LZTR1- and SMARCB1-Related Schwannomatosis

Review
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].

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 identification of a heterozygous germline pathogenic variant in LZTR1 or SMARCB1.

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.

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  • Review