Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy.

Heterozygous de novo variants in the eukaryotic elongation factor EEF1A2 have previously been described in association with intellectual disability and epilepsy but never functionally validated. Here we report 14 new individuals with heterozygous EEF1A2 variants. We functionally validate multiple variants as protein-damaging using heterologous expression and complementation analysis.

Rare presentation of 6q16.3 microdeletion syndrome with severe upper limb reduction defects and duodenal atresia.

We present a patient with a 17.31 MB interstitial deletion of 6q16.3-6q22.

Tuberous sclerosis complex: Five new things.

Purpose Of Review: Tuberous sclerosis complex (TSC) is a variably expressed neurocutaneous genetic disorder characterized by hamartomatous growths in multiple organ systems. Neurologic involvement often confers the most severe symptoms, and can include epilepsy, increased intracranial pressure from hydrocephalus, intellectual deficits, and autism. The purpose of this review is to provide a neurologically focused update in the diagnosis and treatment of these complications in patients with TSC.

Ebstein anomaly, left ventricular non-compaction, and early onset heart failure associated with a de novo α-tropomyosin gene mutation.

Ebstein anomaly of the tricuspid valve (EA) can be associated with left ventricular non-compaction (LVNC), a rare congenital cardiomyopathy. We report a 2 year-old female with EA and severe tricuspid regurgitation, LVNC, pulmonary hypertension, and chronic biventricular systolic heart failure, who died during evaluation for cardiac transplantation. Gene panel testing revealed a heterozygous de novo missense mutation in TPM1, which encodes the cardiac sarcomeric thin filament protein α-tropomyosin.

Early-onset heart failure, alopecia, and cutaneous abnormalities associated with a novel compound heterozygous mutation in desmoplakin.

Mutations in the desmosomal protein desmoplakin have been associated with various conditions affecting the skin and heart. The prototype is Carvajal syndrome, characterized by cardiomyopathy, woolly hair, palmoplantar keratoderma (PPK), and skin fragility. We report the case of a 3-year-old boy presenting with severe left-sided heart failure with a preceding history of cutaneous abnormalities including congenital alopecia, PPK, nail dystrophy, and follicular hyperkeratosis on the extensor surfaces.