Cohen syndrome: Can early‐onset recurrent infections and hypotonia provide early diagnosis and intervention for intellectual disability?

• Published in: International journal of developmental neuroscience 2024-12, Vol.84 (8), p.918-923
• Main Authors: Ünsel‐Bolat, Gül, Keskin‐Çelebi, Ezgi, Bolat, Hilmi
• Format: Article
• Language: English
• Subjects: Adolescent; Child; Child, Preschool; Cohen syndrome; Developmental Disabilities - genetics; Early Diagnosis; Feeding and Eating Disorders of Childhood - diagnosis; Feeding and Eating Disorders of Childhood - genetics; Female; Fingers - abnormalities; Humans; intellectual disability; Intellectual Disability - genetics; Male; Microcephaly - genetics; Muscle Hypotonia - genetics; Myopia - diagnosis; Myopia - genetics; neurodevelopmental disorder; Obesity - complications; Obesity - genetics; Retinal Degeneration; Vesicular Transport Proteins - genetics; VPS13B
• ISSN: 0736-5748; 1873-474X; 1873-474X
• DOI: 10.1002/jdn.10384

Introduction Cohen syndrome is a rare disease associated with neurodevelopmental disorders, especially intellectual disability (ID), neutropenia and recurrent infections are consistently reported in cases. Neutropenia is an important part of the syndrome, as well as ID. Homozygous variants in the VPS13B gene, located on chromosome 8q22 and containing 62 exons, have been found to cause Cohen syndrome. Cohen syndrome is commonly diagnosed when dysmorphological findings and developmental delay become more apparent. However, the identification of some findings with increasing age has caused the diagnosis of Cohen syndrome to be delayed. Methods Cases diagnosed with ID were evaluated using whole‐exome sequencing/clinical exome sequencing method. Family segregation analysis was performed using Sanger sequencing. We presented the clinical and genetic findings of three cases diagnosed with Cohen syndrome and their parents in detail. Results In this study, we presented the occurrence of symptoms in different age groups, and the prognosis of three cases carrying the VPS13B gene variants, including three different variant types: missense, frameshift and nonsense. Although our cases had different variant types, they shared important similarities on the onset period and prognosis of the symptoms. All cases presented hypotonia, difficulties in swallowing, recurrent respiratory tract infections, neutropenia, delay in motor development, ID and hyperactivity. Our cases did not have a diagnosis of autism spectrum disorder. All cases had increased willingness to engage in social communication. Conclusion We emphasize the importance of early‐onset recurrent infections and hypotonia for early diagnosis and preventive genetic counselling in Cohen syndrome. Diagnosis of Cohen syndrome was detected after the occurrence of intellectual disability (ID). We emphasize the importance of genetic testing in the presence of hypotonia and neutropenia starting in the first year of life. Early diagnosis of Cohen syndrome before intellectual disability and ocular findings occur is important for early intervention.