ABSTRACT
Non-dystrophic myotonias are a group of rare neuromuscular diseases linked to SCN4A or CLCN1. Among the subtypes, myotonia permanens, associated with the Gly1306Glu variant of SCN4A, is a relatively less frequent but more severe form. Most reports of non-dystrophic myotonias describe European populations. Therefore, to expand the genetic and phenotypic spectrum of this disorder, we evaluated 30 Chilean patients with non-dystrophic myotonias for associated variants and clinical characteristics. SCN4A variants were observed in 28 (93%) of patients, including 25 (83%) with myotonia permanens due to the Gly1306Glu variant. Myotonia permanens was inherited in 24 (96%) patients; the mean age of onset was 6 months, and the initial symptoms were orbicularis oculi myotonia in 17 (74%) patients and larynx myotonia in 12 (52%) patients. The extraocular muscles were involved in 11 (44%) patients, upper limbs in 20 (80%), and lower limbs in 21 (84%). Thirteen (52%) patients experienced recurrent pain and 10 (40%) patients reported limitations in daily life activities. Carbamazepine reduced myotonia in eight treated patients. The high frequency of the Gly1306Glu variant in SCN4A in Chilean patients suggests a founder effect and expands its phenotypic spectrum.
Subject(s)
Myotonia/genetics , NAV1.4 Voltage-Gated Sodium Channel/genetics , Adolescent , Adult , Child , Chile , Cohort Studies , Female , Founder Effect , Humans , Infant , Male , Mutation , Myotonic Disorders/genetics , Young AdultABSTRACT
Fibrodysplasia ossificans progressiva (FOP) or myositis ossificans, is a genetic disease, with a prevalence of 1 in 2.000.000. It is caused by pathogenic variants in ACVR1 gene and characterized by soft tissue heterotopic ossification, starting in the second decade of life. It is associated to early mortality caused by respiratory complications. It evolves in flare-ups, triggered by soft tissue injuries; therapy is symptomatic, using analgesia, steroids and diphosphonates. We report a 12-year-old female with left renal agenesis, hallux valgus and intellectual disability, presenting with a six months history of thoracic kyphosis, tender nodules in the thorax, and rigidity of right elbow and left knee. Clinical examination revealed dysmorphic facial features. A magnetic resonance showed heterotopic ossification nodules, which was confirmed with spinal radiography. These findings prompted the diagnosis of FOP. Pain treatment was started, and prednisone was used during flare-ups. The ACVR1 gene was analyzed and a pathogenic variant, p. Arg206His, was found, confirming the diagnosis of FOP.
Subject(s)
Myositis Ossificans/diagnostic imaging , Anti-Inflammatory Agents/therapeutic use , Child , Chile , Female , Humans , Magnetic Resonance Imaging , Myositis Ossificans/drug therapy , Myositis Ossificans/genetics , Ossification, Heterotopic/diagnostic imaging , Ossification, Heterotopic/drug therapy , Ossification, Heterotopic/genetics , Prednisone/therapeutic useABSTRACT
Fibrodysplasia ossificans progressiva (FOP) or myositis ossificans, is a genetic disease, with a prevalence of 1 in 2.000.000. It is caused by pathogenic variants in ACVR1 gene and characterized by soft tissue heterotopic ossification, starting in the second decade of life. It is associated to early mortality caused by respiratory complications. It evolves in flare-ups, triggered by soft tissue injuries; therapy is symptomatic, using analgesia, steroids and diphosphonates. We report a 12-year-old female with left renal agenesis, hallux valgus and intellectual disability, presenting with a six months history of thoracic kyphosis, tender nodules in the thorax, and rigidity of right elbow and left knee. Clinical examination revealed dysmorphic facial features. A magnetic resonance showed heterotopic ossification nodules, which was confirmed with spinal radiography. These findings prompted the diagnosis of FOP. Pain treatment was started, and prednisone was used during flare-ups. The ACVR1 gene was analyzed and a pathogenic variant, p. Arg206His, was found, confirming the diagnosis of FOP.
