TITLE:
Three Affected Siblings in a Consanguineous Family with ECEL1-Related Distal Arthrogryposis Type 5D: Intrafamilial Phenotypic Variability—A Case Report
AUTHORS:
Luay Abdalwahab, Somar Alhourany, Nuha Al Zaabi, Ahmed Adnan, Hussein Eleimy, Olfat Al Zaabi, Reem Mahmoud, Mohamed Ali Kasem, Mohammed Allam, Ahmed Shehada, Marwa Fatima, Ribal Kasem, Mena Ayad, Sumayah Alnuami, Yasser El Gohary
KEYWORDS:
Distal Arthrogryposis Type 5D, ECEL1, Congenital Contractures, Genu Recurvatum, Ptosis, Consanguinity, Intrafamilial Variability, Genetic Counseling
JOURNAL NAME:
Open Access Library Journal,
Vol.13 No.9,
September
15,
2026
ABSTRACT: 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.