DOI: 10.5958/j.2319-5886.3.2.

109

International Journal of Medical Research & Health Sciences

www.ijmrhs.com Volume 3 Issue 2 (April - Jun) Coden: IJMRHS th Received: 17 Feb 2014 Revised: 20th Mar 2014
Case report

Copyright @2014 ISSN: 2319-5886 Accepted: 22nd Mar 2014

DUCHENNE MUSCULAR DYSTROPHY DIAGNOSED BY DYSTROPHIN GENE DELETION TEST: A CASE REPORT *Rathod Kishor G1, Dawre Rahul M1 , Kamble Milind B1,Tambe Saleem H1
1

Department of Pediatrics, Dr. Shankarrao Chavan Government Medical College, Nanded, Maharashtra, India

*Corresponding author email: [email protected] ABSTRACT Duchenne muscular dystrophy (DMD) is an X-linked recessive disease affecting 1 in 36006000 live male births. A muscle biopsy is not necessary if a genetic diagnosis is secured first, particularly as some families might view the procedure as traumatic. DMD occurs as a result of mutations (mainly deletions) in the dystrophin gene (DMD; locus Xp21.2). Mutations lead to an absence of or defect in the protein dystrophin, which results in progressive muscle degeneration leading to loss of independent ambulation. Ninety percent of out frame mutations result in DMD, while 90% of in-frame mutations result in BMD. Electron microscopy is not required to confirm DMD. Genetic testing is mandatory irrespective of biopsy results. But the muscle biopsy is not required if the diagnosis is secured first by genetic testing. Keywords: Duchenne Muscular Dystrophy, dystrophin gene deletion test. INTRODUCTION DMD is an X-linked disease that affects 1 in 36006000 live male births.1 Affected individuals are unable to run and jump properly due to proximal muscle weakness, which also results in the use of the classic Gowers' manoeuvre when arising from the floor. Most patients are diagnosed at approximately 5 years of age, when their physical ability differs markedly from their peers. Respiratory and cardiac complications emerge, and without intervention, the mean age at death is around 19 years. Nonprogressive cognitive dysfunction might also be present.2 DMD occurs as a result of mutations (mainly deletions) in the dystrophin gene. Mutations lead to an absence of or defect in the protein dystrophin, which results in progressive muscle degeneration and loss of ambulation by the age of 13 years.3 CASE REPORT A 7 years old male child, second by order of birth, born of non consanguineous marriage, brought with complaints of frequent falls while walking since 2 years. And difficulty in standing from sitting position since 1 year. Birth history was uneventful. Milestones were achieved as per age till 5 years of age. On admission general condition was good, speech normal, no mental retardation; calf hypertrophy was present, Gowers sign positive, and tone normal. Power grades in various muscle groups of the lower limbs were as shown in Table 1. Truncal weakness was present. Neck flexors were weak as compared to extensors. Investigation: Hb 11.4 gm%, total leukocyte count 6600/cmm platelets- 3.55 lac/cmm.CPK-12600 IU/Lit. 506 Rathod et al., Int J Med Res Health Sci. 2014;3(2):506-508

Table 1: Grading of power in various muscle groups of lower limb. Region Muscle group Right side Left side Hip Flexors 4 4 Extensors 3 3 Abductors 3 3 Knee Extensors 4 4 Flexors 4 4 Ankle Dorsi-flexion 4 4 Plantar flexion 5 5 Reflexes Knee reflex Absent Absent Ankle reflex + + Muscle biopsy was not done because relatives were not ready. Molecular test for deletion of dystrophin gene showed Deletion has seen of exons 45, 46, 47, 48, 49and 50. These deletions indicating out frame mutations. This is along with the age of the patient is consistent with DMD. (90% of out frame mutations result in DMD, while 90% of in-frame mutations result in BMD). Clinical manifestations: Infants rarely symptomatic, though some manifest by mild hypotonia. Early gross motor milestones are usually achieved at the proper ages or may be mildly delayed. Poor head, holding in infancy may be the earliest sign of weakness. In toddlers lordotic posture is to compensate for gluteal weakness. A Gowers sign and Trendelenburg gait is often evident by age 5 or 6 yr. Some are confined to a wheelchair by 7 yr of age; most patients normal till 10 yr of age. With orthotic prostheses, physiotherapy, and sometimes minor surgery (Achilles tendon lengthening), most are able to walk until age 12 yr. Apart from postponing the psychological depression ambulation even for as little as 1 hour per day prevents scoliosis. The weakness progresses continuously into the 2nd decade. The distal muscles are relatively well preserved. Respiratory involvement like weak and ineffective cough, frequent respiratory infections, and decreasing respiratory reserve, with pharyngeal weakness leading to aspiration, nasal regurgitation of liquids, and nasal voice quality. Contractures involving the ankles, knees, hips, and elbows are common. Pseudohypertrophy of the calves and wasting of thigh muscles are classic features of DMD. It is due to hypertrophy of some muscle fibers, infiltration of muscle by fat, and proliferation of collagen. After the calves, the next most common site Rathod et al.,

