2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-NBEA-related neurodevelopmental disease: expansion of the phenotype and second patient with clinical images

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The document discusses a case study of a patient with NBEA-related neurodevelopmental disorder. The patient is a 16-year-old girl with a history of Ehlers Danlos, hypermobile type, fine motor delays, and borderline grades in school. She has a family history of hypermobility issues, heart murmur, dyslexia, bipolar depression, ADHD, and learning difficulties. <br /><br />The patient has a history of developmental delays, including delayed walking, and currently exhibits gait abnormalities and hypotonia. She also has memory problems, difficulties with anger management, and symptoms suggestive of bipolar depression. She demonstrates autistic behaviors, particularly with social cues. <br /><br />Physical examination reveals facial dysmorphia, including prominent eyebrows, limited maxillary underdevelopment, a thin upper vermillion border, smooth philtrum, and mandibular prominence. She also has scoliosis, genu valgum, lordosis, mild scissor gait, and joint hypermobility. <br /><br />Genetic testing identified a variant in the NBEA gene (c.8309 C>T p.P2770L). This variant has not been previously reported and was classified as a variant of uncertain significance. In silico analysis suggests a deleterious effect on protein structure/function. The effectiveness of seizure control in altering the developmental trajectory of patients with NBEA variants is noted. <br /><br />The document also discusses NBEA and its role in neurodevelopmental disorders. NBEA is a neuronal protein implicated in autism, epilepsy, and other neurodevelopmental disorders. It regulates synaptic formation and functioning through the trafficking of postsynaptic proteins. De novo variants in NBEA have been reported in patients with neurodevelopmental disorders, with variable findings including behavioral abnormalities, hypotonia, microcephaly, and movement disorders. Most of these patients also have epilepsy with early onset during childhood. <br /><br />The case study highlights the need for further research to understand the role of NBEA in autism, epilepsy, and other neurodevelopmental disorders. The resemblance in facial features between patients with NBEA variants suggests a possible connection that should be explored.

Asset Subtitle

Presenting Author - Saihari S. Dukkipati, PhD; Co-Author - Lois Starr, MD, PhD, FAAP, FACMG;

Meta Tag

Brain/Nervous System

Exome sequencing

Neuroscience

Co-Author Lois Starr, MD, PhD, FAAP, FACMG

Presenting Author Saihari S. Dukkipati, PhD

Keywords

NBEA-related neurodevelopmental disorder

case study

gait abnormalities

hypotonia

bipolar depression

autistic behaviors

facial dysmorphia

genetic testing

neurodevelopmental disorders

epilepsy