Search

Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single-gene disorders is under-characterized. To explore the genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort of patients with CP.We performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non-cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms). We characterized motor phenotypes, ascertained medical comorbidities, and classified brain MRIs. We analyzed WES data using an institutional pipeline.We included 50 probands in this analysis (20 females, 30 males). Twenty-four had cryptogenic CP, 20 had non-cryptogenic CP, five had CP masquerader classification, and one had unknown classification. Hypotonic-ataxic subtype showed a difference in prevalence across the classification groups (p = 0.01). Twenty-six percent of participants (13/50) had a pathogenic/likely pathogenic variant in 13 unique genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, ATL1), including one patient with two genetic disorders (ACADM, PDHX) and two patients with a SPAST-related disorder. The CP masquerader category had the highest diagnostic yield (n = 3/5, 60%), followed by the cryptogenic CP category (n = 7/24, 29%). Fifteen percent of patients with non-cryptogenic CP (n = 3/20) had a Mendelian disorder on WES.WES demonstrated a significant prevalence of Mendelian disorders in individuals clinically diagnosed with CP, including in individuals with known CP risk factors.

Purposeof Review: Etiological investigations for adults with intellectual disability (ID) pose a special challenge to many adult neurologists. The adaptability of pediatric guidelines for workup of ID to adult populations has not been clearly established. We review the current recommendations on etiological workup of ID in children and adults and provide initial guidance for adult neurologists who care for people with ID of unknown etiology.Recent Findings:Etiological workup, including genetic testing, is recommended in people with ID of unknown origin. Workup should be guided by a thoughtful history and physical exam, which can help identify certain causes of ID.Summary:Specific diagnoses may help guide management and surveillance of comorbid conditions in people with ID. Etiological investigations of adults with ID include genetic and metabolic testing, and brain imaging in the appropriate clinical setting.

Individuals with intellectual and developmental disabilities (IDDs) are among our most medically vulnerable neurologic patient population. As such, they are at particular risk of psychosocial and medical harm during the coronavirus disease 2019 (COVID-19) pandemic. Here, we highlight strategies to decrease potential infectious exposures and ensure continued optimal neurologic care for individuals with IDD during the COVID-19 pandemic. Finally, in a climate of potential medical resource restriction, we offer some suggestions for advocacy on behalf of individuals with IDD.