De Novo Chromosomes 3q and 5q Chromothripsis Leads to a 5q14.3 Microdeletion Syndrome Presentation: Case Report and Review of the Literature.

5q14.3 microdeletion syndrome (MIM#613443) is a neurodevelopmental disorder (NDD) involving copy number loss of multiple genes including Myocyte enhancer factor 2C (MEF2C) gene in the q14.3 region of chromosome 5. Chromosomes 5 and 15 chromothripsis involving 5q14.3 was previously reported in one individual with developmental epileptic encephalopathy (DEE). A complex chromothripsis between chromosomes 3, 5, 7, 9, and 18 that involved 5q14.3 was also reported in a pregnancy complicated by brain and kidney anomalies on fetal ultrasound. Here, we report chromothripsis of chromosomes 3q and 5q involving 5q14.3 in a three-year-old female with Lennox-Gastaut syndrome. The chromosomes 3q and 5q chromothripsis was found by trio genome sequencing (GS) and confirmed by fluorescent in situ hybridization (FISH). Notable clinical findings include medically refractory seizures, global developmental delay, increased fluid-attenuated inversion recovery (FLAIR) signal in the left inferior temporal gyrus, and dysmorphic features. Chromothripsis of chromosomes 3 and 5 was previously recognized in renal cell carcinomas. To the best of our knowledge, this is the first reported case of chromosomes 3q and 5q chromothripsis leading to a developmental epileptic encephalopathy (DEE) due to disruption of 5q14.3. These findings expand chromosomes 3 and 5 chromothripsis as a genomic mechanism underlying 5q14.3 microdeletion syndrome.