Department of Internal Medicine, Jeonbuk National University School of Medicine, Jeonju 54907, Korea.
Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University School of Medicine, Jeonju 54907, Korea.
Medicina (Kaunas). 2022 Nov 3;58(11):1592. doi: 10.3390/medicina58111592.
Schwannomatosis is characterized by the presence of multiple schwannomas without landmarks of NF2. It is considered the rarest form of neurofibromatosis (NF). Here, we report the first case of familial schwannomatosis with regard to the segmental/generalized phenotype, in which the proband and the daughter present a distinct phenotype in this classification. The proband presents a generalized, painless, extradural type of schwannomatosis, while the daughter shows a segmental, painful, intradural type of schwannomatosis. Whole-exome sequencing of the affected individuals revealed a shared novel SMARCB1 gene mutation (c.92A > G, p.Glu31Gly) despite the clinical variability. We thus suggest two points in the diagnosis of familial schwannomatosis: The identified novel germline SMARCB1 variant can be reflective of a phenotypical progression from a segmental to a generalized type of schwannomatosis, or an intrafamilial variability in inherited schwannomatosis, which was not reported in previous literature. The specific combination of somatic NF2 mutations may be a major factor in regulating the severity and scope of the resulting phenotype in schwannomatosis.
神经鞘瘤病的特征是存在多个神经鞘瘤，而没有 NF2 的标志。它被认为是神经纤维瘤病（NF）中最罕见的形式。在这里，我们报告了首例关于节段/全身性表型的家族性神经鞘瘤病病例，其中先证者和女儿在该分类中表现出明显不同的表型。先证者表现为全身性、无痛性、硬膜外型神经鞘瘤病，而女儿则表现为节段性、疼痛性、硬膜内型神经鞘瘤病。受影响个体的外显子组测序显示，尽管临床表现存在差异，但存在共享的新型 SMARCB1 基因突变（c.92A > G，p.Glu31Gly）。因此，我们建议在诊断家族性神经鞘瘤病时注意两点：已确定的新型种系 SMARCB1 变体可能反映了从节段性到全身性神经鞘瘤病表型的进展，或者是遗传神经鞘瘤病中的家族内变异性，这在以前的文献中没有报道过。体细胞 NF2 突变的特定组合可能是调节神经鞘瘤病中表型严重程度和范围的主要因素。
