Medicine:CHAMP1-associated intellectual disability syndrome
| CHAMP1-associated intellectual disability syndrome | |
|---|---|
| Other names | Autosomal dominant intellectual disability 40 |
| Specialty | Medical genetics, pediatrics |
| Symptoms | Developmental delays, intellectual disability, and other multi-systemic symptoms |
| Usual onset | Birth |
| Duration | Lifelong |
| Causes | Genetic mutation in CHAMP1 |
| Prevention | None |
| Prognosis | With treatment, medium to good; without treatment, medium to poor |
| Frequency | Rare; only 36 cases have been described |
| Deaths | - |
CHAMP1-associated intellectual disability syndrome, also known as autosomal dominant intellectual disability type 40, is a rare genetic disorder characterized by intellectual disabilities, developmental delays, facial dysmorphisms, and other anomalies.[1]
Signs and symptoms
Individuals with the disorder often show the following signs and symptoms:[2][3]
- Intellectual disabilities
- Speech delays
- Epicanthic fold
- Drooping of the lower lip
- Feeding difficulties
- Hypotonia of the face
- Ataxia
- Hyperopia
- High palate
- Widespread developmental delays
- Gastroesophageal reflux
- Widespread hypotonia
- Decreased sense of pain
- Joint hypermobility
- Long face
- Constantly open mouth
- Prognathism (pointy chin)
- High occurrence of respiratory tract infections
- Short philtrum
- Stereotypy
- Tented upper lip vermilion
- Upslanted palpebral fissures
- Strabismus
- Autism/autistic-like behaviour
Causes
As its name suggests, the condition is caused by mutations in the CHAMP1 gene, in chromosome 13q34. These mutations are most often missense or nonsense mutations.[1] They are usually sporadic, meaning the condition is not inherited from the parents. However, if people with the disorder were to reproduce, they would have a 1 in 2 chance of giving their children a copy of the gene, because the disorder is autosomal dominant, which means that only one copy of a mutated gene (whether inherited or from a spontaneous error in cell division) is needed to pass it on to a child.
Epidemiology
According to OMIM,[4] only 36 cases have been described in medical literature.[5][6][7][8][9]
References
- ↑ 1.0 1.1 Asakura, Yuta; Osaka, Hitoshi; Aoi, Hiromi; Mizuguchi, Takeshi; Matsumoto, Naomichi; Yamagata, Takanori (2021-08-17). "Intellectual disability and microcephaly associated with a novel CHAMP1 mutation" (in en). Human Genome Variation 8 (1): 34. doi:10.1038/s41439-021-00165-7. ISSN 2054-345X. PMID 34404773. PMC 8371100. https://www.researchgate.net/publication/353953610.
- ↑ "Autosomal dominant intellectual disability 40 - About the Disease - Genetic and Rare Diseases Information Center" (in en). https://rarediseases.info.nih.gov/diseases/13539/autosomal-dominant-intellectual-disability-40.
- ↑ "Gene: CHAMP1 -" (in en-US). https://gene.sfari.org/database/human-gene/CHAMP1.
- ↑ "OMIM Entry - # 616579 - NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED LANGUAGE, AND DYSMORPHIC FEATURES; NEDHILD" (in en-us). https://omim.org/entry/616579.
- ↑ Deciphering Developmental Disorders Study (2015-03-12). "Large-scale discovery of novel genetic causes of developmental disorders". Nature 519 (7542): 223–228. doi:10.1038/nature14135. ISSN 1476-4687. PMID 25533962. Bibcode: 2015Natur.519..223T.
- ↑ Hempel, Maja; Cremer, Kirsten; Ockeloen, Charlotte W.; Lichtenbelt, Klaske D.; Herkert, Johanna C.; Denecke, Jonas; Haack, Tobias B.; Zink, Alexander M. et al. (2015-09-03). "De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment". American Journal of Human Genetics 97 (3): 493–500. doi:10.1016/j.ajhg.2015.08.003. ISSN 1537-6605. PMID 26340335.
- ↑ Isidor, Bertrand; Küry, Sébastien; Rosenfeld, Jill A.; Besnard, Thomas; Schmitt, Sébastien; Joss, Shelagh; Davies, Sally J.; Lebel, Robert Roger et al. (April 2016). "De Novo Truncating Mutations in the Kinetochore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability". Human Mutation 37 (4): 354–358. doi:10.1002/humu.22952. ISSN 1098-1004. PMID 26751395.
- ↑ Garrity, Madison; Kavus, Haluk; Rojas-Vasquez, Marta; Valenzuela, Irene; Larson, Austin; Reed, Sara; Bellus, Gary; Mignot, Cyril et al. (August 2021). "Neurodevelopmental phenotypes in individuals with pathogenic variants in CHAMP1". Cold Spring Harbor Molecular Case Studies 7 (4): a006092. doi:10.1101/mcs.a006092. ISSN 2373-2873. PMID 34021018.
- ↑ Levy, Tess; Lerman, Bonnie; Halpern, Danielle; Frank, Yitzchak; Layton, Christina; Zweifach, Jessica; Siper, Paige M.; Buxbaum, Joseph D. et al. (2022-03-11). "CHAMP1 disorder is associated with a complex neurobehavioral phenotype including autism, ADHD, repetitive behaviors and sensory symptoms". Human Molecular Genetics 31 (15): 2582–2594. doi:10.1093/hmg/ddac018. ISSN 1460-2083. PMID 35271727.
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