Meier–Gorlin syndrome due to a recurrent DONSON variant in a Turkish family: first report of thumb aplasia and long-term growth data

Abstract Objectives Meier–Gorlin syndrome (MGORS) is a rare primordial dwarfism characterized by microtia, patellar hypoplasia/aplasia, and short stature. Additional features may include skeletal, respiratory, urogenital, and endocrine abnormalities. 13 genes have been implicated, with DONSON , essential for replication fork stability and intra–S phase checkpoint activation, being the most recently identified. Only six patients with DONSON -related MGORS have been reported. This study expands the phenotype by presenting long-term follow-up and prenatal data in two affected siblings. Case presentation The index patient, a 10-year-old male, had short stature, microcephaly, microtia, craniofacial features, hearing loss, patellar aplasia, and genitourinary anomalies. Despite an early growth delay, his height progressively improved without intervention. Whole-exome sequencing revealed a homozygous pathogenic c.631C>T p.(Arg211Cys) variant in DONSON (NM_017613.3). Following genetic counseling, the family declined prenatal testing in a subsequent pregnancy complicated by intrauterine growth restriction. The newborn female sibling carried the same variant and displayed DONSON -related MGORS features, including the first reported case of thumb aplasia. Additional findings in the family included renal hypoplasia, 2–4 toe syndactyly, and hypospadias. Conclusions This is the third report of DONSON c.631C>T p.(Arg211Cys) in Turkish patients. While the recurrence in the same population suggests a founder effect, haplotype–based analysis is required. Thumb aplasia expands the known phenotype of DONSON -related MGORS, and the observed moderate course of growth retardation offers prognostic value. These findings highlight the importance of including DONSON in MGORS gene panels, considering population-specific variants, and systematically documenting rare phenotypic features to improve diagnosis, follow-up, and genetic counseling.