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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8(MDDGA8)

MedGen UID:
766727
Concept ID:
C3553813
Disease or Syndrome
Synonyms: MDDGA8; WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, GTDC2-RELATED
 
Gene (location): POMGNT2 (3p22.1)
 
Monarch Initiative: MONDO:0013904
OMIM®: 614830

Definition

Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. The phenotype includes the alternative clinical designation Walker-Warburg syndrome (WWS). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Manzini et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670). [from OMIM]

Clinical features

From HPO
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Cobblestone lissencephaly
MedGen UID:
96562
Concept ID:
C0431376
Congenital Abnormality
A form of lissencephaly characterized by an uneven cortical surface with a so called 'cobblestone' appearace. There are no distinguishable cortical layers.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Muscular dystrophy
MedGen UID:
44527
Concept ID:
C0026850
Disease or Syndrome
The term dystrophy means abnormal growth. However, muscular dystrophy is used to describe primary myopathies with a genetic basis and a progressive course characterized by progressive skeletal muscle weakness and wasting, defects in muscle proteins, and histological features of muscle fiber degeneration (necrosis) and regeneration. If possible, it is preferred to use other HPO terms to describe the precise phenotypic abnormalities.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Retinal dysplasia
MedGen UID:
48433
Concept ID:
C0035313
Congenital Abnormality
The presence of developmental dysplasia of the retina.

Recent clinical studies

Etiology

Murakami T, Sato T, Adachi M, Ishiguro K, Shichiji M, Tachimori H, Nagata S, Ishigaki K
Sci Rep 2021 Dec 20;11(1):24229. doi: 10.1038/s41598-021-03781-z. PMID: 34930981Free PMC Article
Ishigaki K, Ihara C, Nakamura H, Mori-Yoshimura M, Maruo K, Taniguchi-Ikeda M, Kimura E, Murakami T, Sato T, Toda T, Kaiya H, Osawa M
Neuromuscul Disord 2018 Oct;28(10):885-893. Epub 2018 Aug 10 doi: 10.1016/j.nmd.2018.08.001. PMID: 30220444
Zaum AK, Kolokotronis K, Kress W, Goebel HH, Rost S, Seeger J
Neuromuscul Disord 2018 Aug;28(8):671-674. Epub 2018 Jun 20 doi: 10.1016/j.nmd.2018.06.006. PMID: 30017359
Saito W, Namba T, Inoue G, Imura T, Miyagi M, Nakazawa T, Shirasawa E, Uchida K, Takaso M
J Orthop Sci 2017 Jul;22(4):658-664. Epub 2017 Mar 18 doi: 10.1016/j.jos.2017.02.005. PMID: 28325699
Cylwik B, Lipartowska K, Chrostek L, Gruszewska E
Acta Biochim Pol 2013;60(3):361-8. Epub 2013 Sep 19 PMID: 24051442

Diagnosis

Sato T, Awano H, Ishiguro K, Shichiji M, Murakami T, Shirakawa T, Matsuo M, Nagata S, Ishigaki K
Neuromuscul Disord 2021 Mar;31(3):194-197. Epub 2021 Jan 13 doi: 10.1016/j.nmd.2021.01.005. PMID: 33563515
Borisovna KO, Yurievna KA, Yurievich TK, Igorevna KO, Olegovich KD, Igorevna DA, Timofeevna BT, Vyacheslavovna ZN, Ivanovna SE, Alekseevich SP, Vladimirovich IV
BMC Pediatr 2019 Apr 8;19(1):98. doi: 10.1186/s12887-019-1470-2. PMID: 30961548Free PMC Article
Zaum AK, Kolokotronis K, Kress W, Goebel HH, Rost S, Seeger J
Neuromuscul Disord 2018 Aug;28(8):671-674. Epub 2018 Jun 20 doi: 10.1016/j.nmd.2018.06.006. PMID: 30017359
Sato T, Adachi M, Nakamura K, Zushi M, Goto K, Murakami T, Ishiguro K, Shichiji M, Saito K, Ikai T, Osawa M, Kondo I, Nagata S, Ishigaki K
Neuromuscul Disord 2017 Jan;27(1):45-49. Epub 2016 Sep 20 doi: 10.1016/j.nmd.2016.09.014. PMID: 27818010
Cylwik B, Lipartowska K, Chrostek L, Gruszewska E
Acta Biochim Pol 2013;60(3):361-8. Epub 2013 Sep 19 PMID: 24051442

