A heritable form of SMARCE1-related meningiomas with important implications for follow-up and family screening

Abstract

Childhood meningiomas are rare. Recently, a new hereditary tumor predisposition syndrome has been discovered, resulting in an increased risk for spinal and intracranial clear cell meningiomas (CCMs) in young patients. Heterozygous loss-of-function germline mutations in the SMARCE1 gene are causative, giving rise to an autosomal dominant inheritance pattern. We report on an extended family with a pediatric CCM patient and an adult CCM patient and several asymptomatic relatives carrying a germline SMARCE1 mutation, and discuss difficulties in genetic counseling for this heritable condition. Because of the few reported cases so far, the lifetime risk of developing meningiomas for SMARCE1 mutation carriers is unclear and the complete tumor spectrum is unknown. There is no surveillance guideline for asymptomatic carriers nor a long-term follow-up recommendation for SMARCE1-related CCM patients as yet. Until more information is available about the penetrance and tumor spectrum of the condition, we propose the following screening advice for asymptomatic SMARCE1 mutation carriers: neurological examination and MRI of the brain and spine, yearly from diagnosis until the age of 18 and once every 3 years thereafter, or in between if there are clinical symptoms. This advice can also be used for long-term patient follow-up. More data is needed to optimize this proposed screening advice.

The developmental and pathogenic roles of BAF57, a special subunit of the BAF chromatin‐remodeling complex

“…Mutations in BAF57 as a cause of spinal clear cell meningiomas were reported in 2013 . Subsequently, 18 different mutations have been identified in more than 20 patients with familial meningiomas . At least 10 of these mutations were confirmed in the germline .…”

“…Subsequently, 18 different mutations have been identified in more than 20 patients with familial meningiomas . At least 10 of these mutations were confirmed in the germline . Although the first BAF57 mutations were associated with the spinal region, further work identified these mutations in intracranial meningiomas.…”

SMARCE1 mutation screening in classification of clear cell meningiomas

“…In case of CCM, germline loss‐of‐function mutations in the SMARCE1 chromatin remodelling factor were identified as a cause of both spinal and cranial CCM . To date, 12 families with SMARCE1 ‐associated CCM have been reported (Table ) . SMARCE1 mutations appear to be specific for the clear cell histological subtype, rather than tumour location or syndromic presentation .…”

Recent Advances in Meningioma Immunogenetics

“…Mutations in the Hedgehog family member SUFU are also found at low frequencies in sporadic meningiomas, though germline mutations are also present in familial meningioma (33). Additional hedgehog family germline mutations occur in SMARCE1 and SMARCB1, though these carry less risk of recurrence than familial NF2 mutations (34)(35)(36).…”