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Open access

George Stoyle, Siddharth Banka, Claire Langley, Elizabeth A Jones and Indraneel Banerjee

Summary

Wiedemann–Steiner Syndrome (WSS) is a rare condition characterised by short stature, hypertrichosis of the elbow, intellectual disability and characteristic facial dysmorphism due to heterozygous loss of function mutations in KMT2A, a gene encoding a histone 3 lysine 4 methyltransferase. Children with WSS are often short and until recently, it had been assumed that short stature is an intrinsic part of the syndrome. GHD has recently been reported as part of the phenotypic spectrum of WSS. We describe the case of an 8-year-old boy with a novel heterozygous variant in KMT2A and features consistent with a diagnosis of WSS who also had growth hormone deficiency (GHD). GHD was diagnosed on dynamic function testing for growth hormone (GH) secretion, low insulin-like growth factor I (IGF-I) levels and pituitary-specific MRI demonstrating anterior pituitary hypoplasia and an ectopic posterior pituitary. Treatment with GH improved height performance with growth trajectory being normalised to the parental height range. Our case highlights the need for GH testing in children with WSS and short stature as treatment with GH improves growth trajectory.

Learning points:

  • Growth hormone deficiency might be part of the phenotypic spectrum of Wiedemann–Steiner Syndrome (WSS).

  • Investigation of pituitary function should be undertaken in children with WSS and short stature. A pituitary MR scan should be considered if there is biochemical evidence of growth hormone deficiency (GHD).

  • Recombinant human growth hormone treatment should be considered for treatment of GHD.

Open access

Anna Casteràs, Jürgen Kratzsch, Ángel Ferrández, Carles Zafón, Antonio Carrascosa and Jordi Mesa

Summary

Isolated GH deficiency type IA (IGHDIA) is an infrequent cause of severe congenital GHD, often managed by pediatric endocrinologists, and hence few cases in adulthood have been reported. Herein, we describe the clinical status of a 56-year-old male with IGHDIA due to a 6.7 kb deletion in GH1 gene that encodes GH, located on chromosome 17. We also describe phenotypic and biochemical parameters, as well as characterization of anti-GH antibodies after a new attempt made to treat with GH. The height of the adult patient was 123 cm. He presented with type 2 diabetes mellitus, dyslipidemia, osteoporosis, and low physical and psychological performance, compatible with GHD symptomatology. Anti-GH antibodies in high titers and with binding activity (>101 IU/ml) were found 50 years after exposure to exogenous GH, and their levels increased significantly (>200 U/ml) after a 3-month course of 0.2 mg/day recombinant human GH (rhGH) treatment. Higher doses of rhGH (1 mg daily) did not overcome the blockade, and no change in undetectable IGF1 levels was observed (<25 ng/ml). IGHDIA patients need lifelong medical surveillance, focusing mainly on metabolic disturbances, bone status, cardiovascular disease, and psychological support. Multifactorial conventional therapy focusing on each issue is recommended, as anti-GH antibodies may inactivate specific treatment with exogenous GH. After consideration of potential adverse effects, rhIGF1 treatment, even theoretically indicated, has not been considered in our patient yet.

Learning points

  • Severe isolated GHD may be caused by mutations in GH1 gene, mainly a 6.7 kb deletion.

  • Appearance of neutralizing anti-GH antibodies upon recombinant GH treatment is a characteristic feature of IGHDIA.

  • Recombinant human IGF1 treatment has been tested in children with IGHDIA with variable results in height and secondary adverse effects, but any occurrence in adult patients has not been reported yet.

  • Metabolic disturbances (diabetes and hyperlipidemia) and osteoporosis should be monitored and properly treated to minimize cardiovascular disease and fracture risk.

  • Cerebral magnetic resonance imaging should be repeated in adulthood to detect morphological abnormalities that may have developed with time, as well as pituitary hormones periodically assessed.