Fukuyama congenital muscular dystrophy

Last updated
Fukuyama congenital muscular dystrophy
Other namesCongenital muscular dystrophy, Fukuyama type [1]
Autosomal recessive - en.svg
Fukuyama congenital muscular dystrophy has an autosomal recessive pattern of inheritance
Symptoms Seizures [2]
CausesFKTN gene mutation [3]
Diagnostic method Serum creatine kinase concentration and muscle biopsies [2] [4]
TreatmentPhysical therapy [1]

Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal recessive form of muscular dystrophy (weakness and breakdown of muscular tissue) mainly described in Japan but also identified in Turkish and Ashkenazi Jewish patients; [5] fifteen cases were first described on 1960 by Dr. Yukio Fukuyama. [6]

Contents

FCMD mainly affects the brain, eyes, and muscles, in particular, the disorder affects development of the skeletal muscles leading to weakness and deformed appearances, and brain development is blunted affecting cognitive functioning as well as social skills. [1] [3] In 1995, the disorder was linked to mutations in a gene coding for the protein fukutin (the FCMD gene). Fukuyama congenital muscular dystrophy is the second most prevalent form of muscular dystrophy in Japan. One out of every 90 people in Japan is a heterozygous carrier.[ medical citation needed ]

Symptoms and signs

In terms of the signs/symptoms of Fukuyama congenital muscular dystrophy it is characterized by a decrease in skeletal muscle tone as well as an impairment in brain and eye development. Initial symptoms of FCMD present in early infancy as decreased ability to feed. Marked differences in facial appearance occur due to decreased muscle tone. Further characteristics include: [2]

Fukuyama congenital muscular dystrophy also affects the nervous system and various associated parts. FCMD affects normal development of the brain producing a broadly smooth, bumpy shaped cortex named cobblestone lissencephaly as well as various other malformations, notably micropolygyria. Children also experience delayed myelination in the brain. [7]

Cause

CHR 9 Human male karyotpe high resolution - Chromosome 9 cropped.png
CHR 9

The cause of Fukuyama congenital muscular dystrophy is rooted in the FKTN gene, located at human chromosome 9q31, encoding the protein fukutin. Mutations in this gene, and therefore the fukutin protein, are the cause of FCMD. [8] The disease is inherited in an autosomal recessive manner. [5]

This means the defective gene responsible for the disorder is located on an autosome (chromosome 9 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene but usually do not experience any signs or symptoms of the disorder. [9]

Two mutations have been identified. The first and most common is an SVA retrotransposal insertion in the 3'-untranslated region. The second is a deep-intronic point mutation c.647+2084G>T. This second mutation has only been found to date in the presence of the first mutation. [10]

Pathophysiology

Protein DAG1 Protein DAG1 PDB 1u2c.png
Protein DAG1

The mechanism of this sub-type of muscular dystrophy consists of a mutation in the FKTN gene which results in a malformed fukutin protein. It is thought that fukutin modifies the alpha-dystroglycan protein, which is important in anchoring cells to certain molecules, specifically including some proteins. Alpha-dystroglycan in skeletal muscles helps to prevent the breakdown of muscle fibers through stabilization and protection. Alpha-dystroglycan also helps brain development by assisting in the migration of neurons. Most frequently, FKTN is mutated in such a way that creates a shortage of fukutin in the cell, which in turn creates problems during formation of alpha-dystroglycan leading to less stabilization of muscle cells. [5] [2] Use of the destabilized muscle fibers over time causes them to break down and a gradual decline in muscle tone and atrophy of muscle fibers occurs. The decline in cerebral fukutin causes neuronal cells to continue moving beyond their intended destination. Additionally, oxidative stress has some effect on astrocytes (as well as, neurons) when fukutin is subdued. [11] [12]

Diagnosis

In terms of diagnosis of Fukuyama congenital muscular dystrophy, serum creatine kinase concentration and muscle biopsies can be obtained to help determine if the individual has FMCD. FKTN molecular genetic testing is used to determine a mutation in the FKTN gene after a serum creatine kinase concentration, muscle biopsies, and/or MRI imaging have presented abnormalities indicative of FCMD, the presence of the symptoms indicates Fukuyama congenital muscular dystrophy. The available genetic test include: [2] [4]

