Congenital fiber type disproportion | |
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Other names | Congenital myopathy with fiber type disproportion, CFTD, CFTDM. |
Histopathology of congental muscle fibre dysproportion showing predominance of type 1 fibres which appear to be atrophic (yellow arrows) and few type 2 fibres. ATPase staining (pH 4) of a muscle biopsy. | |
Specialty | Neurology Medical genetics |
Symptoms | contractures, lordosis, scoliosis, hypotonia and weakness, kyphoscoliosis, high-arched palate, dislocated hips, short stature, and feet deformities. [1] |
Complications | Dilated cardiomyopathy [2] |
Causes | Genetic mutations. [2] |
Diagnostic method | Muscle biopsy |
Differential diagnosis | Other types of congenital myopathy. |
Treatment | Symptomatic. |
Congenital fiber type disproportion (CFTD) is an inherited form of myopathy with small type 1 muscle fibers that may occur in a number of neurological disorders. [3] It has a relatively good outcome and follows a stable course. [4] While the exact genetics is unclear, there is an association with mutations in the genes TPM3 , ACTA1 and SELENON . [5] It is a rare condition. [6]
Congenital fiber-type disproportion can cause contractures as well as lordosis or scoliosis. Approximately 30% of people with this disorder have mild to severe respiratory issues due to weakness of breathing muscles. Some people with these breathing issues need noninvasive mechanical ventilation at night and on occasion during the day. Due to throat muscle weakness, approximately 30% of those affected have difficulty swallowing. Dilated cardiomyopathy is a rare complication of this condition. [2]
Other symptoms include congenital nonprogressive hypotonia and weakness, kyphoscoliosis, high-arched palate, dislocated hips, short stature, and feet deformities. [1]
A positive family history has been reported in approximately 40% of cases, however, the inheritance pattern remains unknown. Both autosomal recessive and autosomal dominant inheritance patterns have been proposed. [7] Some CFTD children appear to "grow out" of their hypotonia and weakness during childhood, and this can often be accompanied by a normalization of type 1 fiber size. [3]
According to the current literature, patients are most likely to carry mutations in TPM3, RYR1, ACTA1, and possibly TPM2 and SEPN1 in that order. Nearly every patient with known genetic causes have at least 40% fiber size disproportion. [8] TPM3 mutation is the most prevalent cause of CFTD reported so far. [5]
To be diagnosed with CFTD, the main diagnostic abnormality must be a disproportion in fiber sizes, and the diagnosis is only appropriate after every other type of congenital myopathy has been ruled out. Before CFTD is diagnosed, a number of other neuromuscular (and systemic) disorders must be taken into account and ruled out as possible causes of mild cases of fiber size disproportion (FSD). These factors make CFTD a diagnosis of exclusion. [8]
A consistent difference in size between type 1 fibers, which are small in comparison to type 2 fibers, and type 2 fibers on muscle biopsy is the defining feature of CFTD, but only when it is the primary diagnostic abnormality. [8] The best threshold for the degree of fiber size disproportion required to diagnose CFTD is still being debated, but it is generally agreed that it should be greater than 12%. [5]
Similar to other types of congenital myopathy, there is currently no known treatment that can strengthen muscles or stop the natural progression of muscle weakness. Nonetheless, much can be done to help people with CFTD maintain their health and well-being. [8]
Patients who experience nocturnal hypoventilation in childhood or adulthood nearly always react favorably to noninvasive nocturnal ventilation. [5]
To ensure proper nutrition, some patients with severe dysphagia and generalized weakness need to be fed through a gastrostomy tube. [9]
Patients will occasionally develop severe scoliosis that requires surgical correction, most commonly in connection with mutations in RYR1 and TPM3. [5]
Patients with CFTD may develop contractures of the Achilles tendons as a result of RYR1 and TPM3 mutations; in these cases, surgical tendon lengthening may be necessary. Physiotherapy to maintain ankle and other joint range of motion is frequently beneficial. [8]
Brooke coined the term congenital fiber type disproportion (CFTD) in 1971 to describe children whose biopsies revealed an abnormal size disparity between type 1 and type 2 fibers in the absence of any other obvious histologic abnormalities. [1]
A glycogen storage disease is a metabolic disorder caused by a deficiency of an enzyme or transport protein affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells.
Arthrogryposis (AMC) describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning 'curving of joints'.
Hypotonia is a state of low muscle tone, often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Hypotonia is a lack of resistance to passive movement, whereas muscle weakness results in impaired active movement. Central hypotonia originates from the central nervous system, while peripheral hypotonia is related to problems within the spinal cord, peripheral nerves and/or skeletal muscles. Severe hypotonia in infancy is commonly known as floppy baby syndrome. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child's development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy and/or occupational therapy for remediation.
Nemaline myopathy is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout one's life to some extent. The prevalence is estimated at 1 in 50,000 live births. It is the most common non-dystrophic myopathy.
Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in the center of muscle cells instead of their normal location at the periphery.
Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place.
