Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-05-12 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonym: Salonen-Herva-Norio syndrome.

Definition: This syndrome is characterized by multiple developmental defects of fetus as polydactyly (postaxial in the hands and preaxial in the feet), central nervous system malformation such as hydrocephalus and absent midline structures of the brain, micrognathia, limb anomalies and several other abnormalities, mostly in the midline structures.

Incidence: It is approximately 1 in 20000. Parents often have some ancestry in an eastern region of Finland where the syndrome was described, for the first time, in 1981. Outside of this subgroup, the incidence is very rare.

Etiology: Autosomal recessive lethal malformation syndrome.

Diagnosis: The findings of massive hydrocephalus, encephalocele, micrognathia, polydactyly (in particular, a duplicated big toe), syndactyly, cardiac malformation, clubfeet and polyhydramnios is very suggestive of the diagnosis. Other findings include cleft lip/palate, lung hypoplasia, and endocardial cushion defects. Especially in families where there has been a previously affected fetus, ultrasound diagnosis can be made in the 11th week of gestation.

Genetic anomalies: It is caused by a missense mutation in a novel gene HYLS1.

Differential diagnosis: Other midline malformation syndromes including:Pallister-Hall, Smith-Lemli-Opitz, pseudo-trisomy 13, oral facial-digital syndrome, some skeletal dysplasias such as the short rib-polydactyly syndromes and campomelic dysplasia, hard to distinguish from Hydrolethalus, Meckel syndrome, characterized by polydactyly and central nervous system anomalies too (cephalocele instead of hydrocephaly) but adds cystic kidneys, acrocallosal syndrome, that shows severe mental retardation, agenesis or hypoplasia of the corpus callosum, polydactyly of fingers and toes, and anencephaly besides other midline defects.

Prognosis: Aside from an anecdotal survival of more than a few months, neonatal death is the rule

Management: Termination of pregnancy can be offered before viability. Standard prenatal care is not altered when continuation of the pregnancy is chosen.

References:
1: Mee L, Honkala H, Kopra O et al. Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1. Hum Mol Genet. 2005 Jun. 1; 14(11):1475-88. Epub 2005 Apr. 20.
2: Chan BC, Shek TW, Lee CP. First-trimester diagnosis of hydrolethalus syndrome in a Chinese family. Prenat Diagn. 2004 Aug; 24(8):587-90.
3: Shotelersuk V, Punyavoravud V, Phudhichareonrat S, Kukulprasong A.
An Asian girl with a "milder" form of the Hydrolethalus syndrome. Clin Dysmorphol. 2001 Jan; 10(1):51-5.
4: Christensen B, Blaas HG, Isaksen CV, Roald B, Orstavik KH.
Sibs with anencephaly, anophthalmia, clefts, omphalocele, and polydactyly:
hydrolethalus or acrocallosal syndrome? Am J Med Genet. 2000 Mar 20;91(3):231-4.
5: Visapaa I, Salonen R, Varilo T, Paavola P, Peltonen L. Assignment of the locus for hydrolethalus syndrome to a highly restricted region on 11q23-25. Am J Hum Genet. 1999 Oct; 65(4):1086-95.
6: De Ravel TJ, van der Griendt MC, Evan P, Wright CA. Hydrolethalus syndrome in a non-Finnish family: confirmation of the entity and early prenatal diagnosis. Prenat Diagn. 1999 Mar;19(3):279-81.
7: Norgard M, Yankowitz J, Rhead W, Kanis AB, Hall BD. Prenatal ultrasound findings in hydrolethalus: continuing difficulties in diagnosis. Prenat Diagn. 1996 Feb; 16(2):173-9.