Perrault syndrome

Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) in both males and females, combined with ovarian dysgenesis (streak gonads) in affected females. The condition was first described by Maurice Perrault in 1951. Males with Perrault syndrome typically present with hearing loss alone, which can make diagnosis more challenging in the absence of affected female siblings. The hearing loss is bilateral and sensorineural, ranging from mild to profound, and may be present from birth or develop in early childhood. Affected females experience primary amenorrhea and infertility due to gonadal dysgenesis, with a 46,XX karyotype distinguishing the condition from Turner syndrome. Several genes have been identified as causative, including HSD17B4, HARS2, LARS2, CLPP, C10orf2 (TWNK), and ERAL1, all of which encode proteins involved in mitochondrial function or steroidogenesis. Some patients may develop additional neurological features, including progressive cerebellar ataxia, intellectual disability, and peripheral neuropathy, which has led to the distinction between Perrault syndrome type I (hearing loss and ovarian dysgenesis without neurological involvement) and type II (with neurological features). The neurological manifestations can be progressive and significantly impact quality of life. There is currently no cure or disease-modifying treatment for Perrault syndrome. Management is supportive and multidisciplinary, involving hearing aids or cochlear implants for hearing loss, hormone replacement therapy (estrogen and progesterone) for females with ovarian dysgenesis to induce secondary sexual characteristics and protect bone health, and neurological rehabilitation for those with cerebellar or peripheral nervous system involvement. Genetic counseling is recommended for affected families. Fertility is not achievable in affected females due to the absence of functional ovarian tissue, though options such as egg donation may be discussed.

Common questions about Perrault syndrome