- Open Access
Orphanet Journal of Rare Diseasesvolume 1, Article number: 29 (2006)
Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of α-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. 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. No specific treatment is available. Management is only supportive and preventive.
Cerebroocular dysgenesis (COD)
Cerebroocular dysplasia-muscular dystrophy (COD-MD) syndrome
Hydrocephalus-Agyria-Retinal Dysplasia (HARD) Syndrome
HARD +/- syndrome
Walker-Warburg Syndrome (WWS) is a genetically heterogeneous disease presenting with congenital muscular dystrophy, type II lissencephaly, hydrocephalus, cerebellar malformations and eye abnormalities [1–4]. So far, only 10%–20% of cases can be confirmed by DNA analysis of mutations in the Protein O-Mannosyltransferase 1 (POMT1) gene [5–7]. DNA analysis in other genes besides POMT1 can be confirmative: fukutin [8, 9]; FKRP  and POMT2 .
WWS is a rare disease with a worldwide distribution; however, the overall incidence is unknown. A survey in north-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births .
WWS is the most severe congenital muscular dystrophy (CMD). Symptoms and signs are already present at birth and early infancy, and occasionally can be detected prenatally with imaging techniques. WWS is associated with generalized hypotonia, muscle weakness, developmental delay with mental retardation and, in some children, seizures. There may be a variety of anterior eye anomalies (cataracts, shallow anterior chamber, microcornea and microphthalmia, and lens defects) and a spectrum of posterior eye anomalies (retinal detachment or dysplasia, hypoplasia or atrophy of the optic nerve and macula and coloboma). Glaucoma or buphthalmos may be present. Brain abnormalities include migrational defect with type II lissencephaly (cobblestone type), hydrocephalus, vermal or general cerebellar hypoplasia and flat brainstem with small pyramids. White matter shows hypomyelination. Additional brain anomalies such as hypoplasia/agenesis of corpus callosum, occipital encephalocele and Dandy-Walker malformation have been described. Other recognized associated anomalies are small penis, undescended testes, and, rarely, other facial dysmorphic features such as low set or prominent ears and cleft lip or palate.
Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered α-dystroglycan.
The dystrophin glycoprotein complex (DGC) is an assembly of proteins spanning the sarcolemma of skeletal muscle cells [13–15]. Defects in the DGC appear to play critical roles in several muscular dystrophies due to disruption of basement membrane organization [16, 17]. Dystroglycan (dystrophin-associated glycoprotein), a major component of the DGC, is expressed in many cell types, and is synthesized as a precursor propeptide that is post-translationally cleaved and differentially glycosylated to yield α- and β-dystroglycans. There is evidence suggesting that the tetrasaccharide NeuAcα2, 3Galβ1, 4GlcNAcβ1, 2Manα1-O-Ser/Thr present on α-dystroglycan is required for the binding of laminin and other ligands to α-dystroglycan [18–20].
Mutations interfering with the binding of extracellular ligands to α-dystroglycan may lead to weakened anchorage of muscle fibers to the extracellular matrix with very early (i.e., embryonic) and rapid muscle dysfunction and necrosis . This process is responsible for an etiologically heterogeneous group of autosomal recessive CMDs with associated brain and eye abnormalities [5, 21–28]. Immunohistochemical studies using antibodies against α-dystroglycan (e.g. VIA4-1 directed against the glycans on α-dystroglycan) have revealed that these CMDs are associated with deficient immunostaining of α-dystroglycan in the basal lamina of skeletal muscles [29–33]. The data indicate that α-dystroglycan is underglycosylated in muscle from these patients .
