title: Novel asymptomatic CNS findings in patients with ACVR1/ALK2 mutations causing fibrodysplasia ossificans progressiva.
abstract: 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.
  
  
  
  We performed an observational cross-sectional brain MRI study in 13 patients (8 females, mean age 20 years), examining the relationship of clinical and neuroradiological findings.
  
  
  
  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).
  
  
  
  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.
authors: Neuroradiology Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Mariasavina
authors: M
authors: Severino
authors: Rare Disease Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Marta
authors: M
authors: Bertamino
authors: Neuroradiology Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Domenico
authors: 0000-0002-5621-4046
authors: D
authors: Tortora
authors: Neuroradiology Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Giovanni
authors: G
authors: Morana
authors: Neuropsychiatry Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Sara
authors: S
authors: Uccella
authors: Medical Genetics Unit, Istituto Giannina Gaslini, Genova, Italy.|Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova, Genova, Italy.
authors: Renata
authors: R
authors: Bocciardi
authors: Medical Genetics Unit, Istituto Giannina Gaslini, Genova, Italy.|Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova, Genova, Italy.
authors: Roberto
authors: R
authors: Ravazzolo
authors: Neuroradiology Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Andrea
authors: A
authors: Rossi
authors: Rare Disease Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Maja
authors: M
authors: Di Rocco
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009221:Myositis Ossificans / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I
keywords: Brain MRI; Clinical genetics; Diagnostics; Fibrodysplasia Ossificans Progressiva