Emery–Dreifuss muscular dystrophy (EDMD) is a type of muscular dystrophy, a group of heritable diseases that cause progressive impairment of muscles. EDMD affects muscles used for movement, causing atrophy, weakness and contractures. It almost always affects the heart, causing abnormal rhythms, heart failure, or sudden cardiac death. It is rare, affecting 0.39 per 100,000 people. It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.
Congenital myopathy is a very broad term for any muscle disorder present at birth. This defect primarily affects skeletal muscle fibres and causes muscular weakness and/or hypotonia. Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year. As a whole, congenital myopathies can be broadly classified as follows:
Bethlem myopathy is predominantly an autosomal dominant myopathy, classified as a congenital form of limb-girdle muscular dystrophy. There are two types of Bethlem myopathy, based on which type of collagen is affected.
Central core disease (CCD), also known as central core myopathy, is an autosomal dominant inherited muscle disorder present from birth that negatively affects the skeletal muscles. It was first described by Shy and Magee in 1956. It is characterized by the appearance of the myofibril under the microscope.
Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation.
Marden–Walker syndrome (MWS) is a rare autosomal recessive congenital disorder. It is characterized by blepharophimosis, microcephaly, micrognathia, multiple joint contractures, arachnodactyly, camptodactyly, kyphoscoliosis and delayed motor development and is often associated with cystic dysplastic kidneys, dextrocardia, Dandy–Walker malformation and agenesis of corpus callosum.
Ullrich congenital muscular dystrophy (UCMD) is a form of congenital muscular dystrophy. There are two forms: UCMD1 and UCMD2.
Collagen VI (ColVI) is a type of collagen primarily associated with the extracellular matrix of skeletal muscle. ColVI maintains regularity in muscle function and stabilizes the cell membrane. It is synthesized by a complex, multistep pathway that leads to the formation of a unique network of linked microfilaments located in the extracellular matrix (ECM). ColVI plays a vital role in numerous cell types, including chondrocytes, neurons, myocytes, fibroblasts, and cardiomyocytes. ColVI molecules are made up of three alpha chains: α1(VI), α2(VI), and α3(VI). It is encoded by 6 genes: COL6A1, COL6A2, COL6A3, COL6A4, COL6A5, and COL6A6. The chain lengths of α1(VI) and α2(VI) are about 1,000 amino acids. The chain length of α3(VI) is roughly a third larger than those of α1(VI) and α2(VI), and it consists of several spliced variants within the range of 2,500 to 3,100 amino acids.
Multi/minicore myopathy is a congenital myopathy usually caused by mutations in either the SELENON and RYR1 genes. It is characterised the presence of multifocal, well-circumscribed areas with reduction of oxidative staining and low myofibrillar ATPase on muscle biopsy. It is also known as Minicore myopathy, Multicore myopathy, Multiminicore myopathy, Minicore myopathy with external ophthalmoplegia, Multicore myopathy with external ophthalmoplegia and Multiminicore disease with external ophthalmoplegia.
Congenital distal spinal muscular atrophy (cDSMA), also known as distal hereditary motor neuropathytype VIII (dHMN8), is a hereditary medical condition characterized by muscle wasting (atrophy), particularly of distal muscles in legs and hands, and by early-onset contractures of the hip, knee, and ankle. Affected individuals often have shorter lower limbs relative to the trunk and upper limbs. The condition is a result of a loss of anterior horn cells localized to lumbar and cervical regions of the spinal cord early in infancy, which in turn is caused by a mutation of the TRPV4 gene. The disorder is inherited in an autosomal dominant manner. Arm muscle and function, as well as cardiac and respiratory functions are typically well preserved.
Muscle–eye–brain (MEB) disease, also known as muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3 (MDDGA3), is a kind of rare congenital muscular dystrophy (CMD), largely characterized by hypotonia at birth. Patients have muscular dystrophy, central nervous system abnormalities and ocular abnormalities. The condition is degenerative.
Calpainopathy is the most common type of autosomal recessive limb-girdle muscular dystrophy (LGMD). It preferentially affects the muscles of the hip girdle and shoulder girdle.
Rigid spine syndrome, also known as congenital muscular dystrophy with rigidity of the spine (CMARS), is a rare and often debilitating neuromuscular disorder. It is characterized by progressive muscle stiffness and rigidity, particularly in the spine, which can severely limit mobility and impact quality of life. This condition is typically present from birth or early childhood and tends to worsen over time.
LAMA2 muscular dystrophy (LAMA2-MD) is a genetically determined muscle disease caused by pathogenic mutations in the LAMA2 gene. It is a subtype of a larger group of genetic muscle diseases known collectively as congenital muscular dystrophies. The clinical presentation of LAMA2-MD varies according to the age at presentation. The severe forms present at birth and are known as early onset LAMA2 congenital muscular dystrophy type 1A or MDC1A. The mild forms are known as late onset LAMA2 muscular dystrophy or late onset LAMA2-MD. The nomenclature LGMDR23 can be used interchangeably with late onset LAMA2-MD.