Neurological symptoms in individuals with fibrodysplasia ossificans progressiva Joseph A. KittermanJonathan B. StroberLixin KanDavid M. Rocke • Amanda CaliJeannie PeeperJennifer SnowPatricia L. R. Delai • Rolf MorhartRobert J. PignoloEileen M. ShoreFrederick S. Kaplan

Fibrodysplasia ossificans progressiva (FOP), a rare, disabling condition caused by gain-of-function muta- tions of a bone morphogenetic protein (BMP) type I receptor, leads to episodes of heterotopic ossification and resultant immobility. Neurological problems have not been associated with FOP, but neurological symptoms are com- monly reported by FOP patients. To determine the preva- lence of neurological symptoms and their characteristics in individuals with FOP, we conducted a survey of the 470 patient members of the International FOP Association (IFOPA) using a questionnaire about neurological symptoms. There were 168 responses (105 females, 63 males; age 1.5-68 years) from 30 countries representing 36 % of IFOPA members. Chronic neurological symptoms were reported by 86 (51 %). Prevalence of neuropathic pain (NP) was significantly increased (P \ 0.001) compared to the general population, and tenfold more common in females (15 %) than males (1.6 %). Of those with NP, 94 % reported other sensory abnormalities. Prevalence of recurrent severe headaches (HA) (26 %) was similar to that in the general population, but prevalence in females with FOP (36 %) was almost fourfold greater than in males. Prevalence of NP, HA, and other sensory abnormalities was substantially higher in post-pubertal females; 33 % reported symptoms worsened during menstrual periods. Worsening of neurological symptoms during FOP flare-ups was reported by 23 %. Three patients with FOP (1.8 %) reported myoclonus, a prevalence much greater than reported