A New Case of Lethal Congenital Contracture Syndrome Type 3 With Hyperinsulinism and Optic Atrophy.
Tameemi Abdalla Moady, Hadar Hulin Ma'ayan, Michal Cohen et al.
✦ AI-curated · Sources linked
Case in brief
An infant with prenatal clubfeet, preserved amniotic fluid and fetal movements was born at 37 + 7 weeks after breech presentation. He developed respiratory distress requiring 14 days of ventilatory support and had multiple limb contractures, encephalopathy, profound hypotonia and abnormal neonatal reflexes. Examination also showed bilateral optic atrophy; hyperinsulinemic hypoglycemia responded to diazoxide. Trio genome sequencing identified a homozygous pathogenic PIP5K1C splice-site variant (c.1127+1G>A), supporting a diagnosis of LCCS3. He died at 6 months from multisystemic failure.
What made this case unusual
Unlike the typically perinatally lethal presentation described for LCCS3, this infant survived beyond birth; bilateral optic atrophy and diazoxide-responsive hyperinsulinemic hypoglycemia were additional findings.
Diagnostic / clinical pearl
In an infant with congenital contractures and severe hypotonia, a homozygous pathogenic PIP5K1C variant can establish LCCS3 even when prenatal fetal movements and amniotic fluid volume are preserved.
Why it matters
The optic atrophy and hyperinsulinemic hypoglycemia in this case broaden the reported clinical features associated with PIP5K1C-related LCCS3; their underlying mechanisms remain to be elucidated.