Double Trouble: Phelan-McDermid syndrome and Robinow syndrome

Abstract

Introduction. The comorbidity of genetic disorders presents a significant diagnostic and therapeutic challenge. Overlapping phenotypic features can complicate differential diagnosis. This article presents a case of so-called «double trouble» – the co-occurrence of Robinow syndrome and Phelan-McDermid syndrome phenotypes in a single patient.
Objective. To identify the genetic cause of the complex phenotype in the proband, as well as to discuss the challenges of differential diagnosis and management strategies for such cases.
Methods. The proband is a 2-year-old girl. The main complaints included delayed psychomotor and speech development, skeletal abnormalities, epilepsy, and facial dysmorphisms. The family history is not burdened with hereditary pathology. The parents are nonconsanguineous. Studies were conducted to determine the concentrations of 7-dehydrocholesterol and 8-dehydrocholesterol (GC-MS), karyotyping, FISH, and whole-genome sequencing.
Results. The proband was found to have a pathogenic variant c.257A>G (p.Tyr86Cys) in the WNT5A gene, associated with autosomal dominant Robinow syndrome, as well as a large deletion of the terminal region of the long arm of chromosome 22, including the SHANK3 gene, associated with Phelan-McDermid syndrome.
Conclusions. This case highlights the diagnostic challenges of comorbid genetic disorders and emphasizes the importance of using modern genetic analysis methods.