title: Atypical phenotypes and clinical variability in a large Italian family with DYT1-primary torsion dystonia.
abstract: The GAG deletion in the DYT1 gene usually causes a typical form of primary torsion dystonia (PTD) with early onset in a limb, rapid generalization, and sparing of cranial-cervical muscles, but atypical phenotypes have often been reported. Here, we describe a large DYT1 Italian family with phenotypically heterogeneous PTD that recapitulates all the atypical features associated with the DYT1 mutation, including late age at onset, focal or segmental phenotypes, onset or spreading of dystonia to the cranial-cervical muscles. Of 38 healthy family members, 15 also carried the DYT1 mutation, with an estimated penetrance of 21%. A literature review of atypical familial cases of DYT1-PTD showed that late onset, cervical involvement, and limited progression of dystonia are features frequently seen in DYT1 families. However, nearly all of these atypical patients fall within at least one of the clinical categories that best predict the DYT1 carrier status, namely, early onset, onset in a limb, and family history positive for early-onset dystonia.
authors.affiliation: Department of Neurological and Visual Sciences, Neurological section, University of Verona, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Gambarin
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Paolo
authors.initials: P
authors.lastname: Liberini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Barrano
authors.forename: Alberto
authors.initials: A
authors.lastname: Bonizzato
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Moretto
authors.forename: Mirta
authors.initials: M
authors.lastname: Fiorio
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Nicola
authors.initials: N
authors.lastname: Smania
authors.forename: Antonio
authors.initials: A
authors.lastname: Fiaschi
authors.forename: Michele
authors.initials: M
authors.lastname: Tinazzi
mesh_terms: D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D004421:Dystonia / Q000175:diagnosis / Q000235:genetics*; D004422:Dystonia Musculorum Deformans / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009460:Neurologic Examination; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D018832:Molecular Chaperones; C108175:TOR1A protein, human