Case Files Pediatrics, (LANGE Case Files) 4th Ed.


Parents worry about their 4-year-old son’s ability to walk. He began walking at 16 months, but he was clumsy and fell frequently; they were reassured by another pediatrician that he would “outgrow it.” He remains clumsier than his peers, falls during simple tasks, and has developed a “waddling” gait. Within the last month he has experienced increasing difficulty arising from a sitting position on the floor.

Image What is the most likely diagnosis?

Image What is the diagnostic test of choice?

Image What is the mechanism of disease?

ANSWER TO CASE 42: Muscular Dystrophy

Summary: A 4-year-old boy has delayed walking, a waddling gait, clumsiness, and proximal muscle weakness.

• Most likely diagnosis: Muscular dystrophy (MD), probably Duchenne type.

• Diagnostic test: DNA peripheral blood analysis or immunohistochemical detection of abnormal dystrophin on a muscle biopsy tissue section.

• Mechanism of disease: Duchenne MD is an X-linked recessive trait. The abnormal gene is at the Xp21.2 locus and encodes for an aberrant form of the protein dystrophin.



1. Know the presentation of children with inherited MD.

2. Understand the inheritance pattern of the common MDs.

3. Understand the progression of the MD.


This 4-year-old boy exhibits classic Duchenne muscular dystrophy (DMD) signs: waddling gait and progressive proximal muscle weakness. Initial testing includes serum creatine kinase (CK) assessment and DNA analysis of peripheral blood for diagnosis. After the diagnosis of DMD, the family is introduced to support organizations and is offered genetic counseling. Ongoing cardiac evaluation for the development of cardiomyopathy is routine. Medical therapy is supportive.


Muscular Dystrophy


GOWER SIGN: A description of patients with proximal muscle weakness arising to a standing position. The legs are brought under the torso and weight is shifted to the hands and feet. The hands are walked toward the feet and up the thighs as the patient attempts to rise.

TRENDELENBURG GAIT:A pelvic waddling gait from proximal muscle weakness.


DMD is the most common hereditary neuromuscular degenerative disease,with an incidence of 1 in 3300 male births; 30% of cases are new mutations. It is the most severe progressive primary myopathy of childhood.

DMD usually is asymptomatic during infancy, with normal or mildly delayed developmental milestones, but by 3 to 5 years of age patients have increasing lumbar lordosis (gluteal weakness), frequent falling, difficulty climbing stairs, hip waddle, and proximal muscle weakness (Gower sign). Muscular enlargement, caused by hypertrophy of muscle fibers and infiltration of fat and collagen proliferation, causes calf, gluteal, and deltoid muscle pseudohypertrophyand a “woody” feel of the affected area. Contractures of hip flexors, heel chords, and iliotibial bands develop, limiting joint range of motion. Cardiomyopathywith ECG findings on the precordial leads of tall R waves on the right and deep Q waves on the left can be seen. Nonprogressive intellectual impairment is common (mean IQ 80); brain atrophy can be seen on brain CT.

Patients generally become wheelchair dependent by 10 and 13 years of age and have rapid progression of scoliosis after the loss of ambulation. Distal muscles remain functional, permitting adequate manual dexterity. Respiratory muscle involvement and the scoliosis result in diminished pulmonary function and recurrent pulmonary infections. Oropharyngeal dysfunction can lead to aspiration, further compromising respiratory capacity.

DNA blood analysis is diagnostic in two-thirds of casesMuscle biopsy tissue testing for abnormal dystrophin can be performed when blood samples are not diagnostic. Muscle biopsy findings include endomysial connective tissue proliferation, inflammatory cell infiltrates, areas of regeneration interspersed with areas of degeneration, and areas of necrosis. Other laboratory findings include elevated CK levels. This enzyme is elevated before clinical signs (helpful in diagnosing familial cases); in 80% of cases, female carriers have elevated CK levels. Electromyogram findings reveal myopathy, but patients with Becker MD also have a genetic defect at the Xp21.2 locus, resulting in similar, but less severe, disease.

Treatment consists of medical therapies to slow disease progression. Orthopedic intervention, including bracing and tendon lengthening, can prolong the duration of ambulation and slow the progression of scoliosis. Caution must be exercised with surgical interventions, as these patients are prone to hyperthermia with anesthesia. Physiotherapy may delay the onset of contractures but is not intended for muscle strengthening because significant exercise can hasten muscle degeneration. The American Academy of Neurology and the Child Neurology Society recommend offering affected boys age 5 and older treatment with prednisone (optimal dosing 0.75 mg/kg/d). It is important that the potential benefits and risks of steroid therapy are discussed with the patient and family. All DMD patients have some degree of cardiomyopathy; it does not correlate with the degree of skeletal involvement. Thus, routine cardiac evaluation is required. Early cardiac dysfunction may be responsive to digoxin.

