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Fukuyama congenital muscular dystrophy(MDDGA4)

MedGen UID:
140820
Concept ID:
C0410174
Disease or Syndrome
Synonyms: Cerebromuscular dystrophy, Fukuyama type; Fukuyama CMD; Fukuyama muscular dystrophy; Fukuyama syndrome; Fukuyama type muscular dystrophy; MDDGA4; Muscular dystrophy, congenital progressive, with mental retardation; Muscular dystrophy, congenital, Fukuyama type; Muscular dystrophy, congenital, with central nervous system involvement; Polymicrogyria with muscular dystrophy; WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, FKTN-RELATED
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Fukuyama muscular dystrophy (111502003); Fukuyama congenital muscular dystrophy (111502003)
 
Gene: FKTN
Cytogenetic location: 9q31.2
OMIM®: 253800
Orphanet: ORPHA272

Disease characteristics

Excerpted from the GeneReview: Fukuyama Congenital Muscular Dystrophy
Fukuyama congenital muscular dystrophy (FCMD) is characterized by hypotonia, symmetric generalized muscle weakness, and CNS migration disturbances that result in changes consistent with cobblestone (previously type II) lissencephaly with cerebral and cerebellar cortical dysplasia. Mild, typical, and severe phenotypes are recognized. Onset typically occurs in early infancy, with a poor suck, weak cry, and floppiness. Affected individuals have contractures of the hips, knees, and interphalangeal joints. Later features include myopathic facial appearance, pseudohypertrophy of the calves and forearms, motor and speech retardation, intellectual disability, seizures, ophthalmologic abnormalities including visual impairment and retinal dysplasia, and progressive cardiac involvement in individuals older than age ten years. Swallowing disturbance occurs in individuals with severe FCMD and in individuals older than age ten years, leading to recurrent aspiration pneumonia and death. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Kayoko Saito   view full author information

Additional descriptions

From OMIM
MDDGA4 is a severe autosomal recessive muscular dystrophy-dystroglycanopathy with characteristic brain and eye malformations, seizures, and mental retardation. Cardiac involvement in FCMD/MEB occurs in the second decade of life in those who survive. FKTN-related Walker-Warburg syndrome is a more severe manifestation of the disorder, with death usually in the first year of life. These entities are part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007; Muntoni and Voit, 2004; Muntoni et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).  http://www.omim.org/entry/253800
From GHR
Fukuyama congenital muscular dystrophy is an inherited condition that predominantly affects the muscles, brain, and eyes. Congenital muscular dystrophies are a group of genetic conditions that cause muscle weakness and wasting (atrophy) beginning very early in life. Fukuyama congenital muscular dystrophy affects the skeletal muscles, which are muscles the body uses for movement. The first signs of the disorder appear in early infancy and include a weak cry, poor feeding, and weak muscle tone (hypotonia). Weakness of the facial muscles often leads to a distinctive facial appearance including droopy eyelids (ptosis) and an open mouth. In childhood, muscle weakness and joint deformities (contractures) restrict movement and interfere with the development of motor skills such as sitting, standing, and walking. Fukuyama congenital muscular dystrophy also impairs brain development. People with this condition have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain develops a bumpy, irregular appearance (like that of cobblestones). These changes in the structure of the brain lead to significantly delayed development of speech and motor skills and moderate to severe intellectual disability. Social skills are less severely impaired. Most children with Fukuyama congenital muscular dystrophy are never able to stand or walk, although some can sit without support and slide across the floor in a seated position. More than half of all affected children also experience seizures. Other signs and symptoms of Fukuyama congenital muscular dystrophy include impaired vision, other eye abnormalities, and slowly progressive heart problems after age 10. As the disease progresses, affected people may develop swallowing difficulties that can lead to a bacterial lung infection called aspiration pneumonia. Because of the serious medical problems associated with Fukuyama congenital muscular dystrophy, most people with the disorder live only into late childhood or adolescence.  http://ghr.nlm.nih.gov/condition/fukuyama-congenital-muscular-dystrophy

