2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A Familial Case of <em>CAMK2B</em> Mutation: Two Brothers with Severe Intellectual Disability Inherited from Healthy Father

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This case report discusses a familial case of a CAMK2B mutation, in which two brothers have severe intellectual disability inherited from their healthy father. The CAMK2B gene is responsible for encoding the β-subunit of calcium/calmodulin-dependent protein kinase II, which plays a critical role in learning and synapse plasticity. Disruption of CAMK2 autophosphorylation and impaired neuronal migration have been implicated in the pathophysiology of intellectual disability associated with CAMK2B mutations.<br /><br />The case involves a 4-year-old boy who presented with global developmental delay and autism features. He had a normal motor development but was unable to speak. His older brother, aged 6, also had severe developmental delay and autism. Both brothers had similar phenotypes and severity, including global developmental delay, no speech, autistic features, and no seizures or dysmorphism.<br /><br />The younger brother underwent brain MRI, which showed nonspecific periventricular white matter changes, and an EEG that revealed slow and disorganized background rhythm with occasional sharp waves. However, no abnormalities were found in hearing or ophthalmologic exams, and the chromosomal microarray test was normal. A targeted gene panel test confirmed a CAMK2B mutation, c.1160del p.Pro387Gln fsTer16, which was reported as a likely pathogenic mutation. Subsequent familial testing revealed the same mutation in the older brother and father, who did not exhibit any developmental or neuropsychological problems.<br /><br />This case adds to the phenotypic spectrum diversity and provides new insights into the disease mechanism of CAMK2B mutations. It highlights the need for further evaluation to understand why some individuals with pathogenic variants do not exhibit symptoms. Overall, this study underscores the importance of genetic testing in individuals with severe intellectual disability and autism to identify underlying genetic causes and potentially inform treatment strategies.

Asset Subtitle

Presenting Author - Hyo Jeong Kim, MD, PhD;

Meta Tag

Brain/Nervous System

Genotype-Phenotype Correlations

Identification of Disease Genes

Inheritance Patterns

Intellectual disability

Presenting Author Hyo Jeong Kim, MD, PhD

Keywords

CAMK2B mutation

intellectual disability

familial case

learning

synapse plasticity

neuronal migration

developmental delay

autism features

brain MRI

phenotypic spectrum diversity