TY - JOUR
T1 - Novel asymptomatic CNS findings in patients with ACVR1/ALK2 mutations causing fibrodysplasia ossificans progressiva
AU - Severino, Mariasavina
AU - Bertamino, Marta
AU - Tortora, Domenico
AU - Morana, Giovanni
AU - Uccella, Sara
AU - Bocciardi, Renata
AU - Ravazzolo, Roberto
AU - Rossi, Andrea
AU - Rocco, Maja Di
PY - 2016/8/26
Y1 - 2016/8/26
N2 - Background Fibrodysplasia ossificans progressiva is an autosomal dominant disorder due to germline mutations of ACVR1/ALK2 causing progressive heterotopic endochondral ossifications. Evidence of central nervous system involvement has emerged only recently. Methods We performed an observational crosssectional brain MRI study in 13 patients (8 females, mean age 20 years), examining the relationship of clinical and neuroradiological findings. Results All patients presented small asymptomatic lesions similar to hamartomas at the level of the dorsal medulla and ventral pons, associated with minor brainstem dysmorphisms and abnormal origin of the vestibulocochlear and facial nerves. The size of the brainstem lesions did not correlate with patient's age (p=0.061), age at first flare-up (p=0.733), severity of disability ( p=0.194), history of head trauma (p=0.415) or hearing loss (p=0.237). The radiologic features and the absence of neurological symptoms were consistent with a benign process. Variable signal abnormalities and/or calcifications of the dentate nuclei were noted in all patients, while basal ganglia abnormalities were present in nine subjects. Brain calcifications positively correlated with patient's age (p<0.001) and severity of disability (p=0.002). Conclusions Our data support the hypothesis that the effects of mutation of the ACVR1/ALK2 gene are extended to the central nervous system. Brainstem hamartomatous lesions and dysmorphisms, variably associated with dentate nucleus and basal ganglia signal abnormalities and/or calcifications, may represent useful disease hallmarks.
AB - Background Fibrodysplasia ossificans progressiva is an autosomal dominant disorder due to germline mutations of ACVR1/ALK2 causing progressive heterotopic endochondral ossifications. Evidence of central nervous system involvement has emerged only recently. Methods We performed an observational crosssectional brain MRI study in 13 patients (8 females, mean age 20 years), examining the relationship of clinical and neuroradiological findings. Results All patients presented small asymptomatic lesions similar to hamartomas at the level of the dorsal medulla and ventral pons, associated with minor brainstem dysmorphisms and abnormal origin of the vestibulocochlear and facial nerves. The size of the brainstem lesions did not correlate with patient's age (p=0.061), age at first flare-up (p=0.733), severity of disability ( p=0.194), history of head trauma (p=0.415) or hearing loss (p=0.237). The radiologic features and the absence of neurological symptoms were consistent with a benign process. Variable signal abnormalities and/or calcifications of the dentate nuclei were noted in all patients, while basal ganglia abnormalities were present in nine subjects. Brain calcifications positively correlated with patient's age (p<0.001) and severity of disability (p=0.002). Conclusions Our data support the hypothesis that the effects of mutation of the ACVR1/ALK2 gene are extended to the central nervous system. Brainstem hamartomatous lesions and dysmorphisms, variably associated with dentate nucleus and basal ganglia signal abnormalities and/or calcifications, may represent useful disease hallmarks.
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U2 - 10.1136/jmedgenet-2016-104076
DO - 10.1136/jmedgenet-2016-104076
M3 - Article
AN - SCOPUS:84984622427
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
ER -