title: Severe prognosis in a large family with hypokalemic periodic paralysis.
abstract: Hypokalemic periodic paralysis (HypoPP) is a channel disorder caused primarily by mutations in the human skeletal muscle alpha1 subunit (CACNA1S) of the dihydropyridine-sensitive calcium channel. Molecular, clinical, and biochemical studies were aimed at establishing genotype/phenotype correlations in a large Italian family affected by a severe form of HypoPP. Whereas patients with HypoPP usually show a normal life span, in this family three male patients died young, one of them from anesthetic complications resembling malignant hyperthermia. Our patients carried the c1583G>A genetic lesion (R528H), which has been associated with a mild phenotype and with incomplete penetrance in women. Surprisingly, the R528H amino acid substitution in the family presented here correlated with an unfavorable prognosis in both male and female patients. We conclude that genetic characterization is an important requirement to alert physicians about the management of similar patients, especially when anesthesia is considered.
authors.affiliation: Department of Paediatrics, University of Florence, A. Meyer Children's Hospital, Via Luca Giordano 13, 50132 Florence, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caciotti
authors.forename: Amelia
authors.initials: A
authors.lastname: Morrone
authors.forename: Raffaele
authors.initials: R
authors.lastname: Domenici
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: Donati
authors.forename: Enrico
authors.initials: E
authors.lastname: Zammarchi
mesh_terms: D000293:Adolescent; D000328:Adult; D004562:Electrocardiography; D005192:Family Health; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000235:genetics / Q000503:physiopathology; D020514:Hypokalemic Periodic Paralysis / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D018908:Muscle Weakness / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D011379:Prognosis; D012720:Severity of Illness Index