Walker–Warburg syndrome
| Walker–Warburg syndrome | |
|---|---|
| Other names | HARD syndrome, Warburg syndrome |
 | |
| Walker–Warburg syndrome has an autosomal recessive pattern of inheritance. | |
| Specialty | Ophthalmology, neurology, medical genetics  |
| Frequency | 0.0001% |
Walker–Warburg syndrome (WWS), also called Warburg syndrome, Chemke syndrome, HARD syndrome (Hydrocephalus, Agyria and Retinal Dysplasia), Pagon syndrome, cerebroocular dysgenesis (COD) or cerebroocular dysplasia-muscular dystrophy syndrome (COD-MD),[1] is a rare form of autosomal recessive congenital muscular dystrophy.[2] It is associated with brain (lissencephaly, hydrocephalus, cerebellar malformations) and eye abnormalities.[3] This condition has a worldwide distribution. Walker-Warburg syndrome is estimated to affect 1 in 60,500 newborns worldwide.[4]
Presentation
[edit]
The clinical manifestations present at birth are generalized hypotonia, muscle weakness, developmental delay with intellectual disability and occasional seizures.[5] The congenital muscular dystrophy is characterized by hypoglycosylation of α-dystroglycan. Those born with the disease also experience severe ocular and brain defects. Half of all children with WWS are born with encephalocele, which is a gap in the skull that will not seal. The meninges of the brain protrude through this gap due to the neural tube failing to close during development. A malformation of the a baby's cerebellum is often a sign of this disease. Common ocular issues associated with WWS are abnormally small eyes and retinal abnormalities cause by an underdeveloped light-sensitive area in the back of the eye.[6]
Genetics
[edit]Several genes have been implicated in the etiology of Walker–Warburg syndrome, and following genes are: POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, CRPPA, GTDC2, DAG1, RXYLT1, B3GALNT2, POMK, B3GNT1, GMPPB.[1] All these enzymes (except for DAG1, which is dystroglycan itself) participate in glycosylation of α-dystroglycan, which is important for the proper function of the protein.[7] DAG1 mutations can cause either hypoglycosalation or pertubated maturation/transport to plasma membrane.[7]
First gene to cause WWS, POMT1, was discovered in 2001 by de Bernabe and colleagues.[8]
Diagnosis
[edit]Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered α-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown.[9]
Prognosis
[edit]No specific treatment is available. Management is only supportive and preventive. Those who are diagnosed with the disease often die within the first few months of life. Almost all children with the disease die by the age of three.[9]
Eponym
[edit]WWS is named for Arthur Earl Walker and Mette Warburg.[10][11][12] Its alternative names include Chemke’s syndrome and Pagon’s syndrome, named after Juan M. Chemke and Roberta A. Pagon.[10]
References
[edit]- 1 2 "Muscular Dystrophy-Dystroglycanopathy (Congenital With Brain and Eye Anomalies), Type a, 1; MDDGA1". Online Mendelian Inheritance in Man (OMIM). 236670.
- ↑ Vajsar J, Schachter H (August 2006). "Walker-Warburg syndrome". Orphanet Journal of Rare Diseases. 1 29. doi:10.1186/1750-1172-1-29. PMC 1553431. PMID 16887026.
- ↑ "Walker-Warburg syndrome". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. U.S. National Institutes of Health. Archived from the original on January 24, 2017. Retrieved 2018-04-09.
- ↑ "Walker-Warburg syndrome". MedlinePlus Genetics. U.S. National Library of Medicine. Retrieved 2023-03-14.
- ↑ "Walker-Warburg syndrome". Genetics Home Reference. U.S. National Library of Medicine. Retrieved 2018-04-17.
- ↑ Weiss TC (1 February 2023) [6 March 2010]. "Walker-Warburg Syndrome - Facts and Information". Disabled World.
- 1 2 Nickolls AR, Bönnemann CG (2018-12-19). "The roles of dystroglycan in the nervous system: insights from animal models of muscular dystrophy". Disease Models & Mechanisms. 11 (12): dmm035931. doi:10.1242/dmm.035931. ISSN 1754-8411. PMC 6307911. PMID 30578246.
- ↑ Beltrán-Valero de Bernabé D, Currier S, Steinbrecher A, Celli J, van Beusekom E, van der Zwaag B, et al. (November 2002). "Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome". American Journal of Human Genetics. 71 (5): 1033–1043. doi:10.1086/342975. PMC 419999. PMID 12369018.
- 1 2 Vajsar J, Schachter H (August 2006). "Walker-Warburg syndrome". Orphanet Journal of Rare Diseases. 1 29. doi:10.1186/1750-1172-1-29. PMC 1553431. PMID 16887026.
- 1 2 "Walker-Warburg syndrome". Whonamedit?.
- ↑ Walker AE (1942). "Lissencephaly". Archives of Neurology and Psychiatry. 48: 13–29. doi:10.1001/archneurpsyc.1942.02290070023002.
- ↑ Warburg M (March 1971). "The heterogeneity of microphthalmia in the mentally retarded". Birth Defects Original Article Series. 7 (3): 136–154. PMID 4950916.