From the Department of Neurology (K.M., N.C.V., B.G.M.v.E., C.G.C.H.), Radboud University Medical Center, Nijmegen; Departments of Human Genetics (R.J.L.F.L., P.J.v.d.V., M.L.v.d.B., S.M.v.d.M.), Clinical Genetics (M.K.), and Neurology (U.A.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Pediatrics (J.M.G.), Cedars Sinai Medical Center, Los Angeles, CA; Department of Medical Genetics (A.E.L.), MassGeneral Hospital for Children, Boston, MA; Center for Genomic Medicine and Department of Neurology (H.B.), Massachusetts General Hospital, Boston; Department of Pathology (S.A.M.), University of Iowa Hospitals and Clinics, Iowa City; The John Walton Muscular Dystrophy Research Centre (K.J., T.E., A.T., V.S.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Neuromuscular Consult Unit (S.K.G.), Bilbo-Basurtu Erakunde Sanitario Integratua, Organización Sanitaria Integrada Bilbao-Basurto, Spain; Centre de Référence des Maladies Neuromusculaires (S.S.), Nice, France; Department of Neurology (R.T.), University of Rochester Medical Center, NY; Division of Human Biology (S.J.T.), Fred Hutchinson Cancer Research Center, Seattle, WA; and National Institute of Environmental Health Sciences (N.D.S.), Research Triangle Park, NC.
Neurology. 2018 Aug 7;91(6):e562-e570. doi: 10.1212/WNL.0000000000005958. Epub 2018 Jul 6.
To determine whether congenital arhinia/Bosma arhinia microphthalmia syndrome (BAMS) and facioscapulohumeral muscular dystrophy type 2 (FSHD2), 2 seemingly unrelated disorders both caused by heterozygous pathogenic missense variants in the gene, might represent different ends of a broad single phenotypic spectrum associated with SMCHD1 dysfunction.
We examined and/or interviewed 14 patients with FSHD2 and 4 unaffected family members with N-terminal pathogenic missense variants to identify BAMS subphenotypes.
None of the patients with FSHD2 or family members demonstrated any congenital defects or dysmorphic features commonly found in patients with BAMS. One patient became anosmic after nasal surgery and one patient was hyposmic; one man was infertile (unknown cause) but reported normal pubertal development.
These data suggest that arhinia/BAMS and FSHD2 do not represent one phenotypic spectrum and that pathogenic variants by themselves are insufficient to cause either of the 2 disorders. More likely, both arhinia/BAMS and FSHD2 are caused by complex oligogenic or multifactorial mechanisms that only partially overlap at the level of
确定先天性无鼻/博斯马无鼻小眼球综合征（BAMS）和面肩肱型肌营养不良 2 型（FSHD2）是否代表与 SMCHD1 功能障碍相关的广泛单一表型谱的不同末端，这两种疾病均由基因中的杂合致病性错义变异引起。
我们检查和/或访谈了 14 名 FSHD2 患者和 4 名携带 N 端致病性错义变异的无相关家族成员，以确定 BAMS 亚型。
FSHD2 患者或家族成员均未表现出 BAMS 患者常见的任何先天性缺陷或畸形特征。一名患者在鼻手术后失去嗅觉，一名患者嗅觉减退；一名男性不育（原因不明），但报告青春期发育正常。
这些数据表明，无鼻/博斯马无鼻小眼球综合征和 FSHD2 不代表单一表型谱，致病性变异本身不足以引起这两种疾病中的任何一种。更有可能的是，无鼻/博斯马无鼻小眼球综合征和 FSHD2 均由复杂的寡基因或多因素机制引起，这些机制在
