Rare Disease Day Case 2

Patient Clinical Information:

The proband is a 44-year-old male with failure to thrive, fine and gross motor delay, speech delay, learning disability, nail dysplasia, hearing loss, chronic diarrhea, headaches/migraines, and muscle weakness.

Family History:

Family history reported to include behavioral disorders, nail dysplasia, diabetes mellitus, hearing loss, and glaucoma.

Testing Ordered:

MNG Exome Proband Only Sequencing

Genetic Findings:

WAC c.139C>T (p.Arg47Ter)

Whole exome sequencing confirmed a heterozygous pathogenic nonsense variant in the WW domain-containing adaptor with coiled-coil region gene, WAC. The variant changes the arginine at amino acid position 47 to a termination codon, which is predicted to cause premature truncation of the protein.

Outcome:

The findings led to a diagnosis of DeSanto-Shinawi syndrome (OMIM: 616708), a rare neurodevelopmental disorder. Clinical features include global developmental delay, behavioral manifestations, hearing loss, ocular abnormalities, gastrointestinal issues, hypotonia, and dysmorphic features.1 DeSanto-Shinawi syndrome has been identified in less than 100 people worldwide.2 For this case, the WES studies were vital to identifying a molecular diagnosis in this adult patient.

For more information on Desanto-Shinawi syndrome, visit https://www.dessh.org/.