Multiple palpable bony lesions: Think of Fibrodysplasia Ossificans Progressiva
שירן פינצבסקי כדיר
1,9
Ben Pode-Shakked
1,2,3,9
Shani Caspi
4,9
Nir Sherr-Lurie
5,9
Adi Dagan
6,9
Gilad Sherman
1,7,9
Asaf Vivante
1,3,8,9
Shai Padeh
1,91Pediatric Department B, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
2The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
3The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
4Hemato-Oncology Department, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
5Pediatric Orthopedic Surgery Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
6Pediatric Pulmonary Unit and the National Center for Cystic Fibrosis, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
7Pediatric Infectious Disease Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
8Pediatric Nephrology Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
9Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal-dominant disorder, found in approximately 1 in 2 million people. FOP is caused by heterozygous gain-of-function mutations in Activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) receptor, which drives extraskeletal bone formation. Generally, FOP is a progressively debilitating disease, in which malformations of the great toes are evident at birth, and progressive heterotopic endochondral ossification occurs during life. Most individuals with classic FOP experience episodes of painful inflammation of soft tissues ("flare ups"), then followed by heterotpic ossification of the muscles and related tissues.
We report of a 2 years and 8 months old male patient, born to non-consanguineous parents of Arab-Muslim descent, who presented with multiple bony lesions, involving mainly the skull, since he was 18 months of age. While several of these lesions tended to wax and wane, most remained as palpable, nontender stiff lesions. In addition, the patient presented with limited range of motion in his shoulders and arms. Upon physical examination, bilateral shortening and lateral deviation of his great toes was evident.
Following the clinical diagnosis of FOP, molecular analysis was pursued, and brought to the identification of the previously reported heterozygous c.617G>A, p.R206H mutation in the ACVR1 gene, confirming the diagnosis of FOP and enabling genetic counseling and planning of future pregnancies in the family.
This case underscores the importance of a high index of suspicion for Fibrodysplasia Ossificans Progressiva, a rare genetic disorder to be considered in the differential diagnosis of multiple bony lesions.
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