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What Is Hydrolethalus Syndrome?
Hydrolethalus Syndrome (HS) is a lethal autosomal recessive genetic disorder that is characterized by severe developmental defects in many parts of the body. Roughly 70 percent of those who have HS are stillborn, while those who are born alive survive no more than a few hours after birth. Affected individuals display severe brain defects, a highly underdeveloped jaw and polydactyly (extra fingers and/or toes). Other defective characteristics include:
- Cleft lip or palate
- Skull defects
- Ear development problems
- Eye defects
- Respiratory system defects
- Nose formation anomalies
- Club foot
- Malformed genitals
- Heart structure aberrations
HS is particularly prevalent in the Finnish population as it affects about 1 in every 20,000 Finnish infants, but it is far less common in people of other descent. In the past, it was difficult to detect the presence of HS defects in the growing fetus, but advancements in ultrasound scanning technology have enabled clinicians to detect such defects at about 13 weeks gestation, long before the affected child is born.
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What Is Known About The Genetics Of Hydrolethalus Syndrome?
In 2005, a team of Finnish human geneticists discovered a single mutation which they showed is causative of HS. Specifically, this mutation is a single base change (and, namely, a missense mutation) in the protein coding sequence of a gene that they dubbed HYLS1. This mutation causes an aspartic acid amino acid molecule which is present in healthy, or non-affected, individuals, to be changed to a glycine amino acid molecule in HS individuals. To date, no other kind of mutation to the HYLS1 gene has been discovered in humans.
The function of the normal protein product of the HYLS1 gene in humans remains unconfirmed. However, a group of U.S. scientists studied a gene that is similar to HYLS1 in the classical genetic model organism C. elegans (which is a small roundworm). They determined that the protein product of the similar C. elegans gene is required for the formation of cilia, which are hair-like structures that protrude from cells and function to move liquid over the outer cell surface. Based on these studies, it is hypothesized that the protein encoded by normal human HYLS1 also is needed for cilia formation, and therefore that the absence of functioning cilia is the culprit cause of the defects seen in HS individuals. More studies will be needed, however, to confirm this hypothesis.
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A Final Word About Hydrolethalus Syndrome
HS is a devastating disorder and once inherited, its lethal consequence seemingly cannot be avoided. For those who are not of Finnish descent, the odds of having a child that is inflicted with HS are extremely low. However, because between 1.1 and 2.5 percent of the Finnish population are carriers of the mutation known to cause HS, couples of Finnish decent may wish to consult a genetic counselor and perhaps undergo genetic testing prior to starting a family.
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A. Dammerman et al., The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia function, Genes & Development 23:2046-2059 (2009). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751977/
H. Honkala et al., Unraveling the disease pathogenesis behind the lethal hydrolethalus syndrome revealed multiple changes in molecular and cellular level, PathoGenetics (2009). http://www.pathogeneticsjournal.com/content/2/1/2
L. Mee et al., Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1, Human Molecular Genetics 14:1475-1478 (2005). http://hmg.oxfordjournals.org/content/14/11/1475.long
R. Salonen and R. Herva, Hydrolethalus Syndrome, Journal of Medical Genetics 27:756-759 (1990). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1017280/pdf/jmedgene00050-0028.pdf