Abstract

Prader-Willi syndrome (PWS) is a rare genetic syndrome, caused by the loss of expression of the paternal chromosome 15q11-q13 region. Over the past years, many cases of patients with characteristics similar to PWS, but without a typical genetic aberration of the 15q11-q13 region, have been described. These patients are often labelled as Prader-Willi-like (PWL). PWL is an as-yet poorly defined syndrome, potentially affecting a significant number of children and adults. In the current clinical practice, patients labelled as PWL are mostly left without treatment options. Considering the similarities with PWS, children with PWL might benefit from the same care and treatment as children with PWS. This review gives more insight into the pheno- and genotype of PWL and includes 86 papers, containing 368 cases of patients with a PWL phenotype. We describe mutations and aberrations for consideration when suspicion of PWS remains after negative testing. The most common genetic diagnoses were Temple syndrome (formerly known as maternal uniparental disomy 14), Schaaf-Yang syndrome (truncating mutation in the MAGEL2 gene), 1p36 deletion, 2p deletion, 6q deletion, 6q duplication, 15q deletion,15q duplication, 19p deletion, fragile X syndrome and Xq duplication. We found that the most prevalent symptoms in the entire group were developmental delay/intellectual disability (76%), speech problems (64%), overweight/obesity (57%), hypotonia (56%) and psycho-behavioral problems (53%).In addition, we propose a diagnostic approach to patients with a PWL phenotype for (pediatric) endocrinologists. PWL comprises a complex and diverse group of patients, which calls for multidisciplinary care with an individualized approach.

中文翻译：

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Prader-Willi 样表型和基因型的光谱：文献综述

摘要

Prader-Willi 综合征 (PWS) 是一种罕见的遗传综合征，由父系染色体 15q11-q13 区域的表达缺失引起。在过去几年中，已经描述了许多具有与 PWS 相似特征但没有典型的 15q11-q13 区域遗传异常的患者病例。这些患者通常被标记为 Prader-Willi 样 (PWL)。PWL 是一种尚未明确定义的综合征，可能影响大量儿童和成人。在目前的临床实践中，标记为 PWL 的患者大多没有治疗选择。考虑到与 PWS 的相似性，患有 PWL 的儿童可能会受益于与患有 PWS 的儿童相同的护理和治疗。这篇综述对 PWL 的表型和基因型进行了更深入的了解，包括 86 篇论文，包含 368 例具有 PWL 表型的患者。我们描述了在阴性检测后仍怀疑 PWS 时需要考虑的突变和畸变。最常见的基因诊断是 Temple 综合征（以前称为母亲单亲二体 14）、Schaaf-Yang 综合征（MAGEL2 基因截断突变）、1p36 缺失、2p 缺失、6q 缺失、6q 重复、15q 缺失、15q 重复、19p缺失、脆性 X 综合征和 Xq 重复。我们发现整个组中最普遍的症状是发育迟缓/智力障碍 (76%)、言语问题 (64%)、超重/肥胖 (57%)、肌张力减退 (56%) 和心理行为问题 (53% ). 此外，我们为（儿科）内分泌科医生提出了一种对具有 PWL 表型的患者的诊断方法。PWL 包括复杂多样的患者群体，