Division of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.
Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA.
Am J Med Genet A. 2020 Aug;182(8):1923-1932. doi: 10.1002/ajmg.a.61637. Epub 2020 Jun 7.
Baraitser-Winter cerebrofrontofacial syndrome (BWCS) is a rare, autosomal dominant condition that is characterized by intellectual disability, distinctive craniofacial features, structural brain abnormalities, seizures, microcephaly, hearing loss, and ocular colobomas. The first three cases were described in 1988 by Baraitser and Winter and included two siblings and an unrelated third patient. Subsequently, causative missense variants in the ACTB and ACTG1 genes were identified, with de novo occurrence in patients with the condition. Herein, we describe two adult siblings who were born to unaffected parents and who were diagnosed with BWCS in their fourth and sixth decade of life following exome sequencing performed for intellectual disability. We review the literature reports of adult patients with BWCS to document the clinical features and phenotypic variability that can occur later in life. This is the first molecularly confirmed report of germline mosaicism in BWCS and one of only a few reports to describe two BWCS patients belonging to the same family.
Baraitser-Winter 脑面综合征（BWCS）是一种罕见的常染色体显性遗传疾病，其特征为智力障碍、独特的颅面特征、结构性脑异常、癫痫发作、小头畸形、听力损失和眼部虹膜缺损。1988 年，Baraitser 和 Winter 首次描述了前三个病例，包括两个兄弟姐妹和一个无血缘关系的第三位患者。随后，在该疾病患者中发现了 ACTB 和 ACTG1 基因的致病变异体，其为新生突变。在此，我们描述了两名成年同胞，他们出生于未受影响的父母，在因智力障碍进行外显子组测序后，在第四和第六个十年被诊断为 BWCS。我们回顾了 BWCS 成年患者的文献报告，以记录生命后期可能出现的临床特征和表型变异性。这是首次在 BWCS 中分子证实的种系嵌合体报告，也是少数描述属于同一家庭的两名 BWCS 患者的报告之一。
