Familial dysautonomia
| Familial dysautonomia | |
|---|---|
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| Facial features of a patient with familial dysautonomia over time. Note flattening of upper lip. By age 10 years prominence of lower jaw is apparent and by age 19 years there is mild erosion of right nostril due to inadvertent self-mutilation. | |
| Classification and external resources | |
| Specialty | neurology |
| ICD-10 | G90.1 |
| ICD-9-CM | 742.8 |
| OMIM | 223900 |
| DiseasesDB | 11631 |
| MedlinePlus | 001387 |
| eMedicine | oph/678 |
| MeSH | D004402 |
| GeneReviews | |
Familial dysautonomia (FD), sometimes called Riley–Day syndrome and hereditary sensory and autonomic neuropathy type III (HSAN-III), is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms, including insensitivity to pain, inability to produce tears, poor growth, and labile blood pressure (episodic hypertension and postural hypotension). People with FD have frequent vomiting crises, pneumonia, problems with speech and movement, difficulty swallowing, inappropriate perception of heat, pain, and taste, as well as unstable blood pressure and gastrointestinal dysmotility. FD does not affect intelligence. Originally reported by Conrad Milton Riley and Richard Lawrence Day in 1949, FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies (HSAN). All HSAN are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.
The most distinctive clinical feature is the absence of overflow tears with emotional crying after age 7 months. This symptom can manifest less dramatically as persistent bilateral eye irritation. There is also a high prevalence of breech presentation. Other symptoms include weak or absent suck and poor tone, poor suck and misdirected swallowing, and red blotching of skin.
Symptoms in an older child with familial dysautonomia might include:
Familial dysautonomia is the result of mutations in IKBKAP gene on chromosome 9, which encodes for the IKAP protein (IkB kinase complex-associated protein). There have been three mutations in IKBKAP identified in individuals with FD. The most common FD-causing mutation occurs in intron 20 of the donor gene. Conversion of T→C in intron 20 of the donor gene resulted in shift splicing that generates an IKAP transcript lacking exon 20. Translation of this mRNA results in a truncated protein lacking all of the amino acids encoded by exons 20-37. Another less common mutation is a G→C conversion resulting in one amino acid mutation in 696, where Proline substitutes normal Arginine. The decreased amount of functional IKAP protein in cells causes familial dysautonomia.
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