Respiratory failure is often the cause of death. Pulmonary infections are treated early and aggressively; exposure to respiratory illnesses should be limited when possible. Routine immunizations and pneumococcal vaccine are supplemented with yearly influenza vaccine.

The nutritional status of patients is monitored to ensure appropriate caloric intake. Caloric needs are lower for wheelchair-bound patients because of their decreased activity, with careful assessment for adequate intake of calcium and vitamin D; supplementation may be required to minimize osteoporosis. Patients are at risk for depression, often resulting in overeating, weight gain, and added burden to their already limited muscle function.

Another common form of MD is myotonic muscular dystrophy, the second most common type of MD in the United States. It is inherited as an autosomal dominant trait. Infants born with this condition may have an inverted V-shaped upper lip, thin cheeks, and wasting of the temporalis muscles. The head is abnormally narrow, and the palate is high and arched. In the ensuing years weakness of the distal muscles leads to progressive challenges in walking. A variety of other findings arise including speech difficulties, gastrointestinal tract problems, endocrinopathies, immunologic deficiencies, cataracts, intellectual impairment, and cardiac involvement.


42.1 The parents of a 3-year-old child are worried about the child’s apparent clumsiness with frequent falls and a waddling gait. The child had normal development of motor skills during the first year of life and has normal language development. Which of the following is consistent with Duchenne muscular dystrophy?

A. Female sex

B. Hypertrophy of the quadriceps

C. 22-year-old sister with Becker muscular dystrophy

D. Gower sign

E. Positive antinuclear antibodies in the blood

42.2 Which of the following is the best screening test for the child discussed in Question 42.1?

A. Muscle biopsy

B. Measurement of serum creatinine

C. Electromyogram

D. Blood analysis for antinuclear antibodies

E. Measurement of serum creatine kinase level

42.3 A 12-year-old healthy boy has noticed some muscle weakness. He has experienced increasing difficulty lifting his backpack and walking long distances. He has no trouble with schoolwork, and he continues to play the piano and video games without tiring. His 38-year-old maternal uncle recently became wheelchair-bound for unclear reasons. Which of the following is the most likely diagnosis?

A. Cerebral palsy

B. Duchenne muscular dystrophy

C. Myasthenia gravis

D. Becker muscular dystrophy

E. Guillain-Barré syndrome

42.4 A 16-year-old has just delivered a newborn through cesarean section; the delivery paperwork states the indication for the cesarean section as “ineffectual uterine contractions.” The newborn has contractures of multiple joints, facial wasting, generalized hypotonia, and weakness. The infant is transferred via helicopter to your facility. In your neonatal intensive care unit the infant’s suck is noted to be weak suggesting that gavage feeds will be required, but the child’s respiratory status worsens resulting in his requiring intubation and ventilator support. Little prenatal history is known until the great grandmother arrives. She reports the mother of the child attends special education classes and walks with braces; she knows little else since the infant’s mother only recently began to live with her. Which of the following is the likely explanation for this child’s condition?

A. Infantile botulism

B. Congenital myotonic dystrophy

C. Duchenne muscular dystrophy

D. Congenital Guillain-Barré syndrome

E. Becker muscular dystrophy


42.1 D. Duchenne muscular dystrophy is an X-linked recessive disease and is clinically evident only in males. Affected boys may have calf hypertrophy that occurs as a compensation for proximal muscle weakness. They will generally develop a Gower sign.

42.2 E. A definitive diagnosis can be made only using muscle biopsy tissue, but serum creatine kinase measurement is preferred because it is less invasive and results can be obtained rapidly. Electromyography will reveal nonspecific myopathy.

42.3 D. This patient does not have muscle weakness that precludes extended use of distal muscles (hands) or limits his manual dexterity. The child’s presentation at age 12 years and a 38-year-old, wheelchair-bound maternal uncle suggest a diagnosis of Becker MD.

42.4 B. A severe, congenital form of myotonic dystrophy can be seen in infants born to mothers with myotonic dystrophy. Those that require ventilation longer than about 30 days have a poorer outcome. For none of the other entities listed would in utero findings be expected.


Image Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder.

Image A Gower sign reflects proximal muscle weakness and is a classic feature of DMD.

Image Creatine kinase level is elevated in patients with DMD and in many female carriers of the gene.


Darras BT. Myopathies. In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA, eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:2241-2244.

DeVivo DC, DiMauro S. Hereditary and acquired types of myopathy. In: McMillan JA, Feigin RD, DeAngelis CD, Jones MD, eds. Oski’s Pediatrics: Principles and Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:2322-2324.

Sarnat HB. Muscular dystrophies. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: WB Saunders; 2011:2119-2129.