title> <jats:list list-type="disc"> <jats:list-item> <jats:p>Sotos syndrome is a disorder of childhood overgrowth caused by <jats:italic>NSD1</jats:italic> deletions.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Duplications involving <jats:italic>NSD1</jats:italic> cause a ‘reverse Sotos syndrome’ phenotype characterised by short stature and microcephaly.</jats:p> </jats:list-item> <jats:list-item> <jats:p>The contrasting phenotypes of <jats:italic>NSD1</jats:italic> deletions and duplications suggest a dose effect.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Stimulated growth hormone secretion is normal in children with <jats:italic>NSD1</jats:italic> deletions and duplications.</jats:p> </jats:list-item> <jats:list-item> <jats:p>Growth hormone therapy can be very effective in children with <jats:italic>NSD1</jats:italic> duplications, comparable to the response seen in severe growth hormone deficiency.</jats:p> </jats:list-item> </jats:list> </jats:sec>