Perrault Syndrome

Perrault syndrome (PS) is characterized by the association of ovarian dysgenesis in females with sensorineural hearing impairment. In more recent PS reports, some authors have described neurologic abnormalities, notably progressive cerebellar ataxia and intellectual deficit.

Epidemiology

Prevalence is unknown but 34 patients with PS (28 females and 6 males) from 15 different families have been reported so far. However, the syndrome is probably underdiagnosed: hypogonadism is not a feature in males and in the absence of an affected sister the syndrome remains undetected.

Clinical description

Mean age at diagnosis is 22 years following presentation with delayed puberty in females with sensorineural deafness. Hearing defects were noted in all but one of the reported cases (mean age at diagnosis of 8 years). The hearing loss is always sensorineural and bilateral but the severity is variable (mild to profound), even in affected patients from the same family. Ovarian dysgenesis has been reported in all female cases but no gonad defects are detected in males. Amenorrhea is generally primary but secondary amenorrhea has also been reported. Delayed growth (height below the third percentile) was reported in half the documented cases. The exact frequency of the neurological abnormalities is unknown, but nine females and two males (16-37 years old) lacking neurological abnormalities have been reported. Neurological signs are progressive and generally appear later in life, however, walking delay or early frequent falls have been noted in young PS patients. Common neurological signs are ataxia, dyspraxia, limited extraocular movements, and polyneuropathy. Some cases with scoliosis have also been reported.

Etiology

Mutations in the following genes have been excluded: GJB2 (responsible for the most frequent form of isolated hearing loss), FOXL2 (involved in premature ovarian failure) and POLG, FRDA, AOA1 (implicated in ataxia or ophthalmoplegia). Karyotype is normal. The variability in the presence of the neurological symptoms may indicate that PS is a heterogeneous disease.

Diagnostic methods

Diagnosis is made on the basis of the clinical signs and further investigations: CT scans revealing that the hearing loss is not associated with temporal bone malformations; hormonal tests revealing hypergonadotropic hypogonadism in females; pelvic examinations revealing absent ovaries or streak gonads, and a very hypoplasic uterus, and neurologic investigations revealing reduced nerve conduction velocities. Cerebral MRI may show a nonspecific white matter hypersignal or cerebellar atrophy.

Differential diagnosis

Turner syndrome is the principle differential diagnosis (see this term).

Genetic counseling

Transmission of PS is probably autosomal recessive but no gene locus or mitochondrial mutations have been identified to date.

Management and treatment

Treatment and follow-up should be multidisciplinary including audiologists, endocrinologists and neurologists. Hearing aids or cochlear implants may be of benefit for the hearing defect.

Prognosis

Life expectancy is normal. Outcome with treatment is very variable, depending on the association with other features, in particular the presence of neurologic disease.