Clinical features

Microphthalmos
MedGen UID:
504501
Concept ID:
CN000533
Finding
A developmental anomaly characterized by abnormal smallness of one or both eyes.
Encephalocele
MedGen UID:
505091
Concept ID:
CN001885
Finding
A neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
Strabismus is the intermittent or constant misalignment of an eye so that its line of vision is not pointed at the same object as the other eye. Strabismus is caused by an imbalance in the extraocular muscles which control the positioning of the eyes. Strabismus is normal in newborns but should resolve by the time the baby is 6 months old. In older children with strabismus, the brain may learn to ignore the input from one eye, and this may lead to amblyopia, a potentially permanent decrease in vision in that eye if not corrected.
Cataract
MedGen UID:
368085
Concept ID:
C1962983
Finding
Retinal detachment
MedGen UID:
368440
Concept ID:
C1963229
Finding
Retinal dysplasia
MedGen UID:
372635
Concept ID:
C1970771
Finding
Hypermetropia
MedGen UID:
504484
Concept ID:
CN000506
Finding
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Myopia
MedGen UID:
504487
Concept ID:
CN000511
Finding
An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry.
Microphthalmos
MedGen UID:
504501
Concept ID:
CN000533
Finding
A developmental anomaly characterized by abnormal smallness of one or both eyes.
Optic atrophy
MedGen UID:
504537
Concept ID:
CN000609
Finding
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Agenesis of corpus callosum
MedGen UID:
373288
Concept ID:
C1837248
Finding
Intellectual disability
MedGen UID:
334384
Concept ID:
C1843367
Finding
Hypoplasia of the brainstem
MedGen UID:
337795
Concept ID:
C1847358
Finding
Cerebellar cyst
MedGen UID:
339835
Concept ID:
C1847762
Finding
Hypoplasia of the pyramidal tract
MedGen UID:
342610
Concept ID:
C1850871
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Hydrocephalus
MedGen UID:
369747
Concept ID:
C1963137
Finding
Pachygyria
MedGen UID:
504794
Concept ID:
CN001193
Finding
A congenital abnormality of the cerebral hemisphere chacterized by unusually thick gyrations (convolutions) of the cerebral cortex.
Cerebellar hypoplasia
MedGen UID:
504799
Concept ID:
CN001210
Finding
Underdevelopment of the cerebellum.
Holoprosencephaly
MedGen UID:
504813
Concept ID:
CN001246
Finding
Holoprosencephaly is a structural anomaly of the brain in which the developing forebrain fails to divide into two separate hemispheres and ventricles.
Encephalocele
MedGen UID:
505091
Concept ID:
CN001885
Finding
A neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull.
Polymicrogyria
MedGen UID:
505116
Concept ID:
CN001926
Finding
A congenital abnormality of the cerebral hemisphere characterized by an excessive number of small gyri (convolutions) on the surface of the brain.
Exaggerated startle response
MedGen UID:
505176
Concept ID:
CN002058
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Type II lissencephaly
MedGen UID:
506044
Concept ID:
CN006349
Finding
A form of lissencephaly characterized by an uneven cortical surface with a so called 'cobblestone' appearace. There are no distinguishable cortical layers.
Spinal rigidity
MedGen UID:
346721
Concept ID:
C1858025
Finding
Encephalocele
MedGen UID:
505091
Concept ID:
CN001885
Finding
A neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull.
Scoliosis
MedGen UID:
427922
Concept ID:
CN002409
Finding
The presence of an abnormal lateral curvature of the spine.
Defect in the atrial septum
MedGen UID:
504879
Concept ID:
CN001485
Finding
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Pulmonic stenosis
MedGen UID:
504885
Concept ID:
CN001495
Finding
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis) or just below the pulmonary valve (infundibular stenosis).
Transposition of the great arteries
MedGen UID:
504901
Concept ID:
CN001518
Finding
A complex congenital heart defect in which the aorta arises from the morphologic right ventricle and the pulmonary artery arises from the morphologic left ventricle.
Myocardial fibrosis
MedGen UID:
504911
Concept ID:
CN001534
Finding
Elevated serum creatine phosphokinase
MedGen UID:
505493
Concept ID:
CN002923
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase, CPK; EC 2.7.3.2) in the blood. CPK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Respiratory insufficiency
MedGen UID:
155440
Concept ID:
C0748358
Finding
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)
Calf muscle hypertrophy
MedGen UID:
330870
Concept ID:
C1842554
Finding
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Skeletal muscle atrophy
MedGen UID:
505481
Concept ID:
CN002890
Finding
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Congenital muscular dystrophy
MedGen UID:
505584
Concept ID:
CN003380
Finding
Calf muscle hypertrophy
MedGen UID:
330870
Concept ID:
C1842554
Finding

Professional guidelines

PubMed

Wang CH, Bonnemann CG, Rutkowski A, Sejersen T, Bellini J, Battista V, Florence JM, Schara U, Schuler PM, Wahbi K, Aloysius A, Bash RO, Béroud C, Bertini E, Bushby K, Cohn RD, Connolly AM, Deconinck N, Desguerre I, Eagle M, Estournet-Mathiaud B, Ferreiro A, Fujak A, Goemans N, Iannaccone ST, Jouinot P, Main M, Melacini P, Mueller-Felber W, Muntoni F, Nelson LL, Rahbek J, Quijano-Roy S, Sewry C, Storhaug K, Simonds A, Tseng B, Vajsar J, Vianello A, Zeller R; International Standard of Care Committee for Congenital Muscular Dystrophy
J Child Neurol 2010 Dec;25(12):1559-81. Epub 2010 Nov 15 doi: 10.1177/0883073810381924. [Epub ahead of print] PMID: 21078917

