Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures: genes and variants
Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures is linked to 2 analyzed proteins (CACNA1C and CACNA1A). 4 DNA variants are known to cause it; 2 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures
CACNA1C: Voltage-dependent L-type calcium channel subunit alpha-1C
Its opening provides a major source of depolarization-triggered calcium entry in cardiomyocytes, smooth muscle, and neurons, coupling electrical activity to contraction and signaling. Pathogenic variants can cause Timothy syndrome, Brugada or long-QT phenotypes, and several neurodevelopmental disorders.
3 disease-causing and 2 uncertain variants in CACNA1C are linked to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures.
CACNA1A: Voltage-dependent P/Q-type calcium channel subunit alpha-1A
Its P/Q-type calcium current is a major trigger for neurotransmitter release at central synapses and is especially important in cerebellar circuits. Pathogenic variants cause a spectrum including familial hemiplegic migraine, episodic ataxia, spinocerebellar ataxia type 6, epilepsy, and developmental disorders.
1 disease-causing and 0 uncertain variants in CACNA1A are linked to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures.
Known disease-causing variants in Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CACNA1C G406R | 406 | I | Disease-causing (★★) |
| CACNA1A S1372L | 1372 | III | Disease-causing (★) |
| CACNA1C L657F | 657 | II | Disease-causing |
| CACNA1C L1408V | 1408 | IV | Disease-causing |
Same protein, different disease
- Long QT syndrome is also caused by CACNA1C variants; they fall mostly in different places as the Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures variants (12 disease-causing).
- Timothy syndrome is also caused by CACNA1C variants; they fall mostly in different places as the Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures variants (4 disease-causing).
- Episodic ataxia type 2 is also caused by CACNA1A variants; they fall mostly in different places as the Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures variants (93 disease-causing).
- Spinocerebellar ataxia type 6 is also caused by CACNA1A variants; they fall mostly in different places as the Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures variants (28 disease-causing).
- Migraine, familial hemiplegic, 1 is also caused by CACNA1A variants; they fall mostly in different places as the Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures variants (26 disease-causing).
- CACNA1A-related complex neurodevelopmental disorder is also caused by CACNA1A variants; they fall mostly in different places as the Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures variants (3 disease-causing).
Diseases related to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures
- Epilepsy, also linked to CACNA1A and CACNA1C
- Long QT syndrome, also linked to CACNA1C
- Episodic ataxia type 2, also linked to CACNA1A
- Cardiac arrhythmia, also linked to CACNA1C
- Migraine, familial hemiplegic, 1, also linked to CACNA1A
- Spinocerebellar ataxia type 6, also linked to CACNA1A
- Brugada syndrome, also linked to CACNA1C
- Diabetes mellitus, also linked to CACNA1C
- Disorder of sexual differentiation, also linked to CACNA1A
- Myocardial infarction, also linked to CACNA1C
- Focal epilepsy, also linked to CACNA1A
- Timothy syndrome, also linked to CACNA1C
Frequently asked questions
Which genes are linked to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures?
In CATVariant, Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures is linked to 2 analyzed proteins: CACNA1C (Voltage-dependent L-type calcium channel subunit alpha-1C) and CACNA1A (Voltage-dependent P/Q-type calcium channel subunit alpha-1A).
How many genetic variants are linked to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures?
6 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.
Which uncertain variants in Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
Download every variant as CSV · Browse all diseases · Methods · About the Center