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

## TL;DR

This paper describes the clinical features and treatment approaches in 17 Israeli individuals with Phelan–McDermid syndrome, a genetic disorder affecting development and behavior.

## Contribution

The study establishes a clinical database of PMS cases in Israel and reports on the genetic and phenotypic characteristics of these individuals.

## Key findings

- Most cases were caused by chromosomal deletions or SHANK3 gene mutations.
- Common features included intellectual disability, autism, seizures, and gastrointestinal issues.
- Cannabidiol oil was used with variable success in symptom management.

## Abstract

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.

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.

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.

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.