Therapy

Murakami T, Sato T, Adachi M, Ishiguro K, Shichiji M, Tachimori H, Nagata S, Ishigaki K
Sci Rep 2021 Dec 20;11(1):24229. doi: 10.1038/s41598-021-03781-z. PMID: 34930981Free PMC Article
Hackmann T, Skidmore DL, MacManus B
A A Case Rep 2017 Oct 15;9(8):244-247. doi: 10.1213/XAA.0000000000000577. PMID: 28604469
Wilson RD, De Bie I, Armour CM, Brown RN, Campagnolo C, Carroll JC, Okun N, Nelson T, Zwingerman R, Audibert F, Brock JA, Brown RN, Campagnolo C, Carroll JC, De Bie I, Johnson JA, Okun N, Pastruck M, Vallée-Pouliot K, Wilson RD, Zwingerman R, Armour C, Chitayat D, De Bie I, Fernandez S, Kim R, Lavoie J, Leonard N, Nelson T, Taylor S, Van Allen M, Van Karnebeek C
J Obstet Gynaecol Can 2016 Aug;38(8):742-762.e3. doi: 10.1016/j.jogc.2016.06.008. PMID: 27638987

Prognosis

Corsten-Janssen N, Bouman K, Diphoorn JCD, Scheper AJ, Kinds R, El Mecky J, Breet H, Verheij JBGM, Suijkerbuijk R, Duin LK, Manten GTR, van Langen IM, Sijmons RH, Sikkema-Raddatz B, Westers H, van Diemen CC
Prenat Diagn 2020 Sep;40(10):1300-1309. Epub 2020 Jul 20 doi: 10.1002/pd.5781. PMID: 32627857Free PMC Article
Zaum AK, Kolokotronis K, Kress W, Goebel HH, Rost S, Seeger J
Neuromuscul Disord 2018 Aug;28(8):671-674. Epub 2018 Jun 20 doi: 10.1016/j.nmd.2018.06.006. PMID: 30017359
Sato T, Adachi M, Nakamura K, Zushi M, Goto K, Murakami T, Ishiguro K, Shichiji M, Saito K, Ikai T, Osawa M, Kondo I, Nagata S, Ishigaki K
Neuromuscul Disord 2017 Jan;27(1):45-49. Epub 2016 Sep 20 doi: 10.1016/j.nmd.2016.09.014. PMID: 27818010
Cooper M, Leventer R, Gillam L, Thomson Bowe K
Pediatr Neurol 2016 Nov;64:8-9. Epub 2015 Dec 10 doi: 10.1016/j.pediatrneurol.2015.11.012. PMID: 27692803
Currier SC, Lee CK, Chang BS, Bodell AL, Pai GS, Job L, Lagae LG, Al-Gazali LI, Eyaid WM, Enns G, Dobyns WB, Walsh CA
Am J Med Genet A 2005 Feb 15;133A(1):53-7. doi: 10.1002/ajmg.a.30487. PMID: 15637732

Clinical prediction guides

Sato T, Awano H, Ishiguro K, Shichiji M, Murakami T, Shirakawa T, Matsuo M, Nagata S, Ishigaki K
Neuromuscul Disord 2021 Mar;31(3):194-197. Epub 2021 Jan 13 doi: 10.1016/j.nmd.2021.01.005. PMID: 33563515
Ishigaki K, Ihara C, Nakamura H, Mori-Yoshimura M, Maruo K, Taniguchi-Ikeda M, Kimura E, Murakami T, Sato T, Toda T, Kaiya H, Osawa M
Neuromuscul Disord 2018 Oct;28(10):885-893. Epub 2018 Aug 10 doi: 10.1016/j.nmd.2018.08.001. PMID: 30220444
Saito W, Namba T, Inoue G, Imura T, Miyagi M, Nakazawa T, Shirasawa E, Uchida K, Takaso M
J Orthop Sci 2017 Jul;22(4):658-664. Epub 2017 Mar 18 doi: 10.1016/j.jos.2017.02.005. PMID: 28325699
Currier SC, Lee CK, Chang BS, Bodell AL, Pai GS, Job L, Lagae LG, Al-Gazali LI, Eyaid WM, Enns G, Dobyns WB, Walsh CA
Am J Med Genet A 2005 Feb 15;133A(1):53-7. doi: 10.1002/ajmg.a.30487. PMID: 15637732
Yamamoto T, Kato Y, Kawaguchi M, Shibata N, Kobayashi M
Med Electron Microsc 2004 Dec;37(4):200-7. doi: 10.1007/s00795-004-0260-5. PMID: 15614444

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