Background Fibrodysplasia ossificans progressiva (FOP, MIM #135100), is an extremely rare genetic disorder characterized by progressive formation of extraskeletal bone (heterotopic endochondral ossification, HEO) and specific congenital malformation of the great toes. A heterozygous activating mutations in the gene encoding ACVR1 (a bone morhogenic protein type I receptor) are responsible for the symptoms of the disease.
Objectives We present a 3-year-old girl with severe form of FOP and atypical ACVR1 mutation (G356D).
Results Our patient was born at term to healthy no consanguineous parents. There was no significant medical history in her family. On postpartum physical examination bilateral deformation of toes and thumbs were found. Middle phalanges of fingers II, IV at both hands were underdeveloped. There was structural heart malformation (ASD II, PDA). The first sign of soft tissue ossification was noted after routine vaccination in the first month of life. Initially the symptoms were misdiagnosed. In the following months, a number of extra-bone ossification lesions were developing at the neck, back, shoulders and forearms, most frequently after minor injuries. All of them were preceded by painful inflammatory soft tissues swellings, of which some regressed spontaneously. The clinical diagnosis of FOP has been established at the age of 15 months, confirmed by the presence of atypical heterozygous ACVR1 mutation (1067G>A; G356D) discovered by sequencing of ACVR1 gene. So far, G356D mutation has been reported in connection to a milder phenotype of FOP. However, in our patient, the course of the disease is severe, rapidly progressive, leading to significant disability.
Conclusions Although extremely rare, FOP should always be considered in differential diagnosis of children presenting with heterotopic endochondral ossification, especially coexisting with congenital malformation of toes. In the present case we demonstrate the severe end of spectrum of classic clinical features of FOP in an individual with atypical ACVR1 mutation (1067G>A; G356D).
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Disclosure of Interest None Declared