Indian patients with CHST3-related chondrodysplasia with congenital joint dislocations.

CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition.

Two Somali half-siblings with CHST3-related chondrodysplasia illustrating the phenotypic spectrum and intrafamilial variability.

Deficiency of carbohydrate sulfotransferase 3 (CHST3; also known as chondroitin-6-sulfotranferase) has been associated with a phenotype of severe chondrodysplasia and progressive spinal involvement. Recent reports indicate that affected individuals initially present with neonatal multiple joint dislocations. We describe a 14-year-old Somali patient and her 3-year-old maternal half-brother with novel homozygous CHST3 mutations. The proband presented at the age 5½ years with short stature and genua valga. Her clinical course was characterized by rapid progression of spinal deformities and large joint contractures. Her half-brother presented at birth with bilateral knee dislocation and talipes equinovarus. This report of a Somali family with CHST3-related chondrodysplasia illustrates the intrafamilial variability in phenotypic expression of this rare disorder. © 2013 Wiley Periodicals, Inc.