{Reference Type}: Case Reports
{Title}: Novel SYNGAP1 Variant in an Adult Individual Affected by Intellectual Disability and Epilepsy: A Cold Case Solved through Whole-Exome Sequencing.
{Author}: Rosti G;Boeri S;Divizia MT;Pisciotta L;Mancardi MM;Lerone M;Cerminara M;Servetti M;Spirito G;Vozzi D;Fontana M;Gustincich S;Nobili L;Zara F;Puliti A;
{Journal}: Mol Syndromol
{Volume}: 14
{Issue}: 5
{Year}: 2023 Oct
{Factor}: 1.494
{DOI}: 10.1159/000529408
{Abstract}: <B>UNASSIGNED: </B>Nowadays, whole-exome sequencing (WES) analysis is an essential part in the diagnostic pathway of individuals with complex phenotypes when routine exams, such as array-CGH and gene panels, have proved inconclusive. However, data on the diagnostic rate of WES analysis in adult individuals, negative to first-tier tests, are lacking. This is because initiatives with the aim of diagnosing rare diseases focus mainly on pediatric unsolved cases.<BR><B>UNASSIGNED: </B>We hereby present a 45-year-old woman with severe intellectual disability, previous psychomotor developmental delay, behavioral disorders, stereotypies, nonconvulsive epilepsy, and dysmorphisms. The proband first came to our attention when she was 4 years old (in 1982); since then, she has undergone several clinical and instrumental assessments, without reaching a genetic diagnosis. At last, through WES analysis, a novel de novo variant in SYNGAP1 was found. The clinical characteristics associated with SYNGAP1 are similar to those presented by the proband.<BR><B>UNASSIGNED: </B>The variant is predicted to be deleterious and is most probably the cause of the proband's phenotype. The perseverance of the clinicians and the family allowed us to reach a diagnosis in a woman with a more than 30-year history of clinical evaluations, instrumental assessments, and genetic tests. This diagnosis was of significant relevance in genetic counseling for family members and the proband herself.