Gene structure.svg

Treatment

Currently this sub-type of muscular dystrophy has no cure and no definitive treatment exists. [13] Treatment offers preventative tactics to delay muscle breakdown and increase life expectancy. Stretching and physical therapy can increase mobility. Treatment also includes correcting skeletal abnormalities through orthopedic surgery and other orthopedic techniques. Antiepileptic medication is administered to help prevent seizures. ACE inhibitors and beta blockers help treat heart conditions, and respiratory assistance is more than likely needed at some point for the affected individual. [2] [13] [14]

Prognosis

Fukuyama congenital muscular dystrophy has a poor prognosis. Most children with FCMD reach a maximum mobility at sitting upright and sliding. Due to the compounded effects of continually worsening heart problems, impaired mental development, problems swallowing and additional complications, children with FCMD rarely live through adolescence, the disorder proves fatal by age 20. [2] [15]

See also

Related Research Articles

<span class="mw-page-title-main">Muscular dystrophy</span> Genetic disorder

Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Some types are also associated with problems in other organs.

<span class="mw-page-title-main">Limb–girdle muscular dystrophy</span> Medical condition

Limb–girdle muscular dystrophy (LGMD) is a genetically heterogeneous group of rare muscular dystrophies that share a set of clinical characteristics. It is characterised by progressive muscle wasting which affects predominantly hip and shoulder muscles. LGMD usually has an autosomal pattern of inheritance. It currently has no known cure or treatment.

Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.

<span class="mw-page-title-main">Walker–Warburg syndrome</span> Medical condition

Walker–Warburg syndrome (WWS), also called Warburg syndrome, Chemke syndrome, HARD syndrome, Pagon syndrome, cerebroocular dysgenesis (COD) or cerebroocular dysplasia-muscular dystrophy syndrome (COD-MD), is a rare form of autosomal recessive congenital muscular dystrophy. It is associated with brain and eye abnormalities. This condition has a worldwide distribution. Walker-Warburg syndrome is estimated to affect 1 in 60,500 newborns worldwide.

<span class="mw-page-title-main">Autosomal recessive multiple epiphyseal dysplasia</span> Medical condition

Autosomal recessive multiple epiphyseal dysplasia (ARMED), also called epiphyseal dysplasia, multiple, 4 (EDM4), multiple epiphyseal dysplasia with clubfoot or –with bilayered patellae, is an autosomal recessive congenital disorder affecting cartilage and bone development. The disorder has relatively mild signs and symptoms, including joint pain, scoliosis, and malformations of the hands, feet, and knees.

<span class="mw-page-title-main">Congenital muscular dystrophy</span> Medical condition

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.

<span class="mw-page-title-main">Emery–Dreifuss muscular dystrophy</span> Medical condition

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:

<span class="mw-page-title-main">Laminopathy</span> Medical condition

Laminopathies are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. They are included in the more generic term nuclear envelopathies that was coined in 2000 for diseases associated with defects of the nuclear envelope. Since the first reports of laminopathies in the late 1990s, increased research efforts have started to uncover the vital role of nuclear envelope proteins in cell and tissue integrity in animals.

<span class="mw-page-title-main">Fukutin</span> Mammalian protein found in Homo sapiens

Fukutin is a eukaryotic protein necessary for the maintenance of muscle integrity, cortical histogenesis, and normal ocular development. Mutations in the fukutin gene have been shown to result in Fukuyama congenital muscular dystrophy (FCMD) characterised by brain malformation - one of the most common autosomal-recessive disorders in Japan. In humans this protein is encoded by the FCMD gene, located on chromosome 9q31. Human fukutin exhibits a length of 461 amino acids and a predicted molecular mass of 53.7 kDa.

<span class="mw-page-title-main">Fukutin-related protein</span> Mammalian protein found in Homo sapiens

Fukutin-related protein (FKRP) is also known as FKRP_HUMAN, LGMD2I, MDC1C, MDDGA5, MDDGB5, and MDDGC5. FKRP can be located in the brain, cardiac muscle and skeletal muscle, and in cells it is found in the Golgi apparatus. Fukutin is expressed in the mammalian retina and is located in the Golgi complex of retinal neurons.

Micropolygyria is a neuronal migration disorder, a developmental anomaly of the brain characterized by development of numerous small convolutions (microgyri), causing intellectual disability and/or other neurological disorders. It is present in a number of specific neurological diseases, notably multiple sclerosis and Fukuyama congenital muscular dystrophy, a specific disease cause by mutation in the Fukutin gene (FKTN).

<span class="mw-page-title-main">SGCB</span> Protein-coding gene in the species Homo sapiens

Beta-sarcoglycan is a protein that in humans is encoded by the SGCB gene.