Recent clinical studies

Etiology

Murakami T, Ishigaki K, Shirakawa S, Ikenaka H, Sakauchi M, Osawa M
Brain Dev 2012 Apr;34(4):293-7. Epub 2011 Jul 2 doi: 10.1016/j.braindev.2011.06.002. [Epub ahead of print] PMID: 21726969
Xiong H, Wang S, Kobayashi K, Jiang Y, Wang J, Chang X, Yuan Y, Liu J, Toda T, Fukuyama Y, Wu X
Am J Med Genet A 2009 Nov;149A(11):2403-8. doi: 10.1002/ajmg.a.33057. PMID: 19842201
Wakayama Y, Inoue M, Kojima H, Yamashita S, Shibuya S, Jimi T, Hara H, Matsuzaki Y, Oniki H, Kanagawa M, Kobayashi K, Toda T
Histol Histopathol 2008 Dec;23(12):1425-38. PMID: 18830929
Saito K
Prenat Diagn 2006 May;26(5):415-7. doi: 10.1002/pd.1426. PMID: 16570239
Stern LM, Albertyn L, Manson JI
Dev Med Child Neurol 1990 Sep;32(9):808-13. PMID: 2227144

Diagnosis

Costa C, Oliveira J, Gonçalves A, Santos R, Bronze-da-Rocha E, Rebelo O, Pais RP, Fineza I
Neuromuscul Disord 2013 Jul;23(7):557-61. Epub 2013 Apr 11 doi: 10.1016/j.nmd.2013.03.005. [Epub ahead of print] PMID: 23582336
Xiong H, Wang S, Kobayashi K, Jiang Y, Wang J, Chang X, Yuan Y, Liu J, Toda T, Fukuyama Y, Wu X
Am J Med Genet A 2009 Nov;149A(11):2403-8. doi: 10.1002/ajmg.a.33057. PMID: 19842201
Lee J, Lee BL, Lee M, Kim JH, Kim JW, Ki CS
J Neurol Sci 2009 Jun 15;281(1-2):122-4. Epub 2009 Mar 25 doi: 10.1016/j.jns.2009.02.373. [Epub ahead of print] PMID: 19324374
Saito K
Prenat Diagn 2006 May;26(5):415-7. doi: 10.1002/pd.1426. PMID: 16570239
Aida N, Yagishita A, Takada K, Katsumata Y
AJNR Am J Neuroradiol 1994 Oct;15(9):1755-9. PMID: 7847224

Therapy

Touznik A, Lee JJ, Yokota T
Expert Opin Biol Ther 2014 Jun;14(6):809-19. Epub 2014 Mar 12 doi: 10.1517/14712598.2014.896335. [Epub ahead of print] PMID: 24620745
Godfrey C, Escolar D, Brockington M, Clement EM, Mein R, Jimenez-Mallebrera C, Torelli S, Feng L, Brown SC, Sewry CA, Rutherford M, Shapira Y, Abbs S, Muntoni F
Ann Neurol 2006 Nov;60(5):603-10. doi: 10.1002/ana.21006. PMID: 17044012

Prognosis

Ismail S, Schaffer AE, Rosti RO, Gleeson JG, Zaki MS
Gene 2014 Apr 15;539(2):279-82. Epub 2014 Feb 13 doi: 10.1016/j.gene.2014.01.070. [Epub ahead of print] PMID: 24530477
Alkan O, Kizilkilic O, Yildirim T
Cerebellum 2009 Sep;8(3):355-65. Epub 2009 Apr 1 doi: 10.1007/s12311-009-0104-x. [Epub ahead of print] PMID: 19337779
Chang W, Winder TL, LeDuc CA, Simpson LL, Millar WS, Dungan J, Ginsberg N, Plaga S, Moore SA, Chung WK
Prenat Diagn 2009 Jun;29(6):560-9. doi: 10.1002/pd.2238. PMID: 19266496Free PMC Article
Beggs AH, Neumann PE, Arahata K, Arikawa E, Nonaka I, Anderson MS, Kunkel LM
Proc Natl Acad Sci U S A 1992 Jan 15;89(2):623-7. PMID: 1731332Free PMC Article
Stern LM, Albertyn L, Manson JI
Dev Med Child Neurol 1990 Sep;32(9):808-13. PMID: 2227144

Clinical prediction guides

Yamamoto T, Kato Y, Karita M, Takeiri H, Muramatsu F, Kobayashi M, Saito K, Osawa M
Acta Neuropathol 2002 Sep;104(3):217-24. Epub 2002 Jun 21 doi: 10.1007/s00401-002-0542-8. [Epub ahead of print] PMID: 12172906
Ishii H, Hayashi YK, Nonaka I, Arahata K
Neuromuscul Disord 1997 May;7(3):191-7. PMID: 9185184
Beggs AH, Neumann PE, Arahata K, Arikawa E, Nonaka I, Anderson MS, Kunkel LM
Proc Natl Acad Sci U S A 1992 Jan 15;89(2):623-7. PMID: 1731332Free PMC Article
Takada K, Nakamura H
Brain Dev 1990;12(6):774-8. PMID: 2092587
Takada K, Rin YS, Kasagi S, Sato K, Nakamura H, Tanaka J
Acta Neuropathol 1986;71(3-4):228-32. PMID: 3799138

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