Clinical and Paraclinical Aspects of Duchenne Muscular Dystrophy in Yaoundé

Edmond TINGANG WONKAM
Department of Pediatrics, The University of Yaoundé I
July, 2015
 

Abstract

Introduction and Objectives
Duchenne Muscular Dystrophy (DMD) is a muscular disease, from genetic origine, and recessive X-linked. It mainly affects boys, and women are carriers. It is due to a mutation in the DMD gene, resulting in a lack of dystrophin synthesis. It has a world incidence of 1 in 3500 live male births, and a prevalence of 1 in 8,000 male. The first clinical signs of the disease occur at a mean age of 4.09 ± 0.15 years. The
most frequently found clinical signs are proximal and distal muscle weakness, calf
hypertrophy, muscle atrophy and tendon contractures. The severity of the disease is
due to the long-term occurrence of cardiac and respiratory damage. Mutations responsible for the disease are mostly deletions, but it may also comes to duplication
or point mutations.
We proposed to conduct a study with the overall objective to describe clinical and paraclinical aspects of DMD in Yaounde; and as specific objectives, we wanted to describe the clinical manifestations of DMD, to describe the echocardiographic and electrocardiograhic abnormalities of patients suffering from DMD, and to describe the genetic profile of patients and their mothers, as well as the correlation between the genotype and the phenotype of the disease.
Methodology
We conducted a descriptive cross-sectional study during four months, from February to May 2015. Data collection included a retrospective phase from January 2008 to February 2015, and a prospective phase fromFebruary to May 2015. Clerking and physical examination of participants were done at the GOPHY; cardiac evaluation including an electrocardiogram and an echocardiography was done at the CME / FCB; genetic exams including a PCR of the DMD gene were done at the national laboratory of cytogenetic of Cape Town
Results
The mean age of our study population was 14.03 ± 5.10 years (8.08 - 25.11), for a total of 17 participants, all male, with 7 electrocardiograms acquired, 8 echocardiographies done, and 16 PCR performed. The mean age of onset of first
clinical signs was 4.59 ± 1.50 years, and the mean age at diagnosis was 12.12 ± 5.18
years
Regarding clinical abnormalities, proximal muscle weakness of the lower limbs was found in all participants, and distal muscle weakness of the lower limbs in 70% (7/10) of them. Calf hypertrophy was noted in 76.5% (13/17) of cases, a flexion contracture of hips, knees and ankles was found in 54.5%, (6/11), 53.8% (7/13) and 85.7% (12/14) of cases respectively. An atrophy of the muscles of the shoulder and pelvic girdles, of thigh, leg, arm and forearm muscles was also noted.
heart failure were noted in 2 patients, and those of nocturnal hypoventilation were found in 3 patients. Scoliosis was observed in 5 patients.
Regarding muscle enzymes, the mean blood concentration of the CK (creatine kinase) of our 17 patients was 8171.24 ± 7545.29 IU/ l (837-31872), all of them had values above the upper limit of normal. Blood levels of transaminases were above normal values in all patients regarding ALT (Alanine Aminotransaminase), and in 93.3% of them regarding AST (Aspartateaminotransaminase).
Concerning echocardiographic and electrocardiographic abnormalities, hypertrophy of the interventricular septum during diastole was observed in 37.5%
(3/8) of our patients, hypertrophic cardiomyopathy in 12.5% (1/8) of them, LV (left ventricle) systolic dysfunction in 37.5% (3/8) of them, dilated cardiomyopathy in
12.5% (1/8) of them, RV (right ventricle) dilation in 37.5% (3/8) of them, RV systolic
dysfunction in 25% (2/8) of them, and a minimal mitral regurgitation in 12.5% of
them. Sinus tachycardia was found in 28.6% (1/7) ofour patients, tall right precordial
R waves in 71.4% (5/7) of them, deep and narrow Q waves in lateral and inferior leads
in 85.7% (6 / 7) of them, and right ventricular hypertrophy in 14.3% of them.
Regarding genetic aspects, a deletion of the DMD gene was found in 45.5%
(5/11) of our patients, and a duplication in 27.3% (3/11) of them. The most affected
exons were located between exons 45 to 50. The proportion of new mutant has been estimated at 18.2% (2/11). There was no correlation either between genotype and
motor impairment, or between genotype and cardiac involvement.
Conclusion
At the end of our work, we can say that the first clinical signs of DMD in our sample occur in infancy, but the diagnosis is made late in adolescence. DMD causes motor impairments, as well as cardiac and respiratory impairments. Blood levels of muscle enzymes are high compared to normal values. Main mutations found in DMD gene are deletions and duplications. The proportion of new mutant is estimated at 18.2%.
Keywords: Duchenne Muscular Dystrophy (DMD), motor impairment, heart
Exploration, muscle enzymes, genetic profile


********************************************************************************************