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

SYNE1 Deficiency

Marie Beaudin  1 , Pierre-Luc Gamache  1 , François Gros-Louis  2 , Nicolas Dupré  1
Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Anne Amemiya
, editors.
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].
Affiliations
Free Books & Documents
Review

SYNE1 Deficiency

Marie Beaudin et al.
Free Books & Documents

Excerpt

Clinical characteristics: SYNE1 deficiency comprises a phenotypic spectrum that ranges from autosomal recessive cerebellar ataxia at the mild end to arthrogryposis multiplex congenita (AMC) at the severe end. SYNE1-deficient cerebellar ataxia, the most commonly recognized manifestation of SYNE1 deficiency to date, is a slowly progressive disorder typically beginning in adulthood (age range 6-45 years). While some individuals have a pure cerebellar syndrome (i.e., cerebellar ataxia, dysarthria, dysmetria, abnormalities in ocular saccades and smooth pursuit), many also have upper motor neuron dysfunction (spasticity, hyperreflexia, Babinski sign) and/or lower motor neuron dysfunction (amyotrophy, reduced reflexes, fasciculations). Most individuals develop features of the cerebellar cognitive and affective syndrome (i.e., significant deficits in attention, executive functioning, verbal working memory, and visuospatial/visuoconstructional skills). The two less common phenotypes are SYNE1-deficient childhood-onset multisystem disease (ataxia, upper and lower motor neuron dysfunction, muscle weakness and wasting, intellectual disability) and SYNE1-deficient arthrogryposis multiplex congenita (decreased fetal movements and severe neonatal hypotonia associated with multiple congenital joint contractures including clubfoot).

Diagnosis/testing: The diagnosis of SYNE1 deficiency is established in a proband with suggestive findings and biallelic SYNE1 pathogenic variants identified by molecular genetic testing.

Management: Treatment of manifestations: There is no specific treatment for SYNE1 deficiency. The goals of treatment are to maximize function and reduce complications. Each affected individual should be managed by a multidisciplinary team of relevant specialists including neurologists, occupational therapists, physical therapists, physiatrists, orthopedists, nutritionists, speech therapists, respiratory therapists, and psychologists depending on the clinical manifestations.

Surveillance: Annual (or more often as needed) neurologic examination; assessment of mobility and self-help skills (as they relate to ataxia, spasticity, weakness), dysarthria, dysphagia, cognition, and psychiatric manifestations.

Genetic counseling: SYNE1 deficiency is inherited in an autosomal recessive manner. The parents of an affected individual are obligate heterozygotes (i.e., carriers of one SYNE1 pathogenic variant). At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SYNE1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal diagnosis for a pregnancy at increased risk, and preimplantation genetic testing are possible.

PubMed Disclaimer

Similar articles

  • Ataxia-Telangiectasia.
    Veenhuis S, van Os N, Weemaes C, Kamsteeg EJ, Willemsen M. Veenhuis S, et al. 1999 Mar 19 [updated 2023 Oct 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 1999 Mar 19 [updated 2023 Oct 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301790 Free Books & Documents. Review.
  • Adenosine Deaminase Deficiency.
    Hershfield M, Tarrant T. Hershfield M, et al. 2006 Oct 3 [updated 2024 Mar 7]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2006 Oct 3 [updated 2024 Mar 7]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301656 Free Books & Documents. Review.
  • Friedreich Ataxia.
    Bidichandani SI, Delatycki MB, Napierala M, Duquette A. Bidichandani SI, et al. 1998 Dec 18 [updated 2024 Oct 31]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 1998 Dec 18 [updated 2024 Oct 31]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301458 Free Books & Documents. Review.
  • ATP1A3-Related Disorder.
    Brashear A, Sweadner KJ, Haq I, Napoli E, Ozelius L. Brashear A, et al. 2008 Feb 7 [updated 2024 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2008 Feb 7 [updated 2024 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301294 Free Books & Documents. Review.
  • Citrullinemia Type I.
    Quinonez SC, Lee KN. Quinonez SC, et al. 2004 Jul 7 [updated 2022 Aug 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2004 Jul 7 [updated 2022 Aug 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301631 Free Books & Documents. Review.
See all similar articles

References

    1. Algahtani H, Marzouk Y, Algahtani R, Salman S, Shirah B. Autosomal recessive cerebellar ataxia type 1 mimicking multiple sclerosis: a report of two siblings with a novel mutation in SYNE1 gene in a Saudi family. J Neurol Sci. 2017;372:97–100. - PubMed
    1. Attali R, Warwar N, Israel A, Gurt I, McNally E, Puckelwartz M, Glick B, Nevo Y, Ben-Neriah Z, Melki J. Mutation of SYNE-1, encoding an essential component of the nuclear lamina, is responsible for autosomal recessive arthrogryposis. Hum Mol Genet. 2009;18:3462–9. - PubMed
    1. Baumann M, Steichen-Gersdorf E, Krabichler B, Petersen BS, Weber U, Schmidt WM, Zschocke J, Müller T, Bittner RE, Janecke AR. Homozygous SYNE1 mutation causes congenital onset of muscular weakness with distal arthrogryposis: a genotype-phenotype correlation. Eur J Hum Genet. 2017;25:262–6. - PMC - PubMed
    1. Bürk K, Sival DA. Scales for the clinical evaluation of cerebellar disorders. Handb Clin Neurol. 2018;154:329–39. - PubMed
    1. Chen Z, Ren Z, Mei W, Ma Q, Shi Y, Zhang Y, Li S, Xiang L, Zhang J. A novel SYNE1 gene mutation in a Chinese family of Emery-Dreifuss muscular dystrophy-like. BMC Med Genet. 2017;18:63. - PMC - PubMed

LinkOut - more resources