Homozygous mutation in ELMO2 may cause Ramon syndrome.

Area of Science:

• Genetics
• Pediatrics
• Medical Diagnostics

Background:

• Ramon syndrome is a rare genetic disorder with complex clinical manifestations.
• Understanding the genetic basis of rare syndromes is crucial for accurate diagnosis and management.

Observation:

• A family presented with a girl and her brother exhibiting intellectual disability, seizures, gingivorrhagia, craniofacial abnormalities, and skeletal anomalies.
• Radiographic examination revealed mandibular cysts, fibrous dysplasia, and significant nasopharyngeal airway narrowing due to enlarged adenoids.
• The brother had additional features including short stature, an ostium secundum, and more severe intellectual disability, ultimately succumbing to complications.

Findings:

• Clinical diagnosis of Ramon syndrome was suspected.
• Whole exome sequencing identified a novel homozygous missense mutation, p.I606S, in the ELMO2 gene in affected individuals.
• This mutation is distinct from previously reported loss-of-function mutations in ELMO2 associated with intraosseous vascular malformations (VMOS).

Implications:

• This study identifies a novel genetic cause for Ramon syndrome, linking it to the ELMO2 gene.
• The findings highlight the expanding phenotypic spectrum associated with ELMO2 mutations.
• This discovery aids in differential diagnosis and may inform future research into therapeutic strategies for ELMO2-related disorders.