Screening of potential novel candidate genes in schwannomatosis patients.

Schwannomatosis comprises a group of hereditary tumor predisposition syndromes characterized by, usually benign, multiple nerve sheath tumors, which frequently cause severe pain that does not typically respond to drug treatments. The most common schwannomatosis-associated gene is NF2, but SMARCB1 and LZTR1 are also associated. There are still many cases in which no pathogenic variants (PVs) have been identified, suggesting the existence of as yet unidentified genetic risk factors.

Prenatal Detection of PIK3CA-related Overgrowth Spectrum in Cultured Amniocytes Using Long-range PCR and Next-generation Sequencing.

Mutations in PIK3CA are associated with overgrowth spectrum disorders including excessive growth in some areas of the body and the central nervous system. Alterations in PIK3CA occur as somatic, postzygotic events and confer a mosaic genotype with variability in phenotypic expression being commonly observed. We describe the second reported prenatal diagnosis of a PIK3CA-related overgrowth spectrum disorder.

Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis.

Objective: To determine the specificity of the current clinical diagnostic criteria for neurofibromatosis type 2 (NF2) relative to the requirement for unilateral vestibular schwannoma (VS) and at least 2 other NF2-related tumors.

Methods: We interrogated our Manchester NF2 database, which contained 205 individuals meeting NF2 criteria who initially presented with a unilateral VS. Of these, 83 (40.

The Contribution of Whole Gene Deletions and Large Rearrangements to the Mutation Spectrum in Inherited Tumor Predisposing Syndromes.

Heterozygous whole gene deletions (WGDs), and intragenic microdeletions, account for a significant proportion of mutations underlying cancer predisposition syndromes. We analyzed the frequency and genotype-phenotype correlations of microdeletions in 12 genes (BRCA1, BRCA2, TP53, MSH2, MLH1, MSH6, PMS2, NF1, NF2, APC, PTCH1, and VHL) representing seven tumor predisposition syndromes in 5,897 individuals (2,611 families) from our center. Overall, microdeletions accounted for 14% of identified mutations.

What are the implications in individuals with unilateral vestibular schwannoma and other neurogenic tumors?

Objectives: Individuals who develop a unilateral vestibular schwannoma (VS) and other neurogenic tumors are at high risk of having the inherited condition neurofibromatosis Type 2 (NF2). The risk of bilateral disease and transmission risk to offspring are important in surgical planning and counseling. The authors have attempted to resolve these risks.