Dados do Trabalho
AUTOSOMAL DOMINANT EMERY-DREIFUSS MUSCULAR DYSTROPHY: A CASE REPORT
Apresentação do caso
Female patient, 6 years old, previously healthy, without relevant perinatal history and with adequate neuropsychomotor development, started weakness in the lower limbs at around 3 years of age, with difficulty in prolonged physical exercises and with frequent falls. Patient hospitalized for investigation of lower limb weakness and malnutrition, given current weight of 14kg (<p 0.4). She has a family history of a father with global hypotrophy and congestive heart failure, predominantly proximal weakness, difficulty in prolonged physical exercises and present Gowers sign, and a paternal grandmother who died at the age of 33 due to a heart disease. On neurological examination, patient with peripheral motor syndrome characterized by reduced strength in lower limbs (grade IV) with proximal predominance (also questioned distal component), osteotendinous reflexes abolished in lower limbs, present Gowers sign, gait with slightly widened base, tilt of the hip and with discreet raising of the feet. Collected laboratory tests that showed elevated levels of creatine phosphokinase (1257 U/L and 1074 U/L in different samples). Molecular test was collected from the patient and her father and both showed mutation in the LMNA gene, position chr1: 156,114,995, variation T > A in heterozygosis (1 copy). Despite the classification as a variant of uncertain significance, the result is compatible with the clinical condition of the patient and her father.
Emery-Dreifuss muscular dystrophy (EDMD) common phenotype is characterized by slowly progressive and low proeminent muscle weakness, accompanied by contractures of the cervical and paravertebral musculature, elbows and Achilles tendons and cardiac arrhythmia in varied proportion. Serum levels of creatinophosphokinase can be normal or slightly increased.
This condition presents a large genetic heterogeneity and can manifest X-linked, autosomal dominant and autosomal recessive inheritance. Given this large genetic heterogeneity, there is a wide variation in age of onset, severity and speed of progression of symptoms, both intra and inter-family. Autosomal Dominant Emery-Dreifuss muscular dystrophy is associated with lamins A and C gene mutations, wich supports the present case report diagnosis, correlating the patient's clinical, the family history and the variant of uncertain significance identified in the molecular test performed.
Emery-Dreifuss muscular dystrophy (EDMD) presents a large genetic heterogeneity and therefore wide phenotypic variation. Molecular testing and parental genotyping are important for proper diagnosis and identification of new pathogenic variants.
Referências (se houver)
1. Mendez-Lopez I, Worman J. Inner nuclear membrane proteins: impact on human disease. Chromosoma. 2012;121(2):153-67.
2. Bonne G, Mercuri E, Muchir A, Urtizberea A, Becane HM, Recan D, et al. Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Ann Neurol. 2000;48(2):170-80.
3. Bonne G, Leturcq F, Ben Yaou R. Emery-Dreifuss Muscular Dystrophy. 2004 Sep 29 [Updated 2019 Aug 15]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.
Emery-Dreifuss; dystrophy; autosomal dominant
Fonte de Fomento (se houver)
Declaração de conflito de interesses de TODOS os autores
Não há conflito de interesses.
IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE SÃO PAULO - São Paulo - Brasil
Ana Elisa Ribeiro Faria, Manoel Jacinto Abreu Neto, Hugo José Carvalho Garcia Santos, Laura Maria Viscardi Brighenti, Natália Josiele Cerqueira Checon, Fernanda Sá Bohn Assis, Lais Russo Carneiro Peruzzi, Roberta Caramico Pinto, Paulo Breinis