Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
Division of Dermatology, Department of Clinical and Experimental Sciences, Spedali Civili University Hospital, Brescia, Italy.
Orphanet J Rare Dis. 2017 Sep 7;12(1):153. doi: 10.1186/s13023-017-0704-3.
Spondylodysplastic EDS (spEDS) is a rare connective tissue disorder that groups the phenotypes caused by biallelic B4GALT7, B3GALT6, and SLC39A13 mutations. In the 2017 EDS nosology, minimal criteria (general and gene-specific) for a clinical suspicion of spEDS have been proposed, but molecular analysis is required to reach a definite diagnosis. The majority of spEDS patients presented with short stature, skin hyperextensibility, facial dysmorphisms, peculiar radiological findings, muscle hypotonia and joint laxity and/or its complications. To date only 7 patients with β4GALT7-deficiency (spEDS-B4GALT7) have been described and their clinical data suggested that, in addition to short stature and muscle hypotonia, radioulnar synostosis, hypermetropia, and delayed cognitive development might be a hallmark of this specific type of spEDS. Additional 22 patients affected with an overlapping phenotype, i.e., Larsen of Reunion Island syndrome, all carrying a homozygous B4GALT7 mutation, are also recognized.
Herein, we report on a 30-year-old Moroccan woman who fitted the minimal criteria to suspect spEDS, but lacked radioulnar synostosis and intellectual disability and presented with neurosensorial hearing loss and limb edema of lymphatic origin. Sanger sequencing of B4GALT7 was performed since the evaluation of the spEDS gene-specific minor criteria suggested this specific subtype. Mutational screening revealed the homozygous c.829G>T, p.Glu277* pathogenetic variant leading to aberrant splicing.
Our findings expand both the clinical and mutational spectrum of this ultrarare connective tissue disorder. The comparison of the patient's features with those of the other spEDS and Larsen of Reunion Island syndrome patients reported up to now offers future perspectives for spEDS nosology and clinical research in this field.
Spondylodysplastic EDS（spEDS）是一种罕见的结缔组织疾病，它将由双等位基因 B4GALT7、B3GALT6 和 SLC39A13 突变引起的表型分组。在 2017 年的 EDS 分类学中，提出了 spEDS 临床疑似的最低标准（一般和基因特异性），但需要进行分子分析才能做出明确的诊断。大多数 spEDS 患者表现为身材矮小、皮肤过度伸展性、面部畸形、特殊的影像学发现、肌肉张力减退和/或关节松弛及其并发症。迄今为止，仅描述了 7 例β4GALT7 缺陷（spEDS-B4GALT7）患者，其临床数据表明，除身材矮小和肌肉张力减退外，桡尺骨融合、远视和认知发育迟缓可能是这种特定类型 spEDS 的标志。还认识到另外 22 例具有重叠表型的患者，即留尼汪岛的 Larsen 综合征，均携带纯合的 B4GALT7 突变。
本文报告了一位 30 岁的摩洛哥女性，她符合怀疑 spEDS 的最低标准，但缺乏桡尺骨融合和智力残疾，表现为感觉神经性听力损失和淋巴起源的肢体水肿。由于评估 spEDS 基因特异性次要标准提示了这种特定亚型，因此对 B4GALT7 进行了 Sanger 测序。突变筛查显示纯合 c.829G>T，p.Glu277*致病变异导致异常剪接。
我们的发现扩展了这种超罕见结缔组织疾病的临床和突变谱。将患者的特征与迄今为止报道的其他 spEDS 和留尼汪岛的 Larsen 综合征患者的特征进行比较，为 spEDS 分类学和该领域的临床研究提供了未来的前景。
