Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder that gradually affects a person’s movement, balance, vision, speech, and thinking abilities. The signs and symptoms of this condition typically become noticeable in mid-to-late adulthood. Many individuals affected by PSP, and their families, often wonder whether this complex condition can be passed down through generations. This article explores the nature of PSP, distinguishing between its more common occurrences and the rare instances where genetics play a role.
Sporadic PSP: The Common Scenario
The vast majority of progressive supranuclear palsy cases are considered sporadic, meaning they occur without any known genetic link or family history of the disorder. For over 95% of people diagnosed with PSP, the condition is not inherited from their parents, nor is it likely to be passed on to their children. This common scenario provides reassurance to many families, as it indicates a very low risk for other family members, including siblings or children, to develop the condition. The emergence of sporadic PSP is currently understood to involve a combination of unknown factors that lead to its development in an individual.
Familial PSP: The Rare Exception
While most cases are sporadic, progressive supranuclear palsy can, in very rare circumstances, show a pattern of familial inheritance. In a small number of families worldwide, PSP has been observed to affect multiple members across different generations. When PSP does run in families, it can follow an autosomal dominant pattern of inheritance.
This means that only one copy of an altered gene in each cell is sufficient to cause the disorder. Such familial clusters are exceptionally uncommon, with mutations in a gene coding for a microtubule protein identified in only a few tens of families globally. This inherited form means a genetic predisposition is present and can be traced through the family lineage.
Associated Genetic Risk Factors
Progressive supranuclear palsy is characterized by the abnormal accumulation of a protein called tau within brain cells, leading to their gradual damage. This condition is categorized as a “tauopathy” due to these protein clumps. The microtubule-associated protein tau (MAPT) gene is closely linked to PSP, as mutations in this gene can disrupt the normal structure and function of the tau protein.
Certain variations, or haplotypes, of the MAPT gene are known to increase an individual’s susceptibility to developing PSP. The H1 haplotype, for instance, is considered the strongest genetic risk factor identified for PSP, potentially increasing the risk by more than fivefold. Possessing these genetic risk factors, like the H1 haplotype, does not directly cause PSP; rather, they increase the likelihood of its development.
While the H1 haplotype generally confers risk, some of its subhaplotypes can be associated with a reduced risk of PSP, and the H2 haplotype often has a protective effect. The presence of abnormal tau is also observed in individuals without MAPT gene mutations. Because these genetic factors only indicate an increased risk and do not guarantee the onset of the disease, genetic testing for PSP is generally not recommended for sporadic cases.