Congenital myopathies

Dorn Spinal Therapy

Spine Healing Therapy

Get Instant Access

Genetic testing

NCV/EMG

Laboratory

Imaging

Biopsy

+

++

+

+

+++

Fingerprint Body MyopathieNemaline Rod Electron Microscopy

Fig. 20. Nemaline myopathy. A Large nemalin rod inclusions (arrows) on Trichrome stain. B Electron microscopy-nemalin rod inclusion (arrows)

Fig. 19. Nemaline myopathy. A Distal leg atrophy in a patient with nemaline myopathy. B Atrophy of the proximal arm muscles, neck muscles, and weakness of the facial muscles. C Bilateral hand wasting

Fig. 20. Nemaline myopathy. A Large nemalin rod inclusions (arrows) on Trichrome stain. B Electron microscopy-nemalin rod inclusion (arrows)

Central Core Disease Baby
Fig. 21. Central Core Disease. A Central cores with trichrome and eosin staining (arrows). B Multicore disease - multiple cores (arrows) on NADH-trichrome stain

Fig. 22. Congenital fiber disproportion showing numerous smaller type 1 fibers (arrows), and normal fibers (arrow heads)

Fig. 23. Centronuclear Myopathy. A Adult onset subject with red stained central nuclei (arrows) seen in small type 1 fibers (arrow head). B NADH tetrazo-lium reductase showing small type 1 fibers (arrows), and central nuclei with mitochondria arranged like spokes in a wheel (arrow heads)

Fig. 22. Congenital fiber disproportion showing numerous smaller type 1 fibers (arrows), and normal fibers (arrow heads)

Fig. 23. Centronuclear Myopathy. A Adult onset subject with red stained central nuclei (arrows) seen in small type 1 fibers (arrow head). B NADH tetrazo-lium reductase showing small type 1 fibers (arrows), and central nuclei with mitochondria arranged like spokes in a wheel (arrow heads)

Spokes Wheel Nuclei Nadh

Distribution/anatomy

Time course

Onset/age

Central core disease (CCD) - generalized or limited to upper or lower limbs. In multi or minicore disease (MCD), nemalin myopathy (NM), and centronuclear myopathy (CNM) all muscle types including the face may be affected. Congenital fiber type disproportion (CFD) may affect any muscle mass, subjects often have a thin face and body. In Fingerprint body myopathy (FPM) proximal muscles are more severely affected than distal. Limb and trunk muscles may also be affected. In Bethlem myopathy (BM) proximal muscles, and extensors more than flexors are affected.

Variable. In CCD progression is slow, whereas patients with MCD may have a benign disorder with static muscle weakness or with some improvement over time. In MCD spinal rigidity becomes a significant feature restricting head mobility. In NM the progression of the disease is variable depending on the type. In CNM, the progression is more severe in the infantile form, and milder in later onset forms. Childhood and adult onset CFD develops insidiously, whereas neonatal disease progresses more rapidly. In CFD, FPM, and BM the myopathy is non-progressive and may even improve clinically as the child grows. Severely involved infants with CFD may die from respiratory failure.

In CCD 20% of patients present between 0 and 5 years, 30% between 6 and 20 years, 30% between 21 and 40 years, 15% over 40 years. MCD usually presents in the first year of life, however, approximately 10% of cases present in adulthood. CFD and CNM may present at any age. FPM usually begins in childhood. BM may start in childhood to the second decade.

Clinical syndrome

Consists of a variety of syndromes including 1) Central core disease 2) Multi or minicore disease 3) Nemalin myopathy (Fig. 19) 4) Centronuclear myopathy 5) Congenital fiber type disproportion 6) Fingerprint body myopathy 7) Bethlem myopathy

- CCD. Presents with slowly progressive muscle weakness. There is generalized weakness in 40% of patients, or the disease may be limited to the upper or lower limbs. Rarely the face is involved, and strength may be normal in 15% of cases. Muscle atrophy occurs in 50% and reflexes are decreased in 45% of subjects. Other associations are kyphoscoliosis or lordosis, foot deformities, congenital hip dislocations, contractures, hypertrophic cardiomyopathy, and arrythmias. There is also an association between central core disease and ryanodine receptor gene abnormalities associated with malignant hyperthermia (MH).

