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

LZTR1- and SMARCB1-Related Schwannomatosis

Radhika Dhamija  1 , Scott Plotkin  2 , Alicia Gomes  3 , Dusica Babovic-Vuksanovic  4
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

LZTR1- and SMARCB1-Related Schwannomatosis

Radhika Dhamija et al.
Free Books & Documents

Excerpt

Clinical characteristics: LZTR1- and SMARCB1-related schwannomatosis are characterized by a predisposition to develop multiple non-intradermal schwannomas. Individuals most commonly present between the second and fourth decade of life. The most common presenting feature is localized or diffuse pain or asymptomatic mass. Schwannomas most often affect peripheral nerves and spinal nerves. Meningiomas have only been reported in individuals with SMARCB1-related schwannomatosis. Malignancy remains a risk especially in individuals with SMARCB1-related schwannomatosis.

Diagnosis/testing: The diagnosis of LZTR1- or SMARCB1-related schwannomatosis is established in a proband with characteristic clinical findings and a heterozygous germline pathogenic variant in LZTR1 or SMARCB1 identified by molecular genetic testing.

Management: Treatment of manifestations: Comprehensive, multimodal approach to pain management, guided by a pain management specialist or neurologist; referral to mental health professionals as needed for anxiety and/or depression; surgery for schwannomas associated with uncontrolled localized pain or a neurologic deficit; meningioma treatment as for sporadic meningioma.

Surveillance: Annual neurologic examination and pain assessment; brain and spine MRI or whole-body MRI every two to three years beginning at age 12 years, with fine cuts through internal auditory canal in those w/LZTR1-related schwannomatosis; assessment for anxiety and depression annually or as needed.

Agents/circumstances to avoid: Radiation can increase the risk for malignant transformation and should be avoided when possible.

Evaluation of relatives at risk: It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from surveillance and clinical management.

Genetic counseling: LZTR1- and SMARCB1-related schwannomatosis are inherited in an autosomal dominant manner with reduced penetrance. Fewer than 20% of individuals diagnosed with LZTR1- or SMARCB1-related schwannomatosis have an affected parent. In families in which the proband represents a simplex case, the proportion of probands with a de novo pathogenic variant is approximately 30% for LZTR1-related schwannomatosis and 10% for SMARCB1-related schwannomatosis. Each child of an individual with LZTR1- or SMARCB1-related schwannomatosis has up to a 50% chance of inheriting a pathogenic variant. Once a germline LZTR1 or SMARCB1 pathogenic variant has been identified in an affected family member, predictive testing for at-risk asymptomatic family members and prenatal and preimplantation genetic testing are possible.

PubMed Disclaimer

Similar articles

  • Rhabdoid Tumor Predisposition Syndrome.
    Nemes K, Bens S, Bourdeaut F, Johann P, Kordes U, Siebert R, Frühwald MC. Nemes K, et al. 2017 Dec 7 [updated 2022 May 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2017 Dec 7 [updated 2022 May 12]. 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: 29215836 Free Books & Documents. Review.
  • NF2-Related Schwannomatosis.
    Evans DG. Evans DG. 1998 Oct 14 [updated 2023 Apr 20]. 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 Oct 14 [updated 2023 Apr 20]. 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: 20301380 Free Books & Documents. Review.
  • Hemophilia B.
    Konkle BA, Nakaya Fletcher S. Konkle BA, et al. 2000 Oct 2 [updated 2024 Jun 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2000 Oct 2 [updated 2024 Jun 6]. 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: 20301668 Free Books & Documents. Review.
  • Phelan-McDermid Syndrome-SHANK3 Related.
    Phelan K, Rogers RC, Boccuto L. Phelan K, et al. 2005 May 11 [updated 2024 Jun 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2005 May 11 [updated 2024 Jun 6]. 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: 20301377 Free Books & Documents. Review.
  • Li-Fraumeni Syndrome.
    Schneider K, Zelley K, Nichols KE, Schwartz Levine A, Garber J. Schneider K, et al. 1999 Jan 19 [updated 2024 Sep 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 Jan 19 [updated 2024 Sep 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: 20301488 Free Books & Documents. Review.
See all similar articles

References

    1. Antinheimo J, Sankila R, Carpen O, Pukkala E, Sainio M, Jaaskelainen J. Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas. Neurology. 2000;54:71-6. - PubMed
    1. Bacci C, Sestini R, Provenzano A, Paganini I, Mancini I, Porfirio B, Vivarelli R, Genuardi M, Papi L. Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1 mutation. Neurogenetics. 2010;11:73-80. - PubMed
    1. Bourdeaut F, Lequin D, Brugières L, Reynaud S, Dufour C, Doz F, André N, Stephan JL, Pérel Y, Oberlin O, Orbach D, Bergeron C, Rialland X, Fréneaux P, Ranchere D, Figarella-Branger D, Audry G, Puget S, Evans DG, Pinas JC, Capra V, Mosseri V, Coupier I, Gauthier-Villars M, Pierron G, Delattre O. Frequent hSNF5/INI1 germline mutations in patients with rhabdoid tumor. Clin Cancer Res. 2011;17:31-8. - PubMed
    1. Christiaans I, Kenter SB, Brink HC, van Os TA, Baas F, van den Munckhof P, Kidd AM, Hulsebos TJ. Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas. J Med Genet. 2011;48:93-7. - PubMed
    1. Conboy E, Dhamija R, Wang M, Xie J, Dyck PJ, Bridges AG, Spinner RJ, Clayton AC, Watson RE, Messiaen L, Babovic-Vuksanovic D. Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. J Med Genet. 2016;53:123-6. - PubMed

LinkOut - more resources