One gene, two inheritance patterns: a review of HSP

A plain-language summary of a published scientific study. It is educational and does not replace medical advice.

The study: Ravanbod M et al., Reviews in the Neurosciences, published online 22 October 2026[1]. A literature review. Only the abstract is freely available.

What the researchers studied

Everyone has two copies of each gene, one from each parent. In a dominant condition, one altered copy is enough for the disease to appear; in a recessive one, both copies must be altered. SPG4 is classically autosomal dominant: each child of a person with SPG4 has a 50% chance of inheriting the variant[2].

HSP genes have traditionally been sorted by a single mode of inheritance. The authors systematically reviewed studies published up to June 2026 to see which genes can cause disease both ways[1].

What they found

• Six genes are confirmed as having dual inheritance: ALDH18A1, ERLIN2, KIF1A, REEP2, UCHL1 and SPTSSA[1].
• For five more genes regarded as dominant, there is evidence that also supports a recessive form: ATL1, SPAST, RTN2, BSCL2 and SPTAN1[1].
• When both copies of a gene were altered, the disease generally started earlier and was more severe, but the link between variant and symptoms varied a lot from gene to gene[1].

What it means for families

The authors recommend that doctors look for variants on both copies of a gene even in genes regarded as "dominant only", especially in people with early onset or an unusually severe form[1]. This can change the estimated risk for other children in the family, so genetic test results are worth discussing with a clinical geneticist.

What the study does not tell us yet

This is a review of cases already published, not a study of new patients. For SPAST, the evidence for a recessive form is described as "supporting", not established[1]. For most families with SPG4, the classic dominant inheritance rule still applies[2].