Geroderma Osteodysplasticum Due to a Recurrent Golgi Ras-Associated Binding (GORAB) GTPase-Binding Protein Variant: A...

Geroderma osteodysplasticum (GO) is an ultra-rare inherited connective tissue disorder. We report a retrospective case series of two Moroccan patients with geroderma osteodysplasticum carrying the same recurrent Golgi Ras-associated binding (RAB) GTPase-binding protein (GORAB) variant. Patient 1 was an 11-year-old boy who presented in January 2026, and Patient 2 was a five-year-old girl who presented in September 2024; both were born to consanguineous parents. They harbored the identical homozygous pathogenic truncating GORAB variant (NM_152281.3:c.79C>T; p.Arg27*), confirmed by targeted Sanger sequencing and clinical exome sequencing, respectively, and classified as pathogenic in ClinVar (rs770355472). One of these patients (Patient 2) had previously been reported as an isolated case. Both patients presented with the classical triad of cutaneous laxity with pseudo-aged skin, generalized joint hyperlaxity, and growth retardation. Patient 1 additionally exhibited cryptorchidism and delayed bone age. Patient 2 presented with severe factor V deficiency (<1% activity), thoracolumbar kyphoscoliosis with vertebral wedging, and a bleeding diathesis characterized by recurrent epistaxis and easy bruising. Management was primarily supportive and multidisciplinary, including clinical monitoring and treatment tailored to individual manifestations. Follow-up demonstrated persistence of the underlying connective tissue disorder with variable clinical severity but no major disease-specific complications. The identification of the identical GORAB p.Arg27* variant in two unrelated Moroccan consanguineous families raises the possibility of a founder effect warranting further population-based investigation. By comparing two phenotypically distinct patients carrying the same pathogenic variant, this report highlights the clinical variability associated with GORAB-related disease and suggests that hemostatic evaluation should be considered in patients with GO who present with a personal or family history suggestive of a bleeding disorder.