CHAMP1-associated intellectual disability syndrome

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CHAMP1-related neurodevelopmental disorder
Other namesAutosomal Dominant Intellectual Disability type 40 (MRD40), Neurodevelopmental Disorder with Hypotonia, Impaired Language, and Dysmorphic Features (NEDHILD)
Specialty Medical genetics, pediatrics
Symptoms Developmental delay, intellectual disability, severe speech impairment, hypotonia, feeding difficulties
Usual onsetBirth
DurationLifelong
Causes Genetic mutation or deletion in the CHAMP1 gene
Diagnostic method Genetic testing (e.g., WES, WGS, CMA)
TreatmentSupportive care including physiotherapy, occupational therapy, speech therapy, and management of symptoms
Prognosis Varies based on severity; most individuals require lifelong support [1]
FrequencyUltra Rare; less than 250 cases worldwide (as of 2025) [2]

CHAMP1-related neurodevelopmental disorder is an ultra-rare genetic disorder caused by changes to the CHAMP1 gene. [3] The condition is primarily characterized by developmental delay, varying degrees of intellectual disability, and significant speech and language impairment. [4] Other common features include low muscle tone (hypotonia), feeding difficulties, atypical behaviours, and distinctive facial features. [5]

Contents

Signs and symptoms

Individuals with a CHAMP1-related disorder can have a wide range of clinical features, and not every person will have all possible symptoms.

Developmental and Behavioural

Physical and Medical

Causes

The disorder is caused by pathogenic variants (mutations) or deletions of the CHAMP1 gene, which is located on the long (q) arm of chromosome 13 at position 34. [3] The condition is autosomal dominant, meaning a change in only one of the two copies of the gene is sufficient to cause the disorder. In almost all known cases, the genetic change is de novo , meaning it occurred spontaneously and was not inherited from a parent. [4]

Protein Function

The CHAMP1 gene provides instructions for making the CHAMP1 protein, which has several critical roles in the body's cells.

Types of Genetic Variants

Different types of genetic changes can affect the CHAMP1 protein in different ways, which may contribute to the variability in symptoms.

Diagnosis

Diagnosis is confirmed through genetic testing. Whole exome sequencing (WES) or whole genome sequencing (WGS) are used to identify variants within the gene sequence, while a chromosome microarray analysis (CMA) is often used to detect deletions of the entire gene. [3]

Management

There is no cure for CHAMP1-related disorder, but supportive therapies can help manage symptoms and improve quality of life. Management typically involves a multidisciplinary team and may include: [1]

Epidemiology

CHAMP1-related disorder is considered ultra-rare. As of 2025, fewer than 250 individuals have been identified worldwide. [2] The condition was first described in 2015, and it is believed to be underdiagnosed due to limited awareness and access to comprehensive genetic testing. [3] [15]

Research

Active research is focused on better understanding the function of the CHAMP1 gene and the mechanisms of the disorder. Patient organizations, such as the CHAMP1 Research Foundation, play a key role in accelerating this work by funding studies and maintaining patient registries. Future therapeutic strategies under investigation include drug repositioning and genetic therapies, such as antisense oligonucleotides (ASOs), although these are still in the early stages of research.

Support for those affected

There are two main non-profit organizations offering support for those affected by CHAMP1-related disorders:

References

  1. 1 2 3 4 5 Abi Raad S, Salignat V, Auvin S (July 2023). "CHAMP1-Related Disorder: Sharing 20 Years of thorough Clinical Follow-Up and Review of the Literature". Genes (Basel). 14 (8): 1546. doi: 10.3390/genes14081546 . PMC   10454041 . PMID   37628598.
  2. 1 2 "CHAMP1 Patient Registries". CHAMP1 Research Foundation & CHAMP1 UK. As of 2025, less than 250 individuals with a CHAMP1-related NDD have been identified worldwide through patient registries and medical literature.
  3. 1 2 3 4 Hempel M, Cremer K, Ockeloen CW (September 2015). "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. PMC   4564986 . PMID   26340335.
  4. 1 2 Héron D, Tabet AC, Mignot C (October 2018). "De Novo Truncating Mutations in the Kinetore-Microtubules Attachment Gene CHAMP1 Cause Syndromic Intellectual Disability". The American Journal of Human Genetics. 103 (4): 603–611. doi:10.1016/j.ajhg.2018.08.011. PMC   6174321 . PMID   30196985.
  5. 1 2 Tanaka AJ, et al. (May 2016). "De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features". Cold Spring Harbor Molecular Case Studies. 2 (3): a000918. doi:10.1101/mcs.a000661. PMC   4849931 . PMID   27148580.
  6. 1 2 Levy T, et al. (March 2022). "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. PMC   9396938 . PMID   35271727.
  7. 1 2 3 4 Schaaf CP, Koster J, Foulds N, et al. (May 2023). "A disease conceptual model for CHAMP1-related disorder". Journal of Neurodevelopmental Disorders. 15 (1): 19. doi: 10.1186/s12941-023-00586-y . PMC   10202970 . PMID   37202758.
  8. 1 2 3 "CHAMP1 Gene Guide". Simons Searchlight. 25 October 2024. Retrieved 10 September 2025.
  9. Itoh G, et al. (January 2011). "CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment". The EMBO Journal. 30 (1): 130–44. doi:10.1038/emboj.2010.286. PMC   3018590 . PMID   21081896.
  10. Nagai K, et al. (September 2022). "Deficiency of CHAMP1, a gene related to intellectual disability, causes impaired neuronal development and a mild behavioural phenotype". Brain Communications. 4 (5) fcac220. doi:10.1093/braincomms/fcac220. PMC   9463567 . PMID   36106092.
  11. Li F, et al. (February 2025). "CHAMP1 complex directs heterochromatin assembly and promotes homology-directed DNA repair". Nat Commun. 16 (1) 1714. Bibcode:2025NatCo..16.1714L. doi:10.1038/s41467-025-56834-6. PMC   11832927 . PMID   39962076.
  12. Levy T, et al. (September 2023). "Prospective phenotyping of CHAMP1 disorder indicates that coding mutations may not act through haploinsufficiency". Human Genetics. 142 (9): 1385–1394. doi:10.1007/s00439-023-02578-6. PMC   10449971 . PMID   37454340.
  13. Yoshizaki Y, et al. (December 2024). "CHAMP1 premature termination codon mutations found in individuals with intellectual disability cause a homologous recombination defect through haploinsufficiency". Scientific Reports. 14 (1) 31904. Bibcode:2024NatSR..1431904Y. doi:10.1038/s41598-024-83435-y. PMC   11686235 . PMID   39738383.
  14. Ben-Haim R, et al. (October 2020). "CHAMP1 mutations cause refractory infantile myoclonic epilepsy". J Pediatr Neurol. 18: 27–32. doi:10.1055/s-0039-1693158.
  15. Deciphering Developmental Disorders Study (March 2015). "Large-scale discovery of novel genetic causes of developmental disorders". Nature. 519 (7542): 223–8. Bibcode:2015Natur.519..223T. doi:10.1038/nature14135. PMC   5955210 . PMID   25533962.