Differences in sex development

Gene: WNT4

Red List (low evidence)

PMID: 40992710 Hernández-García et al., 2025
Study identified a consanguineous Afghan family with SERKAL syndrome. Parents were second cousins, healthy. First pregnancy was complicated by oligohydramnios and the male fetus was found to have unilateral renal agenesis. He died shortly after delivery. Their second pregnancy resulted in a miscarriage at 8 weeks gestation.
During the third pregnancy, ultrasound examination at 21 weeks gestation was suggestive of renal agenesis - pregnancy was terminated. Autopsy showed contractures, bilateral agenesis of the diaphragm, pulmonary hypoplasia, bilateral renal hypoplasia with cystic dysplasia, agenesis of the right adrenal, and marked hypoplasia of the left adrenal. Clinical trio exome showed the fetus was homozygous for WNT4: c.872C>G, p.(Thr291Arg)

PMID: 18179883 Mandel et al., 2008
Described a consanguineous kindred in which a pair of siblings and their spouses had three pregnancies terminated at 19-24 weeks gestation due to ultrasound findings suggestive of renal agenesis. Autopsies performed on these fetuses revealed largely overlapping features that included 46,XX sex reversal and dysgenesis of the kidneys, adrenals, and lungs. Other reported anomalies included VSD and pulmonary artery stenosis (n = 1), congenital diaphragmatic hernia (n = 1), and orofacial clefting (n = 2). A homozygous WNT4 variant c.341C>T, p.(Ala114Val) was identified as causal.
Sources: Literature

Created: 2 Nov 2026, 5 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
SERKAL syndrome, OMIM:611812; SERKAL syndrome, MONDO:0012734; 46,XX Sex reversal with dysgenesis of kidneys Adrenals and lungs

Publications

• 18179883
• 40992710