EXOC6B-Related Spondyloepimetaphyseal Dysplasia with Joint Laxity

Excerpt

Clinical characteristics: EXOC6B-related spondyloepimetaphyseal dysplasia with joint laxity (EXOC6B-SEMD-JL) is characterized by multiple joint dislocations, joint laxity, genu valgum, short stature, and skeletal dysplasia. Joint dislocations of the hips and knees are present at birth in all individuals reported to date. Dislocations can also occur at the elbows, wrists, ankles, and patellae. Growth deficiency develops postnatally. Short neck, scoliosis, kyphosis, and hyperlordosis are reported. The fingers are slender (leptodactyly). Radiographic manifestations include delayed carpal/tarsal bone ossification, gracile short tubular bones, metaphyseal and epiphyseal dysplasia, slender ribs, and spondylar dysplasia (irregular vertebral end plates, narrow interpedicular distance of the lumbar spine, and modest platyspondyly) with age-dependent evolution.

Diagnosis/testing: The diagnosis of EXOC6B-SEMD-JL is established in a proband with characteristic clinical and radiographic features and biallelic pathogenic variants in EXOC6B identified by molecular genetic testing.

Management: Treatment of manifestations: Surgical interventions for joint dislocations to improve mobility; wheelchair and walking aids as needed; physical therapy and orthopedic interventions as needed for scoliosis and kyphosis.

Surveillance: Annual assessment of joints by a rheumatologist or orthopedic surgeon; annual clinical and radiographic assessment for scoliosis and/or kyphosis.

Genetic counseling: EXOC6B-SEMD-JL is inherited in autosomal recessive manner. If both parents are known to be heterozygous for an EXOC6B pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the EXOC6B pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.