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22q13 deletion syndrome
The deletion of the tip of the chromosome 22 is related to autism, moderate to severe developmental delay, and mental retardation. It is known as 22q13 deletion syndrome or Phelan-McDermid syndrome.
Additional recommended knowledge
The deletion affects the terminal region of the long arm of chromosome 22 (the paternal chromosome in 75% of cases), from 22q13.3 to 22qter. Although the deletion is most typically a result of a de novo mutation, there is an inherited form resulting from familial chromosomal translocations involving the 22 chromosome. In the de novo form, the size of the deletion is variable and can go from 130kbp (130,000 base pairs) to 9Mbp (9,000,000 base pairs). While some clinical signs correlate with the size of the deletion, the main traits of the syndrome appear to be independent of the deletion size, and only related to the presence of the Shank3 gene . The haploinsufficiency of Shank3 is thought to be the responsible for the neurological deficits of the syndrome (Wilson et al., 2003).
The proteins encoded by the Shank genes assemble glutamate receptors with their intracellular signaling apparatus and cytoskeleton at the postsynaptic density. They are important for the formation and stabilisation of synapses:
In 2006, a group lead by Thomas Bourgeron from the Pasteur Institute in France, found anomalies of the 22q13 locus in five children with diagnosis of autism and Asperger syndrome. While the absence of the Shank3 gene was found in children with the typical characteristics of the Phelan-McDermid syndrome, its duplication was found in one child diagnosed with Asperger syndrome, a type of high-functioning autism.
Van Bokhoven et al. (1997) have also assigned the WNT7B gene to 22q13 . Wnt7b acts through Dvl1 to the regulation of dendritic development. Rosso et al. (2005) found that its overexpression resulted in increased dendritic branching in cultured mouse hippocampal neurons. Knockout mice for Dvl1 are viable, fertile and structurally normal, but show reduced social interaction and abnormal sleeping patterns (Lijam et al, 1997)
The incidence of the 22q13 deletion syndrome is uncertain. The advanced genetic technique essential for diagnosis, fluorescent in situ hybridization (FISH), has only been available since 1998, and currently requires specialized laboratory facilities. Current thinking is that 22q13 deletion syndrome remains largely under-diagnosed, and may be one of the principal causes of idiopathic mental retardation (Manning and al. 2004).
Almost all children affected by the 22q13 deletion have absent or severely delayed speech. They exhibit only minor facial dysmorphism; thin, flaky toenails (78%); large, fleshy hands (68%); large feet; prominent, poorly formed ears (65%); and other characteristics which are not visually apparent: hypotonia (97%); normal to accelerated growth (95%); increased tolerance to pain (86%); seizures (unknown percentage); strabismus; anomalies of the spine; poor central vision.
Categories: Genetic disorders | Pediatrics | Syndromes
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "22q13_deletion_syndrome". A list of authors is available in Wikipedia.|