Variants in the GDF6gene, coding for growth differentiation factor 6, are associated with Klippel-Feil syndrome type 1, multiple synostoses syndrome, Leber congenital amaurosis, and microphthalmia. The spectrum of anomalies associated with GDF6variants is huge and highly variable. Most reported phenotypes are inherited in an autosomal dominant manner, although penetrance and expressivity are also highly variable. Patients with GDF6variants have been reported with skeletal phenotypes, i.e. (i) Klippel-Feil syndrome with vertebral segmentation defects frequently associated with scoliosis, rib abnormalities, and Sprengel’s deformity, (ii) Chiari malformations, (iii) multiple synostoses syndrome including carpal and tarsal fusions, (iv) ocular phenotypes (i.e. microphthalmia, coloboma, Leber congenital amaurosis or juvenile retinitis pigmentosa, glaucoma), and, most recently, (v) congenital anomalies of the kidney and urinary tract (CAKUT) such as kidney hypodysplasia or crossed fused renal ectopia in patients often additionally manifesting skeletal, ocular, or auricular anomalies.
GDF6