Atypical phenotypes and clinical variability in a large Italian family with DYT1-primary torsion dystonia.
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.
Gambarin
Mattia
M
Department of Neurological and Visual Sciences, Neurological section, University of Verona, Italy.
Valente
Enza Maria
EM
Liberini
Paolo
P
Barrano
Giuseppe
G
Bonizzato
Alberto
A
Padovani
Alessandro
A
Moretto
Giuseppe
G
Fiorio
Mirta
M
Dallapiccola
Bruno
B
Smania
Nicola
N
Fiaschi
Antonio
A
Tinazzi
Michele
M
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
D018832:Molecular Chaperones; C108175:TOR1A protein, human