<span class="mw-page-title-main">SGCA</span> Protein-coding gene in the species Homo sapiens

Alpha-sarcoglycan is a protein that in humans is encoded by the SGCA gene.

<span class="mw-page-title-main">Pikachurin</span> Protein-coding gene in the species Homo sapiens

Pikachurin, also known as AGRINL (AGRINL) and EGF-like, fibronectin type-III and laminin G-like domain-containing protein (EGFLAM), is a protein that in humans is encoded by the EGFLAM gene.

<span class="mw-page-title-main">Ullrich congenital muscular dystrophy</span> Medical condition

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.

<span class="mw-page-title-main">LMNA-related congenital muscular dystrophy</span> Medical condition

Lamin A/C congenital muscular dystrophy (CMD) is a disease that it is included in laminopathies. Laminopathies are caused, among other mutations, to mutations in LMNA, a gene that synthesizes lamins A and C.

<span class="mw-page-title-main">Muscle–eye–brain disease</span> Medical condition

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.

<span class="mw-page-title-main">Calpainopathy</span> Medical condition

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.

References

  1. 1 2 3 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Congenital muscular dystrophy, Fukuyama type". www.orpha.net. Retrieved 2016-05-11.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. 1 2 3 4 5 6 7 Saito, Kayoko (1993). "Fukuyama Congenital Muscular Dystrophy". Fukuyama Congenital Muscular Dystropy. National Center for Biotechnology Information. PMID   20301385 . Retrieved 30 November 2012.{{cite book}}: |work= ignored (help)
  3. 1 2 "Fukuyama congenital muscular dystrophy". Genetics Home Reference. Retrieved 2012-11-26.
  4. 1 2 "Fukuyama congenital muscular dystrophy - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-24.
  5. 1 2 3 Online Mendelian Inheritance in Man (OMIM): 253800
  6. ↑ Fukuyama Y; Kawazura M; Haruna, H (1960). "A peculiar form of congenital progressive muscular dystrophy". Paediat. Univ. Tokyo. 4: 5–8.
  7. ↑ Rutherford, Mary (2012). MRI of the Neonatal Brain. ISBN   978-0-7020-2534-1.Chapter 14
  8. ↑ Online Mendelian Inheritance in Man (OMIM): 607440
  9. ↑ "Autosomal recessive: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2016-05-24.
  10. ↑ Kobayashi K, Kato R, Kondo-Iida E, Taniguchi-Ikeda M, Osawa M, Saito K, Toda T (2017) Deep-intronic variant of fukutin is the most prevalent point mutation of Fukuyama congenital muscular dystrophy in Japan. J Hum Genet doi: 10.1038/jhg.2017.71
  11. ↑ Yamamoto, T; Kato, Y; Kawaguchi-Niida, M; Shibata, N; Osawa, M; Saito, K; Kröger, S; Kobayashi, M (2008-07-01). "Characteristics of neurons and glia in the brain of Fukuyama type congenital muscular dystrophy". Acta Myologica. 27 (1): 9–13. ISSN   1128-2460. PMC   2859607 . PMID   19108571.
  12. ↑ Saito, Fumiaki; Matsumura, Kiichiro (2011-01-01). "Fukuyama-type congenital muscular dystrophy and defective glycosylation of α-dystroglycan". Skeletal Muscle. 1: 22. doi: 10.1186/2044-5040-1-22 . ISSN   2044-5040. PMC   3156645 .
  13. 1 2 Lopate, Glenn. "Congenital Muscular Dystrophy Treatment & Management". Medscape. Retrieved 30 November 2012.
  14. ↑ Sato, Takatoshi; Murakami, Terumi; Ishiguro, Kumiko; Shichiji, Minobu; Saito, Kayoko; Osawa, Makiko; Nagata, Satoru; Ishigaki, Keiko (2016-03-01). "Respiratory management of patients with Fukuyama congenital muscular dystrophy". Brain & Development. 38 (3): 324–330. doi:10.1016/j.braindev.2015.08.010. ISSN   1872-7131. PMID   26363734. S2CID   206315560. – via ScienceDirect  (Subscription may be required or content may be available in libraries.)
  15. ↑ Lynn, D. Joanne; Newton, Herbert B.; Rae-Grant, Alexander (2004-01-01). The 5-minute Neurology Consult. Lippincott Williams & Wilkins. p. 283. ISBN   9780683307238.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.