Addressing the Diagnostic Odyssey for Adults With Neurodevelopmental Disabilities: Case Study of an Individual With Mandibulofacial Dysostosis With Microcephaly

Abstract

Whole exome sequencing (WES) has been widely used in the pediatric setting to increase diagnostic yield, provide treatment options, and to estimate reoccurrence risks. However, there is limited knowledge regarding the utility of this technology in adults with neurodevelopmental disabilities. We present a 23-year-old male diagnosed with autism spectrum disorder, intellectual disability, cleft palate, micrognathia, microcephaly, bifid uvula, conductive hearing impairment, and hypotonia. The patient had several dysmorphic features including epicanthal folds, bulbous nasal tip, bilateral lop ear deformities, and tapered digits. His previous genetic workup includes negative Fragile X, microarray, FISH, and sub-telomeric testing. He has had several reconstructive surgeries and a cleft palate repair. Despite suspecting a genetic syndrome, WES testing was never completed due to its novelty and cost. Recently, WES testing found that he harbors a pathogenic variant in the EFTUD2 gene (c.1705 C>T) which is associated with Mandibulofacial Dysostosis With Microcephaly (MFDM). This variant was found to be de novo, providing the family with a refined reoccurrence risk. Testing adults can provide insight into the treatment options for young families and a better understanding of the course of the condition. Thus, this case adds to the literature on the management and spectrum of symptoms as well as highlights the importance of re-evaluating adult patients. Further research should be conducted to determine the utility and cost-effectiveness for WES testing in this population.