title: The Diversity of the Clinical Phenotypes in Patients With Fibrodysplasia Ossificans Progressiva.
abstract: BACKGROUND
  The clinical presentation, phenotypic characterization and natural history of fibrodysplasia ossificans progressiva (FOP) are diverse and the natural history of the disease is, to a certain extent, different from one patient to another.
  
  
  METHODS
  In a series of 11 patients (eight girls and three boys, aged 0 - 16 years), variable clinical presentations were the landmarks of these patients. At birth, all of our patients manifested short great toes in a valgus position. Marfan syndrome was the suggested diagnosis in three children aged 3 - 8 years and in two pre-adult patients. Clinical symptoms were torticollis, painful spine, and painful and marked limitation of the pelvic movements. Monophalangia associated with Marfanoid habitus was also a prevailing clinical presentation.
  
  
  RESULTS
  Our results were based upon the appearance of the earliest pathologic feature of FOP in correlation with the clinical presentation. In infants (0 - 1 year), three infants showed congenital hallux valgus and stiff spine. In the pediatric group (3 - 8 years), all children showed no mutation in the fibrillin-1 (FBN1) gene. Their prime presentation was a progressive torticollis with simultaneous development of erythematous subfascial nodules, most commonly located on the posterior neck and back. In pre-adult group (10 - 16 years), four patients presented with monophalangia associated with painful movements because of the progressive heterotopic ossification of the spine and the weight bearing zones and marked elevation of alkaline phosphatase. Genetic confirmation has been performed in six patients who manifested the classical mutation of the ACVR1 gene. The rest of the patients were assessed via clinical and radiographic phenotypes.
  
  
  CONCLUSIONS
  The early recognition of FOP can be performed by noticing the short halluces and thumbs at early infancy and later on the high alkaline phosphatase activity in areas of heterotopic ossification. Misconception of FOP is of common practice and eventually unnecessary diagnostic biopsies might deteriorate the progression of the condition. The detection of ACVR1 gene mutation was a confirmatory procedure. Interestingly, the timing of the onset and the location of progressive heterotopic ossifications were extremely variable and confusing among our group of patients.
authors: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, First Medical Department, Hanusch Hospital, Vienna, Austria; Orthopedic Hospital of Speising, Pediatric Department, Vienna, Austria.
authors: Ali
authors: A
authors: Al Kaissi
authors: Pediatric Orthopedic Institute n.a. H. Turner, Department of Foot and Ankle Surgery, Neuroorthopedics and Systemic Disorders, Parkovaya str., 64-68, Pushkin, Saint-Petersburg, Russia.
authors: Vladimir
authors: V
authors: Kenis
authors: Department of Pediatric Orthopedic Surgery, Children Hospital, Tunis, Tunisia.
authors: Maher
authors: M
authors: Ben Ghachem
authors: Orthopedic Hospital of Speising, Pediatric Department, Vienna, Austria.
authors: Jochen
authors: J
authors: Hofstaetter
authors: Orthopedic Hospital of Speising, Pediatric Department, Vienna, Austria.
authors: Franz
authors: F
authors: Grill
authors: Orthopedic Hospital of Speising, Pediatric Department, Vienna, Austria.
authors: Rudolf
authors: R
authors: Ganger
authors: Institute of Medical Chemistry, Medical University of Vienna, Austria.
authors: Susanne Gerit
authors: SG
authors: Kircher
keywords: ACVR1 gene mutation; Congenital hallux valgus; FBN1 gene mutation; Fibrodysplasia ossificans progressiva; Imaging; Monophalangia; Progressive joint limitations