Saul-Wilson Syndrome

Excerpt

Clinical characteristics: Saul-Wilson syndrome (SWS) is a skeletal dysplasia characterized by profound short stature, distinctive craniofacial features, short distal phalanges of fingers and toes, and often clubfoot. Early development (primarily speech and motor) is delayed; cognition is normal. Other findings can include hearing loss (conductive, sensorineural, and mixed), lamellar cataracts, and/or rod-cone retinal dystrophy. To date, 16 affected individuals have been reported.

Diagnosis/testing: The diagnosis of SWS is established in a proband with marked short stature, typical facial and skeletal features, and a heterozygous pathogenic variant in COG4 identified by molecular genetic testing. To date only two COG4 variants, both resulting in a p.Gly516Arg missense change, have been reported.

Management: Treatment of manifestations: Skeletal dysplasia or physiatry clinic (orthopedist, OT/PT/ rehabilitation specialist) to address repair of clubfoot, possible C1-C2 subluxation and/or spinal cord compression, mobility issues in those with residual foot deformities (post clubfoot repair), osteoarticular pain; standard treatment for feeding issues, speech delay, cataracts and retinal dystrophy, and hearing loss.

Surveillance: Routine follow up of growth and feeding, developmental progress and educational needs, musculoskeletal issues including mobility, osteoarticular pain, bone fragility, possible cataracts and/or retinal dystrophy, hearing loss.

Agents/circumstances to avoid: Participation in gymnastics and jumping on a trampoline until atlanto-axial instability is excluded.

Genetic counseling: SWS is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Sib recurrence has been observed in one family and is thought to result from germline mosaicism in a parent. The risk to offspring of an individual with SWS of inheriting the COG4 pathogenic variant is 50%. Once the COG4 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.