Facioscapulohumeral muscular dystrophy: hearing loss and other atypical features of patients with large 4q35 deletions.
OBJECTIVE
Patients affected by facioscapulohumeral muscular dystrophy (FSHD) with unusual large 4q35 deletions tend to present atypical features in early childhood. We explored the clinical presentation of patients with a very short 4q35 fragment (10-13 kb) focusing on hearing loss, a still debated FSHD extra-muscular manifestation.


METHODS
We evaluated six cases with EcoRI 4q35 fragment size ranging from 10 to 13 kb. Assessment of hearing function was carried out by otoscopy, audiometry and auditory-evoked brainstem responses (ABR). Patient data were compared with those of 28 similar subjects reported in the literature.


RESULTS
Sensorineural hearing loss was found in four patients, who presented infantile-onset dystrophic phenotype. Hearing loss was associated with mental retardation in three of them and with epilepsy in two. Auditory ability of the other two cases was mildly impaired. If findings related to 28 similar cases reported to date are also considered, auditory impairment appears evident in 68% of these subjects.


CONCLUSIONS
Hearing loss represents a characteristic feature of FSHD patients with a large 4q35 deletion. Moreover, when considering only cases with 10-11 kb, it appears to be associated with early-onset dystrophic phenotype, with mental retardation (92%) and possibly with epilepsy (58%).
Trevisan
C P
CP
Department of Neurosciences, University of Padua, Padua, Italy. carlopietro.trevisan@unipd.it
Pastorello
E
E
Tomelleri
G
G
Vercelli
L
L
Bruno
C
C
Scapolan
S
S
Siciliano
G
G
Comacchio
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D001299:Audiometry; D002869:Chromosome Aberrations; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D015897:Comorbidity; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D055815:Young Adult