SLC26A2-Related Atelosteogenesis

Excerpt

Clinical characteristics: Clinical features of SLC26A2-related atelosteogenesis include rhizomelic limb shortening with normal-sized skull, hitchhiker thumbs, small chest, protuberant abdomen, cleft palate, and distinctive facial features (midface retrusion, depressed nasal bridge, epicanthus, micrognathia). Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. SLC26A2-related atelosteogenesis is usually lethal at birth or shortly thereafter due to pulmonary hypoplasia and tracheobronchomalacia. However, it exists in a continuous phenotypic spectrum with SLC26A2-related diastrophic dysplasia, and long-term survivors have been reported.

Diagnosis/testing: The diagnosis of SLC26A2-related atelosteogenesis is established in a proband with characteristic clinical, radiologic, and histopathologic features and biallelic pathogenic variants in SLC26A2 identified by molecular genetic testing.

Management: Treatment of manifestations: There is no specific treatment currently available, and the aim of therapy (supportive versus palliative) will depend on clinical status and respiratory prognosis of the individual patient.

Genetic counseling: SLC26A2-related atelosteogenesis is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an SLC26A2 pathogenic variant, each sib of a proband with SLC26A2-related atelosteogenesis 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. Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing for a pregnancy at increased risk are possible if both pathogenic variants in the family are known. Ultrasound examination early in pregnancy is a reasonable complement or alternative to molecular genetic prenatal testing.