以色列患有费兰-麦克德米德综合征个体的临床特征分析与医疗管理

Clinical profiling and medical management of Israeli individuals with Phelan McDermid syndrome.

作者信息

Chorin Odelia, Greenbaum Lior, Lev-Hochberg Shelly, Feinstein-Goren Neta, Eliyahu Aviva, Shani Hagit, Pras Elon, Weissbach Tal, Bolkier Yoav, Heimer Gali, Lev Dorit, Michelson Marina, Regev Miriam, Josefsberg Sagi, Batzir Nurit Assia, Shalata Adel, Spiegel Ronen, Segel Reeval, Lobel Orit, Abu-Libdeh Bassam, Shohat Mordechai, Frydman Moshe, Hady-Cohen Ronen, Pode-Shakked Ben, Rein-Rothschild Annick

机构信息

Institute of Rare Diseases, Edmond and Lily Safra Hospital for Children, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

The Danek Gertner Institute of Genetics, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

出版信息

Orphanet J Rare Dis. 2025 Mar 18;20(1):132. doi: 10.1186/s13023-025-03598-3.

DOI:10.1186/s13023-025-03598-3

PMID:40102980

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11917011/

Abstract

BACKGROUND

Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder, caused by haploinsufficiency of the SHANK3 gene. In addition to global developmental delay (GDD)/intellectual disability (ID) and autism spectrum disorder (ASD), PMS is characterized by multiple neurologic, behavioral and multisystemic manifestations.

METHODS

We aimed to establish a database of individuals with PMS in Israel. All participants underwent a detailed evaluation at a single medical center, and demographic, clinical, and genetic data were collected.

RESULTS

Seventeen unrelated individuals with PMS (mean age 10 ± 8.2 years; range, 2.5-36 years) were enrolled (10 females, 59%), all of Jewish descent. Twelve cases (70%) were caused by deletions in chromosomal region 22q13.3, including mosaicism, ring chromosome and unbalanced translocation. The other 5 (30%) cases were due to single nucleotide variants (SNVs), while the de novo SNV c.3904dup (p.Ala1302GlyfsTer69), recurred in 3 cases. All 17 participants had GDD/ID (which was severe in 10, 59%), and ASD and seizures were present in 12 (70%) and 8 (47%) individuals, respectively. Additional frequent manifestations were sleep difficulties in 13 individuals (76%), bowel movement disorders in 13 (76%), urinary track involvement in 8 (47%) and endocrine disorders in 6 (35%). Abnormal but nonspecific findings on prenatal ultrasonography were noted in 3 participants (18%). The most common perinatal complication was prolonged jaundice in 5 infants (29%). Different medical treatment modalities, including cannabidiol (CBD) full-spectrum oil extracts, were used to ease symptoms, with variable results.

CONCLUSIONS

Our experience adds to current knowledge about clinical manifestations and potential symptomatic treatment of PMS in Israel. These findings may promote clinical research and serve as infrastructure for future clinical trials.

摘要

背景

费伦 - 麦克德米德综合征（PMS）是一种神经发育障碍，由SHANK3基因单倍剂量不足引起。除了全球发育迟缓（GDD）/智力残疾（ID）和自闭症谱系障碍（ASD）外，PMS还具有多种神经、行为和多系统表现。

方法

我们旨在建立一个以色列PMS患者数据库。所有参与者均在单一医疗中心接受了详细评估，并收集了人口统计学、临床和基因数据。

结果

纳入了17名无亲缘关系的PMS患者（平均年龄10±8.2岁；范围为2.5 - 36岁）（10名女性，占59%），均为犹太裔。12例（70%）由染色体区域22q13.3缺失引起，包括嵌合体、环状染色体和不平衡易位。其他5例（30%）是由于单核苷酸变异（SNV），而新发SNV c.3904dup（p.Ala1302GlyfsTer69）在3例中复发。所有17名参与者均有GDD/ID（其中10例严重，占59%），分别有12例（70%）和8例（47%）存在ASD和癫痫发作。其他常见表现包括13例（76%）睡眠困难、13例（76%）排便障碍、8例（47%）尿路受累和6例（35%）内分泌紊乱。3名参与者（18%）产前超声检查有异常但非特异性发现。最常见的围产期并发症是5名婴儿（29%）出现黄疸持续时间延长。使用了包括大麻二酚（CBD）全谱油提取物在内的不同医学治疗方法来缓解症状，结果各异。