present early in life, and progression is then rapid Characteristically there are no facial lines and the eyelids are very weak Winging of the scapulas is seen when the arms are abducted and there is a marked thoracolumbar lordosis Affected muscles include the neck flexors, the serrate and pectoral muscles, biceps and triceps in the upper limbs, the hip flexors, and the anterior tibial muscles; in the late stages, the quadriceps and sartorius in the lower limbs are also affected Retinal vasculopathy is also frequently seen The serum levels of creatine kinase are normal or only mildly elevated The precise molecular mechanism for expression has not been elucidated, but patients are known to have a large deletion involving the q arm of chromosome 4 No gene has been identified in this region; therefore various hypotheses have been presented to explain the mechanism whereby this deletion induces clinical disease.252 Ventricular function is not affected However, supraventricular tachycardia has been reported with a frequency higher than that of the general population.253 Sinus node dysfunction, abnormal AV node or infranodal conduction, and easily inducible atrial fibrillation/flutter have also been reported with an incidence of 27% of the patient population studied.254 Emery-Dreifuss Muscular Dystrophy Emery-Dreifuss muscular dystrophy typically presents between 5 and 15 years of age It can be inherited in an X-linked recessive fashion or in an autosomal dominant or autosomal recessive form The biceps and triceps are more severely affected than the deltoid muscle The peroneals are more involved than the proximal musculature of the legs Contractures generally develop at the elbows, posterior cervical muscles, and the Achilles tendon Pseudohypertrophy is absent Creatine kinase levels are 3 to 10 times above normal Progression is very slow, and the physical limitations are minimal There is normal intellectual function The X-linked form is due to a defect in the gene encoding emerin, a nuclear envelope protein that plays a role in the regulation of many cellular and nucleolar processes However, its role in the pathogenesis of muscle damage has not be elucidated The autosomal dominant form is due to defects in the lamin A/C gene, similar to limb-girdle muscular dystrophy type Ib Again, the role of lamin A/C mutations in the development of the myopathy is not clear The recessive form is also due to defects in the gene encoding lamins A and C.255 How and why defects in the same gene can cause dominant and recessive forms of the disease remains to be discerned Cardiac involvement is often manifest by atrial arrhythmias and atrioventricular block Any degree of atrioventricular block can be present, and a slow junctional escape rhythm is common Severe sinus bradycardia or sinus arrest is seen and may also require pacemaker implantation due to the increased risk of sudden death.256 “Atrial paralysis,” with the absence of P waves and an inability to electrically pace the atrium, is seen Ventricular function is usually normal, but progressive left ventricular dysfunction with fibrous infiltration of the myocardium can be seen,257 and cardiac transplantation has been employed for end-stage disease.258 Patients with bradycardia may have a hypertrophied and dilated left ventricle, probably as a compensatory physiologic response Electrophysiologic studies show prolonged H-V intervals and, on some occasions, a complete absence of the His potential This finding, together with the very slow junctional escape rhythms, suggests that the myopathic process extends into the atrioventricular conduction axis The high risk of sudden death in this variety of muscular dystrophy makes early recognition important, since insertion of a ventricular pacemaker in patients with bradycardia will improve survival Centronuclear Myopathy This uncommon muscular disorder is characterized by ptosis, strabismus, generalized muscle wasting and weakness, and absent or reduced deep tendon reflexes Developmental delay and dysarthria are common A dilated cardiomyopathy has occasionally been observed, and cardiac transplantation has been performed.259 Patients have a prolonged PR interval and a superior axis on the ECG The diagnosis is based on clinical findings, raised levels of creatinekinase in blood, evidence of a myopathy on electromyography, and a typical histologic picture This consists of central location of the nucleus, with variation of muscle fiber diameter and a tendency for predominance of type 1 fibers Inheritance is variable The X-linked form is usually the most severe form and involves the gene encoding myotubularin An autosomal recessive form seems to have a milder course, although patients still present in childhood Finally, the autosomal dominant form is milder, with patients reaching adulthood before the onset of symptoms Nemaline Myopathy The nemaline myopathies are so named because muscle specimens demonstrate rods within the myocytes This group of clinically heterogeneous disorders can result from defects involving actin, troponin, myosin, or tropomyosin Although the skeletal muscles are predominantly involved, cases of hypertrophic and dilated cardiomyopathy are becoming increasingly evident The main focus is on the α-actin gene, ACTA1, in which numerous defects have been described.260 Patients can have a very mild course of skeletal muscle weakness or severe, lethal neonatal disease leading to respiratory failure Hypertrophic cardiomyopathy is more commonly seen,261 but dilated forms of cardiomyopathy have also been reported.262 Friedreich Ataxia Friedreich ataxia is a rare spinocerebellar neuromyelopathy occurring in approximately 1 to 2 per 40,000 The disease is inherited in an autosomal recessive fashion, and most cases are due to homozygosity for an expanded GAA triplet on chromosome 9q13.263 This gene encodes frataxin, a precursor protein that may be involved in the maturation and assembly of iron and sulfur proteins of the mitochondria and cytosol.264 Children present around the age of 6 years The most frequent early symptom is an abnormal gait Neurologic signs include the ataxic gait, absent tendon reflexes, incoordination, and a positive Romberg test.265 Lower limb weakness and muscular atrophy are common, as are dysarthria and loss of vibration and positional sense and extensor plantar responses Some patients have nystagmus The presence of brisk tendon reflexes makes the diagnosis of Friedreich ataxia very unlikely Skeletal involvement is common, with club feet and scoliosis among the most frequent manifestations Apart from the clinical aspects of the disease, nerve conduction studies are essential to support the diagnosis Motor conduction velocity is normal and sensory conduction is absent or markedly reduced Since clinical, ECG, and radiographic examinations of the heart are nonspecific for the evaluation of cardiac involvement in Friedreich ataxia, an echocardiogram is necessary in every patient The heart is involved in a very high percentage of patients, and cardiac symptoms are an integral part of the clinical spectrum of the disease Most usually, the heart exhibits a symmetric, concentric, and slowly progressive