Three Affected Siblings in a Consanguineous Family with ECEL1-Related Distal Arthrogryposis Type 5D: Intrafamilial Phenotypic Variability—A Case Report

Distal arthrogryposis type 5D (DA5D) is a rare autosomal recessive congenital contracture disorder caused by biallelic variants in ECEL1. We describe a consanguineous family with three affected brothers showing a highly concordant DA5D phenotype with variable clinical severity. The index patient was a 3-month-old male infant with bilateral genu recurvatum, adducted thumbs, bilateral hip flexion contractures, congenital ptosis, micrognathia, high-arched palate, cryptorchidism, and mild facial dysmorphism. Molecular genetic testing in all three affected siblings identified the same homozygous ECEL1 variant, NM_004826.4:c.104del, p.(Pro35ArgfsTer168), classified by the diagnostic laboratory as likely pathogenic. In the available laboratory report, the deletion was shown to disrupt the translational reading frame and was reported at a gnomAD allele frequency of 0.012%, with no homozygous individuals reported at the time of testing. Across the three siblings, the most consistent manifestations were congenital knee extension deformity/genu recurvatum, thumb adduction, hip involvement, ptosis, and craniofacial abnormalities. The older siblings had greater orthopedic morbidity, including hip dislocation requiring surgery, and one had more extensive upper-limb contractures, pterygia, and developmental-language delay. The shared homozygous ECEL1 variant, together with the recurrent characteristic phenotype, supports familial segregation of ECEL1-related DA5D among the three affected brothers and illustrates intrafamilial phenotypic variability. Early recognition, multidisciplinary orthopedic and ophthalmologic care, rehabilitation, and genetic counseling are important.