Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review

CHCHD10-Related Disorders

Samira Ait-El-Mkadem Saadi  1 , Annabelle Chaussenot  1 , Sylvie Bannwarth  1 , Cécile Rouzier  1 , Véronique Paquis-Flucklinger  1
Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen W Gripp, Anne Amemiya
, editors.
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].
Affiliations
Free Books & Documents
Review

CHCHD10-Related Disorders

Samira Ait-El-Mkadem Saadi et al.
Free Books & Documents

Excerpt

Clinical characteristics: CHCHD10-related disorders are characterized by a spectrum of adult-onset neurologic phenotypes that can include:

  1. Mitochondrial myopathy (may also be early onset): weakness, amyotrophy, exercise intolerance

  2. Amyotrophic lateral sclerosis (ALS): progressive degeneration of upper motor neurons and lower motor neurons

  3. Frontotemporal dementia (FTD): slowly progressive behavioral changes, language disturbances, cognitive decline, extrapyramidal signs

  4. Late-onset spinal motor neuronopathy (SMA, Jokela type): weakness, cramps, and/or fasciculations; areflexia

  5. Axonal Charcot-Marie-Tooth neuropathy: slowly progressive lower-leg muscle weakness and atrophy, small hand muscle weakness, loss of tendon reflexes, sensory abnormalities

  6. Cerebellar ataxia: gait ataxia, kinetic ataxia (progressive loss of coordination of lower- and upper-limb movements), dysarthria/dysphagia, nystagmus, cerebellar oculomotor disorder

Because of the recent discovery of CHCHD10-related disorders and the limited number of affected individuals reported to date, the natural history of these disorders (except for SMAJ caused by the p.Gly66Val pathogenic variant) is largely unknown.

Diagnosis/testing: The diagnosis is established when a heterozygous CHCHD10 pathogenic variant is detected in an individual with one or more characteristic clinical findings.

Management: Treatment of manifestations: Adequate nutrition and weight maintenance are essential. Appropriate bracing and stretching can minimize joint contractures, which are often painful and can interfere with caregiving. Those with weakness benefit from assistance with ambulation and posture. Management of ALS, FTD, SMA, and cerebellar ataxia is the same as for other causes of these disorders.

Surveillance: Regular evaluations to detect manifestations that can occur with time including neurologic deficits, psychiatric abnormalities, impaired respiratory function, and sensorineural hearing loss.

Agents/circumstances to avoid: Baclofen (used to treat spasticity) can sometimes worsen muscle weakness; some drugs used to treat the behavioral manifestations of FTD may worsen dysarthria, dysphagia, and/or respiratory weakness.

Genetic counseling: CHCHD10-related disorders are inherited in an autosomal dominant manner. Many individuals diagnosed with a CHCHD10-related disorder have an affected parent. The proportion of probands with a CHCHD10-related disorder caused by a de novo pathogenic variant is unknown. Each child of an individual with a CHCHD10-related disorder has a 50% chance of inheriting the CHCHD10 pathogenic variant. Because significant clinical heterogeneity is observed within families, it is impossible to accurately predict the age at onset and manifestations that will develop in individuals who inherit a CHCHD10 pathogenic variant. Once the CHCHD10 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk for a CHCHD10-related disorder and preimplantation genetic testing are possible.

PubMed Disclaimer

Similar articles

  • ATP1A3-Related Neurologic Disorders.
    Brashear A, Sweadner KJ, Cook JF, Swoboda KJ, Ozelius L. Brashear A, et al. 2008 Feb 7 [updated 2018 Feb 22]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2008 Feb 7 [updated 2018 Feb 22]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301294 Free Books & Documents. Review.
  • Autosomal Dominant TRPV4 Disorders.
    McCray BA, Schindler A, Hoover-Fong JE, Sumner CJ. McCray BA, et al. 2014 May 15 [updated 2020 Sep 17]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2014 May 15 [updated 2020 Sep 17]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 24830047 Free Books & Documents. Review.
  • LMNB1-Related Autosomal Dominant Leukodystrophy.
    Raininko R, Gosky M, Padiath QS. Raininko R, et al. 2016 Jan 7 [updated 2021 Jul 15]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2016 Jan 7 [updated 2021 Jul 15]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 26749591 Free Books & Documents. Review.
  • TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia.
    Manohar V, Crowley L, Sreedharan J. Manohar V, et al. 2009 Apr 23 [updated 2023 Jan 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2009 Apr 23 [updated 2023 Jan 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301761 Free Books & Documents. Review.
  • GARS1-Associated Axonal Neuropathy.
    Markovitz R, Ghosh R, Lotze T, Potocki L. Markovitz R, et al. 2006 Nov 8 [updated 2021 Jul 22]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. 2006 Nov 8 [updated 2021 Jul 22]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 20301420 Free Books & Documents. Review.
See all similar articles

References

    1. Ajroud-Driss S, Fecto F, Ajroud K, Lalani I, Calvo SE, Mootha VK, Deng HX, Siddique N, Tahmoush AJ, Heiman-Patterson TD, Siddique T. Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy. Neurogenetics. 2015;16:1–9. - PMC - PubMed
    1. Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, Van Damme P, Hardiman O, Kollewe K, Morrison KE, Petri S, Pradat PF, Silani V, Tomik B, Wasner M, Weber M, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. Eur J Neurol. 2012;19:360–75. - PubMed
    1. Anderson CJ, Bredvik K, Burstein SR, Davis C, Meadows SM, Dash J, Case L, Milner TA, Kawamata H, Zuberi A, Piersigilli A, Lutz C, Manfredi G. ALS/FTD mutant CHCHD10 mice reveal a tissue-specific toxic gain-of-function and mitochondrial stress response. Acta Neuropathol. 2019;138:103–21. - PMC - PubMed
    1. Auranen M, Ylikallio E, Shcherbii M, Paetau A, Kiuru-Enari S, Toppila JP, Tyynismaa H. CHCHD10 variant p.(Gly66Val) causes axonal Charcot-Marie-Tooth disease. Neurol Genet. 2015;1:e1. - PMC - PubMed
    1. Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K, Berg-Alonso L, Kageyama Y, Serre V, Moore DG, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N'Guyen K, de Septenville A, Brice A, Yu-Wai-Man P, Sesaki H, Pouget J, Paquis-Flucklinger V. A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement. Brain. 2014;137:2329–45. - PMC - PubMed

LinkOut - more resources

-