Tetra-Amelia Syndrome – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

Excerpt

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: Tetra-amelia syndrome is characterized by the (complete) absence of all four limbs and anomalies involving the cranium and the face (cleft lip/cleft palate, micrognathia, microtia, single naris, choanal atresia, absence of nose); eyes (microphthalmia, microcornea, cataract, coloboma, palpebral fusion); urogenital system (renal agenesis, persistence of cloaca, absence of external genitalia, atresia of vagina); anus (atresia); heart; lungs (hypoplasia/aplasia), skeleton (hypoplasia/absence of pelvic bones, absence of ribs, absence of vertebrae), and central nervous system (agenesis of olfactory nerves, agenesis of optic nerves, agenesis of corpus callosum, hydrocephalus). Affected infants are often stillborn or die shortly after birth.

Diagnosis/testing: The diagnosis of tetra-amelia syndrome can be established clinically and is usually made on routine prenatal ultrasonography. WNT3 is the only gene in which pathogenic variants are known to cause tetra-amelia syndrome. The variant detection frequency is unknown as only a limited number of families have been studied.

Management: Affected infants are often stillborn or die shortly after birth. Management of (as yet unreported) persons who survive will depend on the presence and severity of associated malformations and require the support of several medical disciplines.

Genetic counseling: Tetra-amelia syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has 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. Heterozygotes (carriers) are asymptomatic. Prenatal testing by molecular genetic testing is possible if the pathogenic variants in WNT3 have been identified in an affected family member.