对 70 名意大利 Phelan-McDermid 综合征患者样本进行临床、发育和血清素表型分析。

Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome.

机构信息

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Cantonal Psychiatric Clinic, Cantonal Socio-Psychiatric Organization (O.S.C.), Repubblica e Cantone Ticino, Mendrisio, Switzerland.

出版信息

J Neurodev Disord. 2024 Oct 3;16(1):57. doi: 10.1186/s11689-024-09572-7.

DOI:10.1186/s11689-024-09572-7

PMID:39363263

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11451156/

Abstract

BACKGROUND

Phelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD).

OBJECTIVES

To assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels.

METHODS

70 Italian PMS patients were clinically characterized by parental report, direct medical observation, and a thorough medical and psychodiagnostic protocol. Serotonin levels were measured in platelet-rich plasma by HPLC.

RESULTS

Our sample includes 59 (84.3%) cases with chr. 22q13 terminal deletion, 5 (7.1%) disruptive SHANK3 mutations, and 6 (8.6%) ring chromosome 22. Intellectual disability was present in 69 (98.6%) cases, motor coordination disorder in 65 (92.9%), ASD in 20 (28.6%), and lifetime bipolar disorder in 12 (17.1%). Prenatal and postnatal complications were frequent (22.9%-48.6%). Expressive and receptive language were absent in 49 (70.0%) and 19 (27.1%) cases, respectively. Decreased pain sensitivity was reported in 56 (80.0%), hyperactivity in 49 (80.3%), abnormal sleep in 45 (64.3%), congenital dysmorphisms in 35 (58.3%), chronic stool abnormalities and especially constipation in 29 (41.4%). Parents reported noticing behavioral abnormalities during early childhood immediately after an infective episode in 34 (48.6%) patients. Brain MRI anomalies were observed in 53 (79.1%), EEG abnormalities in 16 (23.5%), kidney and upper urinary tract malformations in 18 (28.1%). Two novel phenotypes emerged: (a) a subgroup of 12/44 (27.3%) PMS patients displays smaller head size at enrollment (mean age 11.8 yrs) compared to their first year of neonatal life, documenting a deceleration of head growth (p < 0.001); (b) serotonin blood levels are significantly lower in 21 PMS patients compared to their 21 unaffected siblings (P < 0.05), and to 432 idiopathic ASD cases (p < 0.001).

CONCLUSIONS

We replicate and extend the description of many phenotypic characteristics present in PMS, and report two novel features: (1) growth trajectories are variable and head growth appears to slow down during childhood in some PMS patients; (2) serotonin blood levels are decreased in PMS, and not increased as frequently occurs in ASD. Further investigations of these novel features are under way.

摘要

背景

Phelan-McDermid 综合征（PMS）是由位于人类 22q13.33 号染色体上的 SHANK3 基因单等位基因缺失或失活引起的，常与自闭症谱系障碍（ASD）有关。

目的

评估新样本中 PMS 患者的临床和发育表型，包括首次评估生长轨迹和血清素水平。

方法

70 名意大利 PMS 患者通过父母报告、直接医学观察和全面的医学和心理诊断协议进行临床特征描述。通过 HPLC 测量富含血小板的血浆中的血清素水平。

结果

我们的样本包括 59 例（84.3%）22q13 端缺失、5 例（7.1%）SHANK3 破坏突变和 6 例（8.6%）环状染色体 22。69 例（98.6%）存在智力障碍，65 例（92.9%）存在运动协调障碍，20 例（28.6%）存在 ASD，12 例（17.1%）存在终身双相障碍。产前和产后并发症很常见（22.9%-48.6%）。49 例（70.0%）和 19 例（27.1%）患者分别存在表达性和接受性语言缺失。56 例（80.0%）患者报告疼痛敏感性降低，49 例（80.3%）患者多动，45 例（64.3%）患者睡眠异常，35 例（58.3%）患者存在先天性畸形，29 例（41.4%）患者存在慢性大便异常，尤其是便秘。34 例（48.6%）患者的父母报告在感染后立即注意到幼儿的行为异常。53 例（79.1%）患者存在脑 MRI 异常，16 例（23.5%）患者存在脑电图异常，18 例（28.1%）患者存在肾脏和上尿路畸形。出现了两个新的表型：（a）44 例（27.3%）PMS 患者中有 12 例在入组时（平均年龄 11.8 岁）头围较小，表明头围生长减速（p<0.001）；（b）与 21 名未受影响的兄弟姐妹（P<0.05）和 432 名特发性 ASD 病例（P<0.001）相比，21 例 PMS 患者的血清素水平显著降低。