Hydrolethalus

Hydrolethalus syndrome (HLS), also known as hydrolethalus syndrome type 1 or Salonen-Herva-Norio syndrome, is a severe autosomal recessive developmental disorder that is almost invariably lethal in the prenatal or early neonatal period. It was first described in the Finnish population, where it is more prevalent due to a founder effect. The condition is caused by mutations in the HYLS1 gene on chromosome 11q24.2, which encodes a protein involved in ciliogenesis and is critical for normal embryonic development. Hydrolethalus syndrome is characterized by severe central nervous system malformations, including hydrocephaly and absence or malformation of midline brain structures (such as absent septum pellucidum and agenesis of the corpus callosum). A hallmark feature is a "keyhole" defect of the occipital bone. Other major findings include polydactyly (typically postaxial in the hands and preaxial in the feet, with a characteristic hallux duplex), micrognathia, congenital heart defects (such as atrioventricular canal defects or ventricular septal defects), and abnormal lobation of the lungs. Affected fetuses may also present with clubfeet, cleft lip or palate, and airway anomalies including abnormalities of the larynx and trachea. The prognosis is extremely poor, with most affected pregnancies resulting in stillbirth or death within the first days of life. Polyhydramnios is frequently observed during pregnancy. There is no curative treatment for hydrolethalus syndrome. Management is limited to supportive and palliative care. Prenatal diagnosis is possible through ultrasound detection of the characteristic malformations and through molecular genetic testing when the familial mutation is known. Genetic counseling is recommended for affected families, as carrier parents have a 25% recurrence risk with each pregnancy.

Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

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Common questions about Hydrolethalus