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Perrault Syndrome

Abstract
Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. Ovarian dysfunction ranges from gonadal dysgenesis (absent or streak gonads) manifesting as primary amenorrhea to primary ovarian insufficiency (POI) defined as cessation of menses before age 40 years. Fertility in affected males is reported as normal (although the number of reported males is limited). Neurologic features described in some individuals with Perrault syndrome include learning difficulties and developmental delay, cerebellar ataxia, and motor and sensory peripheral neuropathy.The diagnosis of Perrault syndrome is based on the clinical findings of SNHL in men and women and ovarian dysfunction in women with a 46,XX karyotype. The diagnosis is confirmed by the presence of biallelic pathogenic variants in one of six genes (CLPP, ERAL1, HARS2, HSD17B4, LARS2, or TWNK); however, in approximately 60% of individuals with Perrault syndrome identified to date, a molecular diagnosis cannot be established.Treatment of manifestations: Hearing loss should be assessed and treated by a multidisciplinary team including an audiologist and otolaryngologist. Possible interventions for those with hearing loss include special educational resources, hearing aids, vibrotactile devices, and cochlear implantation. Cochlear implantation is an option for children older than 12 months with severe-to-profound hearing loss. Primary amenorrhea is treated in adolescents in collaboration with a pediatric endocrinologist in the usual manner, first to induce puberty and then to mimic the menstrual cycle and maintain bone health. Assisted reproduction through in vitro fertilization using donor eggs is a consideration for women with gonadal dysgenesis; oocyte cryopreservation can be considered in women at risk for POI. Surveillance: Routine audiologic assessments when hearing loss is mild to moderate; no follow up or audiologic assessments when hearing loss is profound. For children with hearing impairment: monitor development For women with primary amenorrhea: during induction of puberty, follow up every three months for staging of pubertal development and adjustment of estrogen dose. For women on maintenance estrogen replacement therapy: annual follow up as well as assessment of bone density approximately every five years. Agents/circumstances to avoid: Avoid: ototoxic medication (e.g., aminoglycosides) if alternative medications are available; exposure to loud noise, which can exacerbate hearing loss. Evaluation of relatives at risk: It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from early interventions (e.g., in young children with profound hearing loss; estrogen replacement to facilitate pubertal development in females with ovarian involvement; and potential oocyte cryopreservation if POI is an issue).Perrault syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. When the pathogenic variants in the family are known, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic diagnosis are possible.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Publisher

University of Washington, Seattle
Seattle (WA)

Language

eng

PubMed ID

25254289

Citation

Newman WG, et al: Perrault Syndrome.GeneReviews®. Edited by Adam MP, et al: University of Washington, Seattle, 1993, Seattle (WA).
Newman WG, Friedman TB, Conway GS, et al. Perrault Syndrome. Edited by Adam MP, Ardinger HH, Pagon RA, et al. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993.
Newman WG & Friedman TB & Conway GS, et al. (1993). Perrault Syndrome. Edited by Adam MP & Ardinger HH & Pagon RA, et al. In GeneReviews®. Seattle (WA): University of Washington, Seattle;
Newman WG, et al. Edited by Adam MP, et al. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993.
* Article titles in AMA citation format should be in sentence-case
TY - CHAP T1 - Perrault Syndrome BT - GeneReviews® A1 - Newman,William G, AU - Friedman,Thomas B, AU - Conway,Gerard S, AU - Demain,Leigh AM, Y1 - 1993/// PY - 2018/9/6/pubmed PY - 2018/9/6/medline PY - 2014/9/26/entrez KW - ATP-dependent Clp protease proteolytic subunit, mitochondrial KW - GTPase Era, mitochondrial KW - Peroxisomal multifunctional enzyme type 2 KW - Probable histidine--tRNA ligase, mitochondrial KW - Probable leucine--tRNA ligase, mitochondrial KW - Twinkle protein, mitochondrial KW - CLPP KW - ERAL1 KW - HARS2 KW - HSD17B4 KW - LARS2 KW - TWNK KW - Perrault Syndrome N2 - CLINICAL CHARACTERISTICS: Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. Ovarian dysfunction ranges from gonadal dysgenesis (absent or streak gonads) manifesting as primary amenorrhea to primary ovarian insufficiency (POI) defined as cessation of menses before age 40 years. Fertility in affected males is reported as normal (although the number of reported males is limited). Neurologic features described in some individuals with Perrault syndrome include learning difficulties and developmental delay, cerebellar ataxia, and motor and sensory peripheral neuropathy. DIAGNOSIS/TESTING: The diagnosis of Perrault syndrome is based on the clinical findings of SNHL in men and women and ovarian dysfunction in women with a 46,XX karyotype. The diagnosis is confirmed by the presence of biallelic pathogenic variants in one of six genes (CLPP, ERAL1, HARS2, HSD17B4, LARS2, or TWNK); however, in approximately 60% of individuals with Perrault syndrome identified to date, a molecular diagnosis cannot be established. MANAGEMENT: Treatment of manifestations: Hearing loss should be assessed and treated by a multidisciplinary team including an audiologist and otolaryngologist. Possible interventions for those with hearing loss include special educational resources, hearing aids, vibrotactile devices, and cochlear implantation. Cochlear implantation is an option for children older than 12 months with severe-to-profound hearing loss. Primary amenorrhea is treated in adolescents in collaboration with a pediatric endocrinologist in the usual manner, first to induce puberty and then to mimic the menstrual cycle and maintain bone health. Assisted reproduction through in vitro fertilization using donor eggs is a consideration for women with gonadal dysgenesis; oocyte cryopreservation can be considered in women at risk for POI. Surveillance: Routine audiologic assessments when hearing loss is mild to moderate; no follow up or audiologic assessments when hearing loss is profound. For children with hearing impairment: monitor development For women with primary amenorrhea: during induction of puberty, follow up every three months for staging of pubertal development and adjustment of estrogen dose. For women on maintenance estrogen replacement therapy: annual follow up as well as assessment of bone density approximately every five years. Agents/circumstances to avoid: Avoid: ototoxic medication (e.g., aminoglycosides) if alternative medications are available; exposure to loud noise, which can exacerbate hearing loss. Evaluation of relatives at risk: It is appropriate to evaluate the older and younger sibs of a proband in order to identify as early as possible those who would benefit from early interventions (e.g., in young children with profound hearing loss; estrogen replacement to facilitate pubertal development in females with ovarian involvement; and potential oocyte cryopreservation if POI is an issue). GENETIC COUNSELING: Perrault syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. When the pathogenic variants in the family are known, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic diagnosis are possible. PB - University of Washington, Seattle CY - Seattle (WA) UR - https://www.unboundmedicine.com/medline/citation/25254289/GeneReviews®:_Perrault_Syndrome L2 - https://www.ncbi.nlm.nih.gov/books/NBK242617 DB - PRIME DP - Unbound Medicine ER -