Summary
Hydrolethalus syndrome was first described by Finish authors, who separated hydrolethalus from Meckel syndrome, both syndromes sharing several characteristics: autosomal recessive inheritance, lethality, central nervous system (CNS) malformation, and polydactyly. Unlike Meckel syndrome, hydrolethalus does not show cystic kidney and liver and the CNS anomaly is hydrocephalus, not encephalocele. Pregnancy is characterized by hydramnios (often severe) and by preterm delivery when pregnancy evolves spontaneously. The minimal diagnostic criteria in fetuses or newborns include hydrocephalus, micrognathism and polydactyly. The brain hemispheres lie separated from each other with lateral ventricles opened medially into a fluid-filled space where corpus callosum and septum pellucidum are absent and cerebellar vermis absent or hypoplastic. A midline defect in the occipital bone dorsal to the foramen magnum is observed, resulting in a keyhole-shaped defect. Polydactyly is postaxial in the hands and preaxial in the feet. Feet are clubbed. The mandible is always small and the nose poorly formed; eyes are deep-set. About half patients have large septal cardiac defect. Stenosis of the airway (larynx, trachea or bronchus) and abnormal genitalia (including uterus duplex in females and ectopic testis in males), abnormal lobation of the lungs are also found. Holoprosencephaly or anencephaly has been observed in isolated cases. Prenatal diagnosis by ultrasonography can be already carried out at the end of first trimester when a previous pregnancy was affected. In absence of index case, reliable differential diagnosis from other Mendelian midline multiple malformation syndromes like Pallister-Hall, pseudo-trisomy 13, oro-facio-digital type IV or VI, Joubert syndromes, as well as severe form of Smith Lemli Opitz is difficult. Prevalence at birth is around 1:20,000 in Finland, where the 56 cases reported in the literature were born. Less than 10 cases were reported by non-Finnish authors. Stillbirth or neonatal death is the rule but one paper reported a case still living at more than 6 weeks of age, and another a case who died at 7 months. Hydrolethalus syndrome locus was assigned to 11q23-q25 in Finnish families. The critical locus could be localized between markers D11S933 and D11S934. Genealogic studies performed in families affected by hydrolethalus revealed no regional clustering, suggesting a relatively early introduction of the disease mutation into the Finnish population and the spreading of the mutation with the inhabitation of the late-settlement area. *Author : Orphanet (April 2003)*.