- MCD. The infant presents with hypotonia and delayed motor development. They may also have evidence of cleft palate, dislocated hip, or arthrogryposis. Patients may have hypotonia in infancy, although the paraspinal muscles may be rigid and the neck relatively immobile. Minimal proximal and distal weakness may be observed in several muscles. The facial muscles are not involved. The deep tendon reflexes are reduced. Despite hypotonia, patients may have a rigid spine and kyphoscoliosis that may progress in late childhood. The disease may be misdiagnosed as SMA. Approximately 20% of patients have ophthalmoplegia.

- NM. There are several types including congenital forms that vary in severity. The disorder can be characterized as follows: 1) severe congenital 2) intermediate congenital 3) typical congenital 4) juvenile 5) other. The infantile form is rapidly fatal. Infants present with severe hypotonia and facial diplegia, and may develop failure to thrive secondary to inability to suck and respiratory complications. Affected subjects are extremely hypotonic with depressed deep tendon reflexes and proximal weakness. The degree of weakness is variable. Bulbar muscles may be affected resulting in hypernasal speech. Ophthalmoplegia may occur. Patients are thin due to reduced muscle bulk and facial weakness results in loss of facial expression. Weakness of intercostal and diaphragm muscles may causes respiratory impairment. The adult form may only present with weakness in the seventh decade. The course of nemaline myopathy may be static or progressive. Most patients have progressive weakness, although occasionally weakness improves over time.

- CNM. In the infantile form, often referred to as myotubular myopathy, affected subjects may have a large head, with a narrow face, and long digits. Subjects often develop severe hypotonia, weakness of proximal and distal muscles, ophthalmoplegia and ptosis. They may also develop severe hypotonia, proximal and distal muscle weakness, respiratory insufficiency, ophthalmoplegia and ptosis. Subjects may become respirator dependent. Older patients with CNM develop weakness of proximal and distal muscles coupled with kyphoscoliosis, pes equinovarus, leg cramps, ophthalmoplegia, facial, and scapular weakness.

- CFD. There is prominant facial weakness with ptosis, variable external ophthalmoplegia, and pharyngeal muscles weakness. The tongue is thin but no fasciculations are seen. Patients are often very thin with reduced muscle mass. Tendon reflexes are often reduced. Congenital contractures, scoliosis, and foot deformities are present in a minority. Cardiomyopathy is rare in CFD.

- FPM. There is symmetric weakness of proximal greater than distal muscles, and limb and trunk. Cranial nerves are usually spared. Patients occasionally have intellectual impairment.

- BM. Congenital flexion contractures of the ankles, elbows, interphalangeal joints of the fingers are typical, although the neck and back are usually not involved. Many patients also have hypotonia and torticollis.

Pathogenesis - CCD. There is an autosomal dominant abnormality of the ryanodine recep tor localized to chromosome 19q13.1. At least 22 mutations have been described in CCD.

- MCD. Most patients have a sporadic disease. Minicores are small lesions of sarcomere disruption with Z band streaming and dissolution of myofilaments.

- NM. Five gene loci have been identified: slow alpha-tropomyosin (TPM3 on chromosome 1q) for autosomal dominant or autosomal recessive NM, nebulin (NEB on 2q) for autosomal recessive NM, alpha-actin (ACTA1 on chromosome 1q) with both recessive and dominant mutations, troponin T1 (TNNT1 on chromosome 19q) causing autosomal recessive NM, and beta tropomyosin (TPM2 on chromosome 9p) in several autosomal dominant cases.

- CFD. Most cases are sporadic, with some families having an autosomal dominant or recessive inheritance.

- CNM. The gene responsible for most cases is unknown. In some cases there appears to be an autosomal dominant inheritance, in others autosomal recessive. Some patients may have a mutation of the MYF6 gene mutation (Ala112Ser) on chromosome 12q21. The severe infantile form of CNM, X-linked myotubular myopathy, may be due to any one of over 100 mutations of the gene MTM1 on Xq28 coding for myotubularin.

- FPM. Unknown, may be sporadic or autosomal recessive.

- BM. Autosomal dominant disorder characterized by missense or splice-site mutation of one of the 3 collagen VI genes (a1, a2, a3 - COL6A1-3). COL6A1 and 2 are localized on chromosome 21q22.3 and COL6A3 on 2q37. At least 6 mutations have been described. Collagen VI is important in stabilizing the myofiber basal lamina.

Was this article helpful?

0 0
The Basics Of Body Building

The Basics Of Body Building

Bodybuilding is the process of developing muscle fibers through various techniques. It is achieved through muscle conditioning, weight training, increased calorie intake, and resting your body as it repairs and heals itself, before restarting your workout routine.

Get My Free Ebook


Post a comment