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

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

Odelia Chorin  1   2   3 , Lior Greenbaum  4   5 , Shelly Lev-Hochberg  6   4 , Neta Feinstein-Goren  4 , Aviva Eliyahu  4 , Hagit Shani  4   7 , Elon Pras  4   5 , Tal Weissbach  5   7 , Yoav Bolkier  5   8 , Gali Heimer  5   9 , Dorit Lev  5   10 , Marina Michelson  5   10 , Miriam Regev  4   5 , Sagi Josefsberg  11 , Nurit Assia Batzir  12 , Adel Shalata  13   14 , Ronen Spiegel  14   15   16 , Reeval Segel  17   18 , Orit Lobel  17 , Bassam Abu-Libdeh  19 , Mordechai Shohat  5   20   21 , Moshe Frydman  4   5 , Ronen Hady-Cohen  5   10 , Ben Pode-Shakked  6   4   5 , Annick Rein-Rothschild  6   4   5
Affiliations

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

Odelia Chorin et al. Orphanet J Rare Dis. .

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.

Keywords: SHANK3; Autism spectrum disorder; Copy number variant; Intellectual disability; Phelan–McDermid syndrome; Single nucleotide variant.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board (IRB) at Sheba Medical Center. The need for written informed consent to participate was waived. Consent for publication: Not applicable. Competing interests: The authors have no competing interests to disclose.

Figures

Fig. 1
Fig. 1
FISH markers on chromosome 22. CEP = D22Z1 (red); 22q11.2 = TUPLE1 D22S451 (red); 22q12.1 = RP11-1058P22 (green); 22q13.3 = SHANK3 D22S1254. WT- wild type
Fig. 2
Fig. 2
Neurodevelopmental characteristics of individuals with Phelan-McDermid syndrome. ASD- autism spectrum disorder; DQ- developmental quotient; IQ- intellectual quotient; MRI- Magnetic resonance imaging; PMS- Phelan McDermid syndrome. * 7/ 13 individuals who underwent MRI
See this image and copyright information in PMC

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