ESPE Abstracts

Introduction: SOFT-syndrome (#MIM 614783) is a rare condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis caused by POC1A gene mutations. Moreover, severe insulin resistance (IR) and metabolic disorders may also accompany. Hereby, we report two-patients with SOFT-syndrome, who had severe short stature and IR, with a novel POC1A mutation.

Case Report: Patient 1 (P1), a 16-month old girl and Patient 2 (P2), a 32-month old boy were referred with growth retardation. P1 was born at full-term to consanguineous parents, and P2 was born at 35th gestational week (GW) to unrelated parents. Both of them were born SGA. Their anthropometric measurements and physical examination findings at referral are shown in the Table. Laboratory tests for chronic and metabolic diseases were normal in both patients. In P1, central hypothyroidism was detected, sella MRI was normal; there was no adrenal insufficiency and LT4 (12.5 μg/day) was started. P2 had subclinical central hypothyroidism and no treatment was needed. At follow-up, growth velocities (GV) were low in both patients. Growth hormone (GH) stimulation tests were performed and responses were insufficient. GH treatment was started in P1 and P2 with doses of 42 and 27.5 μg/kg/day, respectively. Both patients required dose adjustments for high IGF-1-levels (mean IGF-1-SDS: 5.7&5.6, respectively). On GH treatment, insulin-levels were also high. OGTT was performed. While P1 had impaired glucose tolerance (2nd-hour-glucose: 163 mg/dl) and severe IR (total-insulin: 2600μU/ml), P2 had only severe IR (total-insulin>2700μU/ml). Additionally, hyperlipidemia was remarkable in P1. While P1 receieved both of metformin and atorvastatin, P2 receieved only metformin. As puberty progresses, GV decreased and GH treatment was discontinued at the 4th-year in P1. In P2, the change in height SDS was better than P1, therefore it has been continued in P2. Last clinical findings of patients are detailed in the Table. WES analysis revealed a novel homozygous mutation (p.Leu244Pro) in the POC1A gene in both patients.

Conclusion: A novel mutation in the POC1A gene was detected by WES analysis, which explained primordial dwarfism, dysmorphic findings and severe IR in both patients. Unlike the literature, we observed a partial improvement on height SDS in our patients (even in P1, until puberty) were with GH therapy. High IGF-1 levels on GH treatment were also associated with IR. It was also speculated; hyperinsulinemia may also have contributed to the increase in height SDS during the prepubertal period.