De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures.
Beryl Royer-Bertrand, Marine Jequier Gygax, Katarina Cisarova and 20 others
PMID 34702355WHAT IT FOUND
Seven patients with de novo CACNA1E variants presented with global developmental delay, speech delays, and social deficits, but lacked the severe epilepsy and motor impairments seen in larger cohorts.
One patient showed improved sleep and bladder control after topiramate treatment.
Key findings
01Patients with de novo CACNA1E variants presented with global developmental delay, marked speech and language delays, and social behavioral deficits, but without severe neuromotor deficits or epileptic seizures.
02Four of the seven patients experienced developmental regression unrelated to seizures, with loss of previously acquired vocabulary and communicative skills.
03In one patient, topiramate treatment was associated with improvement in motor hyperkinesia, social contact, and regain of nocturnal sphincter control, though behavioral disorders and development showed no additional effect.
STILL TO COME
How it was doneWhat they foundWhat it means for PTsWhat it means for OTsWhat it means for SLPs
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What it does not show
The study is a small case series of only seven patients, which limits the generalizability of the findings. No functional studies were performed to confirm the pathogenic mechanism (gain-of-function vs loss-of-function) of the identified variants. Data collection relied on a matchmaking platform (GeneMatcher), leading to variability in clinical assessments and diagnostic criteria across different centers. The younger patients may still develop seizures later in life, so the absence of epilepsy is not definitive for the entire lifespan. The effect of topiramate was observed in only one patient and could have been coincidental or part of natural development.
Declared interests
The research was supported by the N.I.H. (Extramural) and Non-U.S. Gov't grants. No commercial conflicts of interest are explicitly detailed in the provided text snippets beyond funding sources.
The easy way to misread this
Do not assume that CACNA1E variants always cause severe epilepsy and profound disability. This series shows a milder phenotype with developmental delay and regression but no seizures, which may lead to missed diagnoses if clinicians only test for CACNA1E in epileptic patients.