ABSTRACT
Fibrodysplasia ossificans progressiva (FOP) is a severe genetic disorder reported worldwide. A specific heterozygous mutation (c.617G> A; p.R206H) in the activin A type I receptor gene (ACVR1) is regarded as the genetic cause of FOP in all classically affected individuals worldwide. However, a few patients with FOP variants harbor distinct mutations in ACVR1. We screened a group of FOP Brazilian population for mutations in ACVR1. Of 16 patients with a classic FOP phenotype (10 males and 6 females, age range of 3-42 years), all had the classic mutation (p.R206H). One 21-year-old woman with a variant FOP phenotype had the previously reported c.983G> A mutation (p.G328E). Our study contributes to the understanding of the predominant FOP phenotype and genotype and suggests that variant FOP phenotypes are associated with specific mutations in ACVR1 gene.
Subject(s)
Activin Receptors, Type I/genetics , Myositis Ossificans/genetics , Adolescent , Adult , Brazil , Child , Child, Preschool , Female , Genetic Testing , Humans , Male , Middle AgedSubject(s)
Chromosome Mapping , Chromosomes, Human, X/genetics , Genes, Recessive/genetics , Muscular Atrophy, Spinal/genetics , Brazil , Child , Child, Preschool , Female , Genetic Linkage/genetics , Haplotypes/genetics , Humans , Male , Microsatellite Repeats/genetics , Muscular Atrophy, Spinal/diagnosis , Muscular Atrophy, Spinal/physiopathology , Pedigree , White People/geneticsABSTRACT
We report on clinical evaluations of Brazilian patients with misoprostol-induced arthrogryposis. All 15 patients had growth retardation, underdeveloped bones, short feet with equinovarus, rigidity of several joints with skin dimples and webs, decreased movement of legs stemming from neurologic impairment, bilateral symmetrical hypoplasia or atrophy of limb muscles, and absent tendon reflexes. Of the 15 patients, five had upper limb deformities in addition to lower limb involvement, and one had spinal cord disruption leading secondarily to segmental sensory loss and neurogenic bladder and bowel. Electroneuromyography of five patients indicated that the abnormalities were of neurogenic origin and suggestive of anterior horn cell defects. All of their mothers took 400-4,800 mcg of misoprostol orally or vaginally at 8 to 12 weeks of pregnancy. Our observations support a previously stated caution with regard to the embryotoxicity of misoprostol.
Subject(s)
Abnormalities, Drug-Induced/etiology , Abortifacient Agents, Nonsteroidal/adverse effects , Arthrogryposis/chemically induced , Embryo, Mammalian/drug effects , Misoprostol/adverse effects , Abortifacient Agents, Nonsteroidal/administration & dosage , Administration, Intravaginal , Administration, Oral , Adolescent , Adult , Child , Child, Preschool , Female , Fetal Growth Retardation/chemically induced , Humans , Infant , Infant, Newborn , Limb Deformities, Congenital/chemically induced , Male , Misoprostol/administration & dosage , PregnancyABSTRACT
BACKGROUND: Patients with upper gastrointestinal ulceration may be treated with misoprostol, but it is not recommended for pregnant women because it may stimulate uterine contractions and cause vaginal bleeding and miscarriage. Recent data from Brazil, where misoprostol is used orally and vaginally as an abortifacient, have suggested a relation between the use of misoprostol by women in an unsuccessful attempt to terminate pregnancy and Möbius' syndrome (congenital facial paralysis) in their infants. METHODS: We compared the frequency of misoprostol use during the first trimester by mothers of infants in whom Möbius' syndrome was diagnosed and mothers of infants with neural-tube defects in Brazil. All diagnoses in infants were made between January 16, 1990, and May 31, 1996, by clinical geneticists at seven hospitals who also interviewed the mothers and recorded information about the administration of misoprostol, among other data. RESULTS: We identified 96 infants with Möbius' syndrome and matched them with 96 infants with neural-tube defects. The mean age at the time of the diagnosis of Möbius' syndrome was 16 months (range, 0.5 to 78), and the diagnosis of neural-tube defects was made within 1 week of birth in most cases. Among the mothers of the 96 infants with Möbius' syndrome, 47 (49 percent) had used misoprostol in the first trimester of pregnancy, as compared with 3 (3 percent) of the mothers of the 96 infants with neural-tube defects (odds ratio, 29.7; 95 percent confidence interval, 11.6 to 76.0). Twenty of the mothers of the infants with Möbius' syndrome had taken misoprostol only orally (odds ratio, 38.8; 95 percent confidence interval, 9.5 to 159.4), 20 had taken misoprostol both orally and vaginally, 3 had taken the drug vaginally, and 4 did not report how they took the drug. CONCLUSIONS: Attempted abortion with misoprostol is associated with an increased risk of Möbius' syndrome in infants.