A genome-wide linkage analysis in 10 consanguineous families with WWS indicated the existence of at least three WWS loci . Since protein O-mannoside β1,2-N-acetylglucosaminyltransferase (POMGnT1) had recently been implicated as the cause of muscle-eye-brain disease (MEB) [35–37], Beltran-Valero de Bernabe et al.  screened WWS patients for mutations in the gene encoding protein O-mannosyltransferase (POMT) that attaches mannose via a O-glycosidic link to the Ser/Thr residues of α-dystroglycan, thereby synthesizing the substrate for POMGnT1. Homozygous mutations at the POMT1 locus on chromosome 9q34 were found in 5 out of 15 consanguineous families with WWS. Sequencing of the POMT1 gene revealed mutations in 6 out of 30 unrelated patients with WWS . Of the five mutations identified, two were nonsense mutations, two were frameshift mutations and one was a missense mutation. Other mutations and phenotype-genotype correlations were reported in 2006 . More severe phenotypes were associated with highly disruptive homozygous mutations, while mild compound heterozygous mutations in one or both alleles were associated with a less severe phenotype and longer life span.
In another series of 30 patients with classic WWS, two potential novel heterozygous mutations in the POMT1 gene were found in two patients from non-consanguineous parents . However, the other 28 patients failed to show any POMT1 mutations. Linkage analysis in six consanguineous families with WWS showed that defective POMT1 was an uncommon cause of WWS in this population (the incidence of coding region mutations was less than 7%).
One other child with the WWS phenotype was reported to have a homozygous null mutation in the fukutin gene and another child a homozygous C953T missense mutation in the FKRP gene [8, 10]. A fourth causative gene for WWS was found in 2005, when three homozygous mutations in the POMT2 gene were detected in WWS patients from three families .
In all tissues tested, POMT1 mRNA is expressed as a 3.1 kb transcript, with highest levels in the testes and fetal brain. Alternative splicing of several exons in all tissues predicts the generation of several protein isoforms. A method for measuring POMT activity in mammalian cells has been developed . However, recombinant POMT1 was found to be inactive. It turns out that the human genome contains two genes encoding POMT (POMT1 and POMT2). Neither recombinant protein by itself shows enzyme activity. Mixing of recombinant forms of the two proteins also fails to result in an active enzyme. The two genes must be co-expressed to obtain an active POMT enzyme complex [40–42].
Homozygous inactivation of the POMT1 gene in the mouse is embryonic lethal with developmental arrest around embryonic day (E) 7.5 and death between E7.5 and E9.5 . The POMT1(-/-) embryos present defects in the formation of Reichert's membrane, the first basement membrane to form in the embryo. The failure of this membrane to form appears to be the result of abnormal glycosylation and maturation of dystroglycan that may impair recruitment of laminin, a structural component required for the formation of Reichert's membrane in rodents.
Diagnostic methods and criteria
The diagnosis is established on the basis of four criteria:
• congenital muscular dystrophy characterized by hypoglycosylation of α-dystroglycan
• high creatine kinase level
• anterior or posterior eye anomalies
• migrational brain defect with type II lissencephaly and hydrocephalus
• abnormal brainstem/cerebellum
Mutations or gene loci are currently unknown in majority of patients. Only 10 – 20% of cases have a mutation in the POMT1, POMT2, fukutin or FKRP genes.
The diagnostic criteria for WWS were established on the basis of data obtained from 21 patients and an additional 42 patients from the literature . Four abnormalities were present in all patients checked for these anomalies: type II lissencephaly (21/21), cerebellar malformation (20/20), retinal malformation (18/18), and CMD (14/14). Two other frequently observed abnormalities, ventricular dilatation with or without hydrocephalus (20/21) and anterior chamber malformation (16/21), were helpful but not obligatory for diagnosis because they were not constant. All other abnormalities occurred less frequently. Congenital macrocephaly with hydrocephalus (11/19) was more common than congenital microcephaly (3/19). Dandy-Walker malformation (10/19) was sometimes associated with posterior cephalocele (5/21). Additional abnormalities included slit-like ventricles (1/21), microphthalmia (8/21), ocular colobomas (3/15), congenital cataracts (7/20), and genital anomalies in males (5/8).
