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J Clin Med Res. 2016 Mar;8(3):246-53. doi: 10.14740/jocmr2465w. Epub 2016 Jan 26.

The Diversity of the Clinical Phenotypes in Patients With Fibrodysplasia Ossificans Progressiva.

Journal of clinical medicine research

Ali Al Kaissi, Vladimir Kenis, Maher Ben Ghachem, Jochen Hofstaetter, Franz Grill, Rudolf Ganger, Susanne Gerit Kircher


  1. 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.
  2. 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.
  3. Department of Pediatric Orthopedic Surgery, Children Hospital, Tunis, Tunisia.
  4. Orthopedic Hospital of Speising, Pediatric Department, Vienna, Austria.
  5. Institute of Medical Chemistry, Medical University of Vienna, Austria.

PMID: 26858800 PMCID: PMC4737038 DOI: 10.14740/jocmr2465w


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.

CONCLUSION: 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.

Keywords: ACVR1 gene mutation; Congenital hallux valgus; FBN1 gene mutation; Fibrodysplasia ossificans progressiva; Imaging; Monophalangia; Progressive joint limitations


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