Perrault syndrome
Perrault syndrome is a rare genetic condition characterized by sensorineural hearing loss in both sexes and ovarian abnormalities in affected females.
Overview
Perrault syndrome causes distinct patterns of symptoms in males and females. A hallmark of the condition is sensorineural hearing loss, which affects both ears and can be present at birth or begin in early childhood, typically worsening over time.
Symptoms
Females
Females with Perrault syndrome experience abnormalities of the ovaries (ovarian dysgenesis). Symptoms include:
- Primary amenorrhea: Failure to begin menstruation by age 16.
- Primary ovarian insufficiency: Early loss of ovarian function, where periods may stop before age 40.
- Infertility: Difficulty conceiving or inability to have biological children.
Neurological Symptoms
Both males and females may experience neurological problems, though not all affected individuals are affected. These can include:
- Intellectual disability.
- Ataxia: Difficulty with balance and coordinating movements.
- Peripheral neuropathy: Loss of sensation and weakness in the limbs.
Causes
Perrault syndrome is caused by mutations in several genes, including TWNK, CLPP, HARS2, LARS2, and HSD17B4. Many of these genes produce proteins that function in mitochondria, the structures that convert energy from food into a usable form for cells. Researchers believe that the disruption of mitochondrial energy production may underlie the symptoms of the syndrome. Mutations in the HSD17B4 gene affect peroxisomes, which are cell structures containing enzymes that break down various substances.
Inheritance
Perrault syndrome is inherited in an autosomal recessive pattern. This means that both copies of the gene in each cell must have mutations. Parents of an affected individual each carry one copy of the mutated gene but do not exhibit signs or symptoms of the condition.