A novel mutation of the insulin receptor gene in a preterm infant with Donohue syndrome and heart failure

作者：Nobile Stefano^*; Semple Robert K; Carnielli Virgilio P

来源：Journal of Pediatric Endocrinology & Metabolism, 2012, 25(3-4): 363-366.

DOI：10.1515/jpem-2011-0448

• Donohue syndrome
• heart failure
• insulin receptor gene
• preterm

Donohue syndrome (DS) is a rare autosomal recessive condition caused by mutations in the gene encoding the insulin receptor. It is characterised by severe metabolic and endocrine derangement, prenatal and postnatal linear growth impairment, soft tissue overgrowth, and poor development of adipose tissue and muscle. Causes of death, which is often within the first year of life, include intercurrent infection and, in some cases, heart failure. Management is currently based on case reports and very small case series only, and no formal guidelines or recommendations exist. We describe a preterm infant who had typical features of DS but who later developed hypertrophic cardiomyopathy with heart failure leading to death at 10 weeks old. Molecular genetic analysis revealed compound heterozygosity for the previously reported p.Arg890X nonsense mutation and the novel p.Tyr818Cys missense mutation in the INSR gene. Tyrosine 818 falls in an exquisitely conserved residue of the alpha beta fibronectin domain of the insulin receptor, whose structure and function are much less well understood than other parts of the receptor. We discuss management options for DS, including the therapeutic dilemma around whether recombinant human insulin-like growth factor 1, one of the few available treatments for the syndrome, may exacerbate hypertrophic cardiomyopathy and cardiac failure.

• 出版日期2012-4