title: Atypical fibrodysplasia ossificans progressiva diagnosed by whole-exome sequencing.
abstract: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification of connective tissue that begins during the first decade of life. Our patient presented with intrauterine growth retardation, respiratory distress, neonatal onset soft tissue masses, bilateral hallux valgus, and congenital anomalies of the thyroid and uterus. She was initially diagnosed with atypical infantile myofibromatosis based on clinical and pathological findings. She underwent whole-exome sequencing (WES) as part of the FORGE study to identify the gene for infantile myofibromatosis; however a de novo dominant mutation in ACVR1 (NM_001105.4:c.617G>A) revised the diagnosis to FOP. This patient highlights the utility of WES as an early diagnostic tool in the investigation of patients with unusual presentations of rare diseases, thereby providing clinicians with accurate molecular diagnoses and the opportunity to tailor clinical management to improve patient care.
authors.affiliation: Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.|Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Sawyer
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Gos
authors.affiliation: Department of Pathology, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Grynspan
authors.affiliation: Division of General Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
authors.forename: Kheirie
authors.initials: K
authors.lastname: Issa
authors.affiliation: Division of Hematology/Oncology, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
authors.forename: Raveena
authors.initials: R
authors.lastname: Ramphal
authors.affiliation: Department of Diagnostic Imaging, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rotaru
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC, Canada.
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.|Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.|Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
authors.forename: Gail
authors.initials: G
authors.lastname: Graham
authors.affiliation: Division of Otolaryngology, Head and Neck Surgery, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bromwich
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D002675:Child, Preschool; D059472:Exome; D017809:Fatal Outcome; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006215:Hallux Valgus / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009221:Myositis Ossificans / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012127:Respiratory Distress Syndrome, Newborn / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D013961:Thyroid Gland / Q000002:abnormalities; D014599:Uterus / Q000002:abnormalities
chemical_list: C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I
keywords: fibrodysplasia ossificans progressiva; hallux valgus; heterotopic ossification; whole exome sequencing