title: Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A.
abstract: The authors describe an Italian kindred with nine individuals affected by hyperkalaemic periodic paralysis associated with paramyotonia congenita (hyperPP/PMC). Periodic paralysis was particularly severe, with several episodes a day lasting for hours. The onset of episodes was unusually early, beginning in the first year of life and persisting into adult life. The paralytic episodes were refractory to treatment. Patients described minimal paramyotonia, mainly of the eyelids and hands. All affected family members carried the threonine to methionine substitution at codon 704 (T704M) in exon 13 of the skeletal muscle voltage gated sodium channel gene (SCN4A). The association between T704M and the hyperPP/PMC phenotype has been only recently revealed. Nevertheless, such a severe phenotype has never been reported so far in families with either hyperPP or hyperPP/PMC. These data further broaden the clinical spectrum of T704M and support the evidence that this mutation is a common cause of hyperPP/PMC.
authors.affiliation: Department of Experimental Medicine and Pathology, "La Sapienza" University, Rome, Italy. f.brancati@css-mendel.it
authors.forename: F
authors.initials: F
authors.lastname: Brancati
authors.forename: E M
authors.initials: EM
authors.lastname: Valente
authors.forename: N P
authors.initials: NP
authors.lastname: Davies
authors.forename: A
authors.initials: A
authors.lastname: Sarkozy
authors.forename: M G
authors.initials: MG
authors.lastname: Sweeney
authors.forename: M
authors.initials: M
authors.lastname: LoMonaco
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
authors.forename: M G
authors.initials: MG
authors.lastname: Hanna
authors.forename: B
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D003062:Codon / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020967:Myotonic Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology; D062553:NAV1.4 Voltage-Gated Sodium Channel; D020513:Paralysis, Hyperkalemic Periodic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D012720:Severity of Illness Index; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D003062:Codon; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels