Clinical and molecular characterisation of two siblings with fibrodysplasia ossificans progressiva, from the Colombian Pacific coast (South America)

Abstract

Fibrodysplasia ossificans progressiva (FOP, MIM 135 100) is an uncommon genetic disease with a dominant autosomal germline transmission pattern; however, most cases are products of spontaneous individual mutations. It is a disabling condition that affects connective tissue, and it is distinguished by progressive heterotopic ossifications and congenital malformations of the great toes. The case of 2 brothers with progressive osseous deformation, along with ankylosis of the jaw, scoliosis and mental retardation, is presented. Blood samples were taken from each patient identifying in both of them a heterozygote mutation in exon 6 of the gene ACVR1 (c.617G>A p.Arg206His), which diagnoses the 'classic' form of FOP. The current medical treatment of this disease is early detection to avoid trauma and aggravating factors, prophylactic measures against infections and respiratory decline, symptomatic relief and physical therapy. There is currently no cure for the disease. © 2015 BMJ Publishing Group. All rights reserved

Fibrodisplasia osificante progresiva plus por una variante patogénica del gen ACVR1: Caso clínico

“…En nuestra paciente, la leucomalacia periventricular corresponde también a una anomalía de la sustancia blanca, que probablemente explica la discapacidad intelectual observada en ella. Finalmente, destacamos un reporte de dos hermanos, de origen sudamericano, portadores de la misma variante patogénica que nuestra paciente, en los que también se describe un déficit intelectual 15 . Llama la atención la mayor frecuencia compromiso cognitivo en estos 3 pacientes sudamericanos, en comparación a grandes series de otras regiones (Tabla 1).…”

Atypical Presentation of Fibrodysplasia Ossificans Progressiva: A Case Report and Review of Literature

“…FOP is a debilitating disease of progressive heterotopic bone formation in the extraskeletal tissues [ 1 ]. There are approximately 800 cases reported of this rare genetic disorder worldwide [ 6 ]. It has been reported from all parts of the world without any ethnic, racial, geographical or gender predisposition; however, a higher prevalence is reported from France [ 7 ].…”

“…Although it is characterized by spontaneous new mutations in the majority of the cases, familial cases have also been described with an autosomal dominant inheritance [ 8 ]. The symptoms typically begin in the first decade of life at a mean age of 7.1 years with a characteristic temporal and spatial pattern of episodic, painful, inflammatory soft tissue swellings [ 6 ]. The classical phenotype of FOP has two distinct physical features: formation of extraskeletal ossified masses in a progressive and episodic manner (flare-ups) following a particular anatomic pattern and presence of congenital hallux valgus with microdactyly.…”

Troubles oro-faciaux dans Fibrodysplasia ossificans progressiva. Revue systématique.

“…Pour 13 des 32 cas la possibilité de maintenir une bonne hygiène orale est mentionnée dans l'article [6, 9, 11-13, 15, 17, 20], et pour 9 de ces 13 cas [6,9,11,12,15,17,20] celle-ci est difficile à cause de la limitation d'ouverture buccale. Ce problème de contrôle de plaque dentaire entraine le développement de pathologies dentaires de type caries et abcès dans 9/32 cas [2, 6, 11-13, 15, 17] et 6 de ces cas ont des difficultés à maintenir une bonne hygiène bucco-dentaire.…”

“…Nous n'avons pu relever qu'un seul cas où l'ouverture buccale a été réduite suite aux extractions malgré que des précautions soient prises durant l'intervention [12]. [6,8,9,11,12,14,17,18,20].…”