of muscular hypertrophy is the tongue, followed by muscles of the forearm. The voluntary sphincter muscles rarely become involved. Unless ankle contractures are severe deep tendon reflexes remain well preserved. The knee deep tendon reflexes may be present until about 6 yr of age, but are less brisk than the ankle jerks and are eventually lost. In the upper extremities, the brachioradialis reflex is usually stronger than the biceps or triceps brachii reflexes. Cardiomyopathy is seen in 5080% of patients and its severity of cardiac involvement does not necessarily correlate with the degree of skeletal muscle weakness. Some patients die early of severe cardiomyopathy while still ambulatory; others in terminal stages of the disease have well-compensated cardiac function. Smooth muscle dysfunction, particularly of the gastrointestinal tract, is a minor, but often overlooked, feature. Mental retardation is common, although only 20 30% have an IQ <70. The majority has learning disabilities that still allow them to function in a regular classroom, particularly with remedial help. A few patients are profoundly mentally retarded, but there is no correlation with the severity of the myopathy. Epilepsy is slightly more common than in the general pediatric population. Dystrophin is expressed in brain and retina, as well as in striated and cardiac muscle, though the level is lower in brain than in muscle. This distribution may explain some of the CNS manifestations. Abnormalities in cortical architecture and of dendritic arborization may be detected neuropathologically; cerebral atrophy is demonstrated by MRI late in the clinical course. The degenerative changes and fibrosis of muscle constitute a painless process. Myalgias and muscle spasms do not occur. Calcinosis of muscle is rare. Death occurs usually at about 1820 yr of age. The common causes of death are respiratory failure in sleep, intractable heart failure, pneumonia, or occasionally aspiration and airway obstruction.4 DIAGNOSIS An open muscle biopsy is necessary if the differential diagnosis includes DMD among other types of muscular dystrophy, so that adequate tissue will be available for further analysis. A needle biopsy may be appropriate if testing is only for DMD. The key tests done on biopsy are immunocytochemistry and 507 Int J Med Res Health Sci. 2014;3(2):506-508

immunoblotting for dystrophin.3 Electron microscopy is not required to confirm DMD. Genetic testing is mandatory after a positive biopsy. However, if genetic testing is negative for mutation, but creatine kinase concentrations are increased and signs or symptoms consistent with DMD are present, then the next necessary diagnostic step is to do a muscle biopsy. This is also the case if there is a family history of DMD and a suspicion of the diagnosis, but no family mutation is known.5 Treatment: Gluco-corticoids slow the decline in muscle strength and function in DMD. The goal is to preserve ambulation and decrease in later respiratory, cardiac, and orthopaedic complications. Other dietary supplements, such as coenzyme Q10, carnitine, aminoacids (glutamine, arginine), anti-oxidants (fish oil, vitamin E, green-tea extract), and others, are being used. Expert doesnt recommend the use of these supplements due to lack of supportive data.6 CONCLUSION A muscle biopsy is not necessary if a genetic diagnosis is secured first, particularly as some families might view the procedure as traumatic. Electron microscopy is not required to confirm DMD. However, if genetic testing has been done and no mutation identified, but creatine kinase concentrations are increased and signs or symptoms consistent with DMD are present, then the next necessary diagnostic step is to do a muscle biopsy. REFERENCES 1. Drousiotou A, Ioannou P, Georgiou T. Neonatal screening for Duchenne muscular dystrophy: a novel semi quantitative application of the bioluminescence test for creatine kinase in a pilot national program in Cyprus. Genet Test. 1998; 2: 55-60 2. Poysky J. Behavior patterns in Duchenne muscular dystrophy: report on the Parent Project Muscular Dystrophy behavior workshop 89 of December2006, Philadelphia, USA. Neuromuscul Disord .2007; 17: 986-94 3. Hoffman EP, Brown RH, Kunkel LM. Dystrophi n: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987; 51:919-28 4. Harvey B Sarnat. Duchenne and Becker Muscular Dystrophies. In: Kligman, Behrman, Jenson,

Stanton, editors. Nelson Textbook of Pediatrics. Elsivier. 2007;18th ed: 2540-41 5. Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol.2003; 2: 731-740. 6. Katharine B, Richard F, David JB, Laura EC, Paula RC, Linda C. Diagnosis and management of Duchenne muscular dystrophy. The Lancet Neurology. 2010;9:77-93

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