ESPE Abstracts

Background: IGFR1 gene plays a crucial role in growth and glucose metabolism. IGF1R mutations account for approximately 10% of children born SGA with no catch-up growth. rhGH therapy has been reported moderately effective in stimulating growth of children with heterozygous IGF1R mutation. To date, no data are available about the efficacy of rhGH in patients with homozygous mutations.

Case report: We describe a 4 years-old girl referred for severe pre- and postnatal growth retardation. Height 77 cm (-6 SDS), weight 6.5 kg (-11 SDS), OFC 42 cm (< -2 SDS), pubertal Tanner stage I. She was born at 36 weeks of gestational age by consanguineous parents with a birth weight of 950 g (–4.12 SDS), length 39 cm (–3.20 SDS), OFC 24.5 cm (–5.53 SDS) associated with cardiac and CNS defects, atrophic left iris, bilateral sensorineural hearing loss and progeroid features with triangular face, sparse scalp hair, low set ears, hypoplastic alae nasi, micrognathia. Karyotype and arrayCGH were normal. Whole Exome Sequencing showed homozygous c.2201G>T missense mutation in the exon 10 of IGF1R gene, never reported in literature. Parents were both carriers of monoallelic IGF1R mutation with a mild phenotype of short stature, in particular mother’s height was 151 cm (-2.3 SDS) and father’s height was 159 cm (-2.2 SDS). Paternal and maternal grandmothers had type 2 diabetes history. Proband’s IGF1 level was 422 ng/ml (+2 SDS) and glucose metabolism (baseline glucose and insulin, OGTT, HbA1c) was normal. rhGH therapy was started at the dose of 42 mg/kg/day. The height gain was +1 SDS in 2 years of therapy. However, after 2 yrs rhGH therapy was stopped for impaired glucose tolerance. OGTT 2 hours-postload glycemia 162 mg/dl and HbA1c 48 mmol/mol. At last visit (age 8 years and 6 months), height was 97.5 cm (-6.3 SDS) and weight 11 kg (-8.5 SDS) with a height gain of -3.2 SDS in 3 years off-therapy.

Conclusion: We first report a case of homozygous IGF1R mutation treated with rhGH. Our findings suggest that rhGH therapy may partially reduce the height deficit but can affect glucose homeostasis.