| Miller–Dieker syndrome | |
|---|---|
| Classification and external resources | |
| ICD-9 | 758.33 |
| OMIM | 247200 |
| DiseasesDB | 29494 |
| MeSH | D054221 |
Miller–Dieker syndrome (MDS), also called Miller–Dieker lissencephaly syndrome (MDLS) and chromosome 17p13.3 deletion syndrome, is an autosomal dominant[1] congenital disorder characterized by a developmental defect of the brain, caused by incomplete neuronal migration.
This syndrome should not be confused with Miller syndrome - an unrelated rare genetic disorder - or Miller Fisher syndrome - a form of Guillain-Barré syndrome.
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The brain is smooth (also known as lissencephaly), has an absence of sulci and gyri, has a cerebral cortex 4 layers thick instead of 6 and shows microcephaly. There is a characteristic facial appearance, delayed growth and mental development, and multiple abnormalities of the brain, heart, kidney and gastrointestinal tract.
Failure to thrive, feeding difficulties, seizures and decreased spontaneous activity are often seen, and death tends to occur in infancy and childhood.
Originally thought to be an autosomal recessive disorder, MDS is now known to be an autosomal dominant disorder, and a haploinsufficiency of one or more genes on chromosome 17p13.[1] Autosomal dominant inheritance means that the defective gene responsible for a disorder is located on an autosome (chromosome 17 is an autosome), and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.
The disorder arises from the deletion of part of 17p (which includes both the LIS1 and 14-3-3 epsilon gene), leading to partial monosomy. There may be unbalanced translocations (ie 17q:17p or 12q:17p), or the presence of a ring chromosome 17.
Although an autosomal dominant disorder,[1] Miller-Dieker syndrome is not easily inherited due to the fact that those afflicted do not always live beyond childhood.[2] They therefore could not pass the gene to the next generation.
The disease may be diagnosed by cytogenetic techniques, testing for a microdeletion at LIS1.[3]
It is named for James Q. Miller[4] and H. Dieker.[5]