GeneReviews(®)

GeneReviews(®)

Book. 1993

Authors: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K

Abstract
CLINICAL DESCRIPTION: Action myoclonus – renal failure (AMRF) syndrome typically comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy (PME) and renal failure; however, in some instances, the kidneys are not involved. Neurologic manifestations can appear before, simultaneously, or after the renal manifestations. Disease manifestations are usually evident in the late teens or early twenties. In the rare instances in which renal manifestations precede neurologic findings, onset is usually in late childhood/early adolescence but can range to the fifth or sixth decade. Neurologic manifestations begin with tremor at rest (which is exacerbated by fine motor activities) and progress to involuntary, action-activated myoclonic jerks that involve bulbar, proximal, and distal limb muscles; involuntary spontaneous myoclonic jerks; and generalized clonic-tonic-clonic seizures. Sensorimotor peripheral neuropathy and sensorineural hearing loss can also be observed. Renal manifestations include proteinuria that can progress to nephrotic syndrome and end-stage renal disease.
DIAGNOSIS/TESTING: The diagnosis of AMRF syndrome is suspected in a previously healthy teenager or young adult with the characteristic neurologic and/or renal manifestations. The diagnosis is confirmed in individuals with biallelic (homozygous or compound heterozygous) loss-of-function pathogenic variants in SCARB2.
MANAGEMENT: Treatment of manifestations: Symptomatic pharmacologic and psychosocial support is the mainstay of care for the neurologic manifestations. Response to treatment is variable and may worsen over time, necessitating rehabilitative management. Renal insufficiency requires dialysis but response to treatment is poor, and renal transplantation is often necessary. Prevention of secondary complications: Standard measures for prevention of aspiration pneumonia and sudden unexpected death in epilepsy should be followed. Surveillance: Lifelong follow up should include regular monitoring of antiepileptic drug treatment and renal function (including urinary protein excretion, creatinine clearance, and estimated glomerular filtration rate) and periodic assessment of hearing and peripheral nerves. Agents/circumstances to avoid: Diphenylhydantoin, carbamazepine, oxcarbazepine, and possibly lamotrigine increase myoclonus and should be avoided in any individual with PME. Pregnancy management: Because some antiepileptic drugs can lead to an increased risk of malformations, growth retardation, or neurodevelopmental disabilities in exposed fetuses, standard measures for prevention of fetopathy should be followed.
GENETIC COUNSELING: AMRF 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. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk require prior identification of the SCARB2 pathogenic variants in the family.

PMID: 26677510

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