Can I Get ARSACS Without Family History or Quebec Ancestry?

Yes. You do not need to have Quebec or French-Canadian ancestry, nor do you need a known family history of the disease, to be diagnosed with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) ^[1]. While the condition was first discovered in Quebec and remains more common there due to a historical “founder effect,” it is now recognized as a global disease ^[2]. People of all ethnicities and backgrounds can develop ARSACS ^[3]. Additionally, because of how the disease is inherited, it is completely normal for a person to be the first and only one in their family to be diagnosed ^[4].

The Quebec “Founder Effect” vs. Worldwide Reality

When ARSACS was first identified, it was found almost exclusively in the Charlevoix-Saguenay-Lac-Saint-Jean region of Quebec. In this specific region, a large number of people share a single, specific mutation in the SACS gene due to a “founder effect.” A founder effect happens when a small group of ancestors establishes a new population, and a genetic mutation from one of those original founders is passed down and becomes unusually common in the community.

However, the medical understanding of ARSACS has evolved significantly. Today, ARSACS is known to be one of the most frequent inherited ataxias worldwide ^[2]. Cases have been diagnosed in people from diverse backgrounds across the globe, including populations in Bulgaria, India, Japan, Iran, Brazil, and Uruguay ^[5][6][7].

Genetic Heterogeneity (Many Mutations, One Disease)

The reason ARSACS exists globally is due to genetic heterogeneity. This means that many different genetic mutations can cause the exact same disease. While patients in Quebec often share the same specific founder mutation, patients in other parts of the world have entirely different mutations in the SACS gene ^[8]. In fact, hundreds of unique variants (pathogenic or likely pathogenic) in the SACS gene have been discovered ^[9][10].

No matter which specific mutation a person has, the underlying problem is similar: the body loses the function of a protein called sacsin, which leads to the symptoms of ARSACS ^[11]. However, the specific mutation you have can influence how the disease presents. Because of this genetic variety, ARSACS has a broad and variable clinical spectrum; some people may experience atypical symptoms, such as an older age of onset or neuropathy without as much ataxia or spasticity ^[12][13].

Why There May Be No Family History

It is very common for someone to be diagnosed with ARSACS without any history of the disease in their family ^[4]. This is due to its autosomal recessive inheritance pattern.

For a person to develop ARSACS, they must inherit two mutated copies of the SACS gene—one from each parent. The parents, who each carry only one mutated copy, are called “carriers.” Carriers do not have ARSACS and typically show no symptoms at all.

Because carriers are healthy, the mutated gene can be passed down silently through a family for many generations. The disease only appears when two carriers have a child together, and both happen to pass on the mutated gene. This means ARSACS can seemingly appear out of nowhere, with no affected parents, grandparents, or previous generations.

When both parents are carriers, there is a 25% (1 in 4) chance with each pregnancy that the child will inherit the condition. Because of this, a genetic counselor can be a highly valuable resource to help you and your family navigate testing for siblings or discuss family planning.

What This Means for Diagnosis

Because of its name and history, some doctors may incorrectly dismiss the possibility of ARSACS if a patient is not of French-Canadian descent. If you are experiencing symptoms such as ataxia (loss of balance and coordination), spasticity (muscle stiffness in the legs), or polyneuropathy (nerve damage causing numbness, tingling, or weakness), your doctor should evaluate you based on your symptoms and clinical signs, rather than your ancestry ^[12].

For example, a highly specific sign of ARSACS is a thickening of the nerve fibers in the retina of the eye, which is a potentially useful biomarker ^[14]. You can ask your ophthalmologist or neurologist to check for this using an Optical Coherence Tomography (OCT) scan, which is a common, non-invasive imaging test.

To confirm the diagnosis, doctors look for mutations in the SACS gene, regardless of where your ancestors are from. This is typically done through targeted ataxia gene panels or broader genetic testing like whole-exome sequencing ^[15].