ECEL1 mutation in distal arthrogryposis type 5D: A case report

Background: Arthrogryposis multiplex congenita involves joint contractures across various body parts. Distal arthrogryposis type 5D (DA5D) is a rare, autosomal recessive subtype affecting distal extremities, with symptoms like knee extension contractures, camptodactyly, overriding fingers, ulnar wrist deviation, and scoliosis.

Case: A 24-year-old pregnant woman with a second-degree relative partner had a fetus showing increased nuchal translucency (3.4 mm) and high Down syndrome risk in the first-trimester screen. Both parents were healthy and had no known family history of hereditary diseases. Genetic counselling and amniocentesis at 16 weeks revealed a segmental gain on chromosome 1p31.1 of uncertain significance, ruling out aneuploidies of chromosomes 21, 18, and 13. Later scans suggested fetal akinesia deformation sequence (FADS) with limited limb movement. Whole exome sequencing confirmed DA5D due to a novel ECEL1 5' splice site variant (c.2151 + 2T > A) inherited autosomally recessive. The couple chose pregnancy termination, with an autopsy confirming DA5D.

Conclusion: This case expands the mutational spectrum of prenatal ECEL1 gene using whole exome sequencing (WES) for fetal joint disorders, potentially helping in parental counselling and clinical decision-making.