SERKAL syndrome

SERKAL syndrome (SEx Reversion, Kidneys, Adrenal and Lung dysgenesis syndrome) is an extremely rare, lethal autosomal recessive disorder caused by mutations in the WNT4 gene. This condition is characterized by female-to-male sex reversal in 46,XX individuals, meaning that genetically female fetuses develop male or ambiguous external genitalia. The syndrome affects multiple organ systems, with key features including bilateral renal agenesis (absence of both kidneys), adrenal hypoplasia or agenesis (underdevelopment or absence of the adrenal glands), and lung dysgenesis (severely underdeveloped lungs). The condition was first described in 2008 in consanguineous families. Affected fetuses typically present with a constellation of severe developmental anomalies that are incompatible with life, and the syndrome is considered lethal in the prenatal or neonatal period. Additional features may include cardiac defects and other visceral malformations. Because of the severity and lethality of the condition, affected pregnancies often result in stillbirth or death shortly after birth. There is currently no treatment for SERKAL syndrome. Management is limited to supportive care and genetic counseling for affected families. Prenatal diagnosis may be possible through ultrasound detection of the characteristic malformations combined with molecular genetic testing of the WNT4 gene. Carrier testing and preimplantation genetic diagnosis may be offered to families with a known pathogenic variant.

Common questions about SERKAL syndrome