What is CACNA1A?

What the gene does

The CACNA1A gene, on chromosome 19, contains the instructions to build part of a calcium channel called Ca_v2.1 (P/Q type). These channels act like tiny gates in the membrane of neurons: when they open, calcium enters the cell and the neuron releases the chemical messages that let it talk to other neurons.

The channel is especially abundant in the cerebellum, the part of the brain that coordinates movement and balance. That is why many people with CACNA1A variants have problems with coordination.

A wide spectrum

Some variants make the channel work less, others make it work too much. Depending on the variant, and even between people with the same one, symptoms can be very different: from occasional episodes in an adult to a severe condition from the first months of life.

The most frequent symptoms include:

• Ataxia: difficulties with balance and coordination, sometimes in episodes and sometimes permanent.
• Migraine, including hemiplegic migraine, where weakness on one side of the body accompanies the attack.
• Epilepsy and seizures.
• Developmental delay, especially in speech and motor skills, and intellectual disability.
• Hypotonia (low muscle tone).
• Eye movement disorders, such as nystagmus or strabismus.
• Changes in the cerebellum visible on MRI (cerebellar atrophy).

Conditions linked to CACNA1A

Doctors have historically described several conditions separately. Today we know they belong to the same family:

• Episodic ataxia type 2 (EA2): episodes of imbalance, dizziness and nausea lasting hours.
• Familial hemiplegic migraine type 1 (FHM1): migraine attacks with temporary weakness on one side of the body.
• Spinocerebellar ataxia type 6 (SCA6): slowly progressive ataxia, usually beginning in adulthood.
• Developmental and epileptic encephalopathy (DEE42): early-onset epilepsy with developmental delay.

Many children, like Martí, do not fit neatly into a single label. That is why the community speaks about CACNA1A-related disorders.

How it is diagnosed

The diagnosis is confirmed with a genetic test, usually a gene panel or exome sequencing requested by a neurologist or geneticist. It often comes after years of tests, as happened to Martí's family. Some variants are inherited from a parent; many others appear for the first time in the child (de novo).

A genetic counselling appointment helps the family understand the result and what it means for future pregnancies.

Treatment and care

There is still no cure. Care focuses on each person's symptoms and on supporting development, ideally with a coordinated team:

• Neurology, to manage epilepsy, migraine or ataxia episodes. Some symptoms respond to specific medicines that the neurologist can assess.
• Speech therapy, physiotherapy and occupational therapy.
• Psychological and educational support, at home and at school.

Research is advancing quickly. Joining patient registries and studies is one of the most useful things families can do to make treatments possible.