A New Case of Lethal Congenital Contracture Syndrome Type 3 With Hyperinsulinism and Optic Atrophy
4 affiliations
- 1The Ruth and Bruce Rappaport Faculty of Medicine Technion‐Israel Institute of Technology Haifa Israel
- 2Genetics Institute, Rambam Health Care Center Haifa Israel
- 3The Hebrew University of Jerusalem Jerusalem Israel
- 4Pediatric Endocrinology and Diabetes Unit Rambam Health Care Center Haifa Israel
Abstract
Lethal congenital contracture syndrome 3 (LCCS3, MIM #611369) is a rare autosomal recessive neuromuscular disorder caused by biallelic loss‐of‐function (LOF) variants in PIP5K1C, reported in only two families to date. It typically presents with severe fetal akinesia, arthrogryposis multiplex congenita, and perinatal lethality due to respiratory insufficiency case. Herein, we report a new case with survival beyond birth. Prenatal findings included clubfeet with preserved amniotic fluid volume and fetal movements. The infant was delivered by cesarean section at 37 + 7 weeks following breech presentation and developed respiratory distress requiring 14 days of ventilatory support. Physical examination revealed bilateral talipes equinovarus, flexion contractures of the knees, restricted hip mobility, clenched hands with flexion contractures of the third and fourth fingers, and hyperextension of the second and fifth fingers. Neurologically, he had encephalopathy, profound hypotonia with a frog posture, and abnormal neonatal reflexes with a discontinuous background pattern on cerebral function monitoring. Additional observed features were bilateral optic atrophy and hyperinsulinemic hypoglycemia responsive to Diazoxide. Trio genome sequencing identified a homozygous pathogenic splice‐site variant in PIP5K1C (c.1127+1G>A, NM_012398.3). The infant died at 6 months from multisystemic failure. Further studies are warranted to elucidate the pathomechanisms underlying the PIP5K1C defect and its phenotypic consequences.
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BibTeX
@article{moady2026case,
title = {{A New Case of Lethal Congenital Contracture Syndrome Type 3 With Hyperinsulinism and Optic Atrophy}},
author = {Tameemi Abdalla Moady and Hadar Hulin Ma'ayan and Michal Cohen and Karin Weiss},
journal = {Clinical Genetics},
year = {2026},
month = sep,
doi = {10.1111/cge.70231},
url = {https://doi.org/10.1111/cge.70231},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A New Case of Lethal Congenital Contracture Syndrome Type 3 With Hyperinsulinism and Optic Atrophy
AU - Tameemi Abdalla Moady
AU - Hadar Hulin Ma'ayan
AU - Michal Cohen
AU - Karin Weiss
PY - 2026
DA - 2026/09/16
JO - Clinical Genetics
DO - 10.1111/cge.70231
UR - https://doi.org/10.1111/cge.70231
AB - Lethal congenital contracture syndrome 3 (LCCS3, MIM #611369) is a rare autosomal recessive neuromuscular disorder caused by biallelic loss‐of‐function (LOF) variants in PIP5K1C, reported in only two families to date. It typically presents with severe fetal akinesia, arthrogryposis multiplex congenita, and perinatal lethality due to respiratory insufficiency case. Herein, we report a new case with survival beyond birth. Prenatal findings included clubfeet with preserved amniotic fluid volume and fetal movements. The infant was delivered by cesarean section at 37 + 7 weeks following breech presentation and developed respiratory distress requiring 14 days of ventilatory support. Physical examination revealed bilateral talipes equinovarus, flexion contractures of the knees, restricted hip mobility, clenched hands with flexion contractures of the third and fourth fingers, and hyperextension of the second and fifth fingers. Neurologically, he had encephalopathy, profound hypotonia with a frog posture, and abnormal neonatal reflexes with a discontinuous background pattern on cerebral function monitoring. Additional observed features were bilateral optic atrophy and hyperinsulinemic hypoglycemia responsive to Diazoxide. Trio genome sequencing identified a homozygous pathogenic splice‐site variant in PIP5K1C (c.1127+1G>A, NM_012398.3). The infant died at 6 months from multisystemic failure. Further studies are warranted to elucidate the pathomechanisms underlying the PIP5K1C defect and its phenotypic consequences.
SN - 0009-9163
SN - 1399-0004
ER -