Endocrine Abstracts

Background: The term “neuro-cardio-facial-cutaneous (NCFC) syndrome” describes a group of phenotypically overlapping syndromes that result from germline mutations in genes of the RAS-MAPKinase pathway. This pathway plays a role in growth factor signalling and short stature is a consistent feature of NCFC syndromes. This diagnostic group includes Noonan syndrome (NS) and cardio-facio-cutaneous (CFC) syndrome. Growth hormone (GH) has been used with good effect in NS. To our knowledge the effect of GH in CFC has yet to be reported.

Case Report: A female infant was born at term, birth weight SDS −0.34, following a pregnancy complicated by polyhydramnios. She was dysmorphic (posteriorly rotated low set ears, high forehead, depressed nasal bridge, antimongoloid slant of palpebral fissures). Cardiac assessment identified pulmonary artery branch stenosis and minor atrioseptal defect. A clinical diagnosis of NS was made. At 9.9yrs of age her height SDS was −3.15, bone age 9.2yrs, serum IGF1 12 nmol/l (normal range (NR) 15–101) and peak GH response to glucagon was 10.4 mU/l. At this time the phenotype was more consistent with CFC than NS. The diagnosis was confirmed by the identification of a BRAF gene mutation (c.770A>G). Treatment with GH (0.025 mg/kg/day) was introduced. After 4 months serum IGF1 was 34.2 nmol/l and IGFBP−35.8 mg/l (NR 0.8–3.4). GH dose was increased after 4 months to 0.035 mg/kg/day and after 8 months to 0.045 mg/kg/day. There has been no change in cardiac appearance or function and no reported adverse effects of GH therapy. 13 months after starting GH the patient has gained 0.6SD in height.

Conclusion: The growth response to GH treatment observed in this patient is similar to that reported in children with NS and less than might be expected given the biochemical features of GH deficiency. The efficacy of GH in this syndrome will only be elucidated in collaborative studies of patients with CFC.