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Prevalence of Perrault syndrome (PS) is unknown but over 100 patients whose diagnosis has been confirmed by molecular analysis have been reported so far, with an approximately 2:1 female to male ratio. The disease is most likely underdiagnosed, especially in the male population where it remains undetected in the absence of an affected sister.

Perrault syndrome is subdivided in two types. Type 1, static, presents with deafness and ovarian dysgenesis in females. Type 2 presents with additional neurological, and rarely, muscular or renal manifestations. Mean age at diagnosis is 26 years old, and based on presentation with delayed puberty in females with sensorineural deafness. Hearing defects (mean age at diagnosis of 7 years) were noted in all but one of the reported cases. The hearing loss is sensorineural and generally bilateral, prelingual, and asymmetric, with a variable severity (mild to profound) even in affected patients from the same family. It is classically an auditory neuropathy (with presence of otoacoustic emissions initially). Ovarian dysgenesis has been reported in all female cases, but no gonadal dysgenesis has been reported in males. Amenorrhea is generally primary, but can also be secondary. Neurological features are inconstant, progressive, and of variable severity; they include cerebellar dysfunction with ataxia, sensitive or sensitive-motor neuropathy, and less frequently, developmental delay.

PS is a heterogeneous disease. Biallelic, homozygotous, or compound heterozygous mutations in 8 genes have been identified, but molecular analysis remains inconclusive in half of the patients. PS is due to alterations of mitochondrial (CLPP, ERAL1, HARS2, LARS2, RMND1, TWNK genes) or metabolic functions (HSD17B4, GGSP1 genes). Outside of disease forms presenting with constant neurologic disorders (which sometimes precede hearing loss) associated with mutations in TWNK, or exceptional renal symptoms associated with RMND1 mutations, there is no correlation between genotype and phenotype.

Hearing loss is evaluated by otoacoustic emissions (OAE) and auditory evoked potentials (AEP). CT scans reveal that the hearing loss is not associated with temporal bone malformations. Hormonal tests (LH, FSH, AMH levels), which are required in deaf females with no signs of puberty at 11 years old, reveal hypergonadotropic hypogonadism. Pelvic examinations reveal absent ovaries or streak gonads, and a very hypoplasic uterus. Neurologic investigations reveal reduced nerve conduction velocities, and cerebral MRI may show a nonspecific white matter hypersignal or cerebellar atrophy. Genetic analysis can reveal causal mutations in half of patients.

Turner syndrome is the main differential diagnosis.

Prenatal diagnosis is possible when the pathogenic variants have previously been identified in a family member.

Treatment and follow-up should be multidisciplinary, including audiologists, endocrinologists, neurologists and psychologists. Hearing aids or cochlear implants may help for the hearing defect. Puberty induction and ovarian preservation should be discussed with the family.

Life expectancy is normal for patients with Perrault syndrome type 1. Outcome is variable in patients with Perrault syndrome type 2 who present with progressive neurological disease.