Phelan–McDermid Syndrome: Expanding the Phenotype

El-Bassyouni, Hala T.; Eid, Ola M.; Ismail, Samira; El-Ruby, Mona O.; Ashaat, Engy A.; Mahrous, Rana; Hussein, Shymaa H.; Kamel, Alaa K.; Zaki, Maha S.; Hamed, Khaled; Soliman, Doaa R.; Mohamed, Ramy; Mohamed, Amal M.

doi:10.21608/MXE.2023.287525

Phelan–McDermid Syndrome: Expanding the Phenotype

Document Type : Original Article

Authors

¹ Department of Clinical Genetics, National Research Centre, Egypt.

² Department of Human Cytogenetics, National Research Centre, Egypt.

³ Department of Pediatrics, Faculty of Medicine, Benha University, Benha, Egypt.

⁴ Department of Biological Anthropology, National Research Centre, Egypt.

10.21608/MXE.2023.287525

Abstract

Background: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder recognized by developmental delay, mild dysmorphisms, autism spectrum disorder (ASD), and intellectual disability (ID). Objectives: The aim of this work was to describe an Egyptian cohort of PMS patients and investigate the phenotype-genotype correlation. Patients and Methods: Four patients with dysmorphic features, delayed milestones and autistic behavior were subjected to clinical examination, karyotyping, Fluorescence In Situ Hybridization (FISH), Multiplex ligation dependent probe amplification (MLPA) Chromosomal microarray (CMA) analysis. Results: One patient presented with microcephaly. Echocardiography showed patent foramen ovale (PFO) and bilateral abnormal superior vena cava (SVC) in one patient. MRI revealed vermal hypoplasia and kinked corpus callosum in one patient and cerebral atrophy in another patient. All patients disclosed ID, while autistic behavior was noted in 3 patients. Karyotype detected no abnormality in 3 patients, while the fourth revealed ring chromosome 22. MLPA identified heterozygous deletion at 22q13 in 2 patients. FISH and CMA detected heterozygous deletion at 22q13 in one patient. Relation between patient’s results and types of graft used showed no statistically significant differences between them. Conclusion: Our study highlighted the occurrence of ASD in individuals with PMS due to SHANK3 deletion, though, some individuals could compensate for such deletions. This report expanded the PMS phenotype and described some anomalies that to the best of our knowledge have not been previously described.

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