Hôpital Marin AP-HP, Unité Prader-Willi, Hendaye, France.
J Intellect Disabil Res. 2010 Mar;54(3):204-15. doi: 10.1111/j.1365-2788.2010.01251.x. Epub 2010 Feb 2.
Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by developmental abnormalities leading to somatic and psychological symptoms. These include dysmorphic features, impaired growth and sexual maturation, hyperphagia, intellectual delay, learning disabilities and maladaptive behaviours. PWS is caused by a lack of expression of maternally imprinted genes situated in the 15q11-13 chromosome region. The origin is a 'de novo' deletion in the paternal chromosome in 70% of the cases and a maternal uniparental disomy in 25%. The two main genotypes show differences, notably regarding cognitive and behavioural features, but the mechanisms are not clear. This study assessed cognitive impairment in a cohort of adults with genetically confirmed PWS, analysed their profiles of cognitive strengths and weaknesses, and compared the profiles in terms of genotype.
Ninety-nine male and female adults participated, all inpatients on a specialised unit for the multidisciplinary care of PWS. The Wechsler Adult Intelligence Scale (WAIS-III) was administered to all patients in identical conditions by the same psychologist. Eighty-five patients were able to cope with the test situation. Their scores were analysed with non-parametric statistical tools. The correlations with sex, age and body mass index were explored. Two genotype groups were compared: deletion (n = 57) and non-deletion (n = 27).
The distribution of intelligence quotients in the total cohort was non-normal, with the following values (medians): Full Scale Intelligence Quotient (FSIQ): 52.0 (Q1:46.0; Q3:60.0), Verbal Intellectual Quotient (VIQ): 53.0 (Q1:48; Q3:62) and Performance Intellectual Quotient (PIQ): 52.5 (Q1:48; Q3:61). No correlation was found with sex, age or body mass index. Comparison between groups showed no significant difference in FSIQ or VIQ. PIQ scores were significantly better in the deletion group. The total cohort and the deletion group showed the VIQ = PIQ profile, whereas VIQ > PIQ was observed in the non-deletion group. The subtest scores in the two groups showed significant differences, with the deletion group scoring better in three subtests: object assembly, picture arrangement and digit symbol coding. Some relative strengths and weaknesses concerned the total cohort, but others concerned only one genotype.
We documented a global impairment in the intellectual abilities of a large sample of French PWS patients. The scores were slightly lower than those reported in most other studies. Our data confirmed the previously published differences in the cognitive profiles of the two main PWS genotypes and offer new evidence to support this hypothesis. These results could guide future neuropsychological studies to determine the cognitive processing in PWS. This knowledge is essential to improve our understanding of gene-brain-behaviour relationships and to open new perspectives on therapeutic and educational programmes.
普拉德-威利综合征（PWS）是一种罕见的遗传疾病，其特征是发育异常导致躯体和心理症状。这些症状包括畸形特征、生长和性成熟受损、食欲过盛、智力迟缓、学习障碍和适应不良行为。PWS 是由于位于 15q11-13 染色体区域的母源印记基因表达缺失引起的。其病因 70%的病例为父源染色体“新生”缺失，25%的病例为母源单亲二倍体。两种主要基因型存在差异，特别是在认知和行为特征方面，但机制尚不清楚。本研究评估了一组经基因证实的 PWS 成年患者的认知障碍，分析了他们的认知优势和劣势特征，并比较了基因型之间的特征。
99 名男性和女性成年人参与了研究，均为 PWS 多学科治疗的专门病房的住院患者。所有患者均由同一位心理学家在相同条件下接受韦氏成人智力量表（WAIS-III）测试。85 名患者能够应对测试情况。他们的分数用非参数统计工具进行分析。探讨了与性别、年龄和体重指数的相关性。比较了两组基因型：缺失组（n=57）和非缺失组（n=27）。
整个队列的智商分布是非正态的，以下值（中位数）：全量表智商（FSIQ）：52.0（Q1：46.0；Q3：60.0）、言语智商（VIQ）：53.0（Q1：48；Q3：62）和操作智商（PIQ）：52.5（Q1：48；Q3：61）。与性别、年龄或体重指数均无相关性。两组间 FSIQ 或 VIQ 无显著差异。缺失组 PIQ 评分明显更好。整个队列和缺失组表现出 VIQ=PIQ 特征，而非缺失组则表现出 VIQ>PIQ。两组的子测验分数存在显著差异，缺失组在三个子测验中得分更好：物体组装、图片排列和数字符号编码。一些相对优势和劣势涉及整个队列，但另一些仅涉及一种基因型。
我们记录了大量法国 PWS 患者的智力能力存在全面障碍。分数略低于大多数其他研究报告的分数。我们的数据证实了两种主要 PWS 基因型认知特征的先前发表差异，并提供了新的证据支持这一假设。这些结果可以指导未来的神经心理学研究，以确定 PWS 中的认知加工。这些知识对于加深我们对基因-大脑-行为关系的理解以及为治疗和教育计划开辟新的前景至关重要。
