What Your Test Results Mean:

Carriers typically show no symptoms of ZSS; however, carriers are at an increased risk of having a child with ZSS. Risk for the current or future pregnancies is dependent on your partner’s carrier status. Carrier testing of your partner is recommended in addition to consultation with a genetic counselor.

Disease Explained:

ZSS is an inherited condition that prevents the body from properly breaking down toxins and fatty acids. As a result, these substances accumulate in the body’s tissues and cause severe damage. The most severe form of ZSS is called Zellweger syndrome; infants with this disease have very poor muscle tone, skeletal abnormalities, mental retardation, feeding problems, hearing and vision loss, and seizures. These infants experience failure of multiple organs and typically do not survive for more than one year. The milder forms of ZSS are neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease. These forms are usually not evident until late infancy or early childhood and slowly develop many of the symptoms seen in individuals with Zellweger syndrome. Children with these less severe conditions often have hypotonia, vision problems, hearing loss, liver dysfunction, developmental delay, and some degree of intellectual disability. Individuals with NALD generally survive into childhood, while those with infantile Refsum disease may even reach adulthood. There is no cure for ZSS; treatment is symptomatic.

How the Genetics Works:

The clinical features of ZSS can be explained by pathogenic variants in the PEX1 gene. In general, individuals have two copies of the PEX1 gene. Carriers of ZSS have a single variant in one copy of the PEX1 gene while individuals with ZSS have variants in both copies of their genes, one inherited from each parent. Risk for two carriers to have a child with the disorder is 25%.