Orthologs, genes in other species with common ancestral heritage, have been examined to explain the pathophysiology of HLS; a similar gene within the roundworm, Caenorhabditis elegans, is responsible for the formation of cilia. Current hypotheses place a dysfunction of cilia as the main cause of HLS defects arising from the HYLS1 mutation in humans. Differences between wild type and mutant HYLS1 have been clearly observed; the wild type form is localised to the cytoplasm, while the mutant form is localised to the nucleus and forms small clusters, suggesting that the mutant gene disrupts cellular localisation. The protein encoded by the HYLS1 mutant form is unable to carry out essential targeting of centrioles to the plasma membrane, disrupting ciliary function, which results in ciliopathy. As cilia are located in almost all cells throughout the body, cilial dysfunction causes developmental defects in a range of organs and thus the phenotype of HLS can vary greatly, though brain malformation and polydactyly are most commonly observed. Environmental
Currently, no environmental factors are known to increase the likelihood of HLS development or progression; HLS is caused only by genetic abnormalities. Pathophysiology
The pathophysiology of HLS is abnormal cilia development arising from the inability of the mutated HYLS1 gene to correctly target centrioles to the plasma membrane. Specifically, transition fibres within the transition zone, at the base of the axoneme and adjoining to the plasma membrane, lack proper development. As these structures form the cilial gate, improper development results in a loss of selectivity for protein entry into the ciliary compartment.
Ciguatera fish poisoning (CFP), also known simply as ciguatera, is a foodborne illness caused by eating reef fish whose flesh is contaminated with certain toxins. Such individual fish are said to be ciguatoxic. Symptoms may include diarrhea, vomiting, numbness, itchiness, sensitivity to hot and cold, dizziness, and weakness. The onset of symptoms varies with the amount of toxin eaten from half an hour to up to two days. The diarrhea may last for up to four days. Some symptoms typically remain for a few weeks to months. Heart difficulties such as slow heart rate and low blood pressure may also occur.The specific toxins involved are ciguatoxin and maitotoxin. They are originally made by a small marine organism, Gambierdiscus toxicus, that grows on and around coral reefs in tropical and subtropical waters. These are eaten by herbivorous fish which in turn are eaten by larger carnivorous fish. The toxins become more concentrated as they move up the food chain. The fish most often implicated include barracuda, grouper, moray eel, amberjack, sea bass, and sturgeon. Diagnosis is based on a persons symptoms together with having recently eaten fish. If a number of those who eat the same fish develop symptoms the diagnosis becomes more likely. If some of the fish they had previously eaten is available this can also be tested to confirm the diagnosis.Preventive efforts include not eating reef fish, not eating high-risk fish such as barracuda, and not eating fish liver, roe, or fish heads.