The differential diagnoses include:
• Fukuyama congenital muscular dystrophy (FCMD)
• CMD type 1C
• CMD type 1D
• Muscle-eye-brain disease (MEB)
• Congenital muscular dystrophies without brain and eye abnormalities
FCMD and MEB are associated with similar but less severe brain and eye changes and CMD. Patients with CMD type 1C may have variable findings on brain magnetic resonance imaging (MRI) and eye exam. The only patient with CMD type 1D reported so far has milder brain abnormalities than those seen in WWS.
WWS is an autosomal recessive disorder. In families with one affected child, the risk of having another child with the disease is 25%.
Antenatal molecular diagnosis might be possible in families with known mutations. Antenatal ultrasound can also be helpful in families in whom the molecular defect is unknown. Hydrocephalus has been detected by ultrasound as early as at 13 weeks of gestation  and occipital encephalocele, not always present, has been detected at 18 weeks of gestation .
Management including treatment
Management is only supportive and preventive. If seizures develop, they usually need to be treated with anticonvulsants. A few children require a neurosurgical procedure such as shunting of hydrocephalus or encephalocele operation. Physical therapy can be offered to facilitate development or prevent worsening of contractures although its efficacy has not been established. Feeding needs to be monitored and supplemental nasogastric or gastric tube feeding provided in some cases. Detailed eye assessment is also needed.
The condition is usually lethal within the first few months of life, with almost all children dying by the age of three.
There are no known candidate genes for 80%–90% of children with WWS. Although the POMT1 gene involved in WWS implies a defect in O-mannosylation of α-dystroglycan, the exact pathophysiology of this disorder is not fully understood. As new genetic defects associated with WWS are reported, a better genotype-phenotype correlation should be established.
Other interesting issues
The following research papers have helped to shed light on Walker-Warburg syndrome:
Role of dystroglycan in pathogenesis 
In mice, brain-selective deletion of dystroglycan is sufficient to cause CMD-like brain malformations, including disarray of cerebral cortical layering, fusion of cerebral hemispheres and cerebellar folia, and aberrant migration of granule cells. Additionally, high-affinity binding to laminin is lost, and there are discontinuities in the pial surface basal lamina (glia limitans) that probably underlie the neuronal migration errors. Furthermore, mutant mice have severely blunted hippocampal long-term potentiation with electrophysiologic characterization indicating that dystroglycan might have a postsynaptic role in learning and memory.
The data strongly support the hypothesis that defects in dystroglycan are central to the pathogenesis of structural and functional brain abnormalities seen in CMD.
Pathogenetic mechanisms underlying degeneration 
Immunohistochemical and electron microscopy were carried out on muscle obtained by biopsy from a patient with WWS carrying a homozygous frameshift mutation in POMT1. The α-dystroglycan glycosylated epitope was not detected in muscle fibers or intramuscular peripheral nerves. Laminin-α2 chain and perlecan were reduced in muscle fibers but well preserved in intramuscular peripheral nerves. The basal lamina in several muscle fibers showed discontinuities and detachment from the plasmalemma. Most nuclei, including myonuclei and satellite cell nuclei, showed detachment or complete absence of peripheral heterochromatin from the nuclear envelope. Apoptotic changes were detected in 3% of muscle fibers.
The particular combination of basal lamina and nuclear changes suggests that a complex pathogenetic mechanism, involving several subcellular compartments, underlies the muscle degenerative process in WWS.
Genetic heterogeneity 
Immunohistochemistry and immunoblotting showed almost complete absence of α-dystroglycan and a mild reduction of laminin-α2 in two patients with WWS. In contrast, immunohistochemical labeling of perlecan and collagen VI was normal. Linkage analysis excluded the POMT1 locus, confirming that WWS is a genetically heterogeneous condition.
It was suggested that disruption of the α-dystroglycan/laminin-α2 axis in the basal lamina may play a role in the degeneration of muscle fibers in WWS patients who do not have a mutation in POMT1.
Walker AE: Lissencephaly. Arch Neurol Psychiat. 1942, 48: 13-29.
Warburg M: The heterogeneity of microphthalmia in the mentally retarded. Birth Defects Orig Art Ser. 1971, 7: 136-154.
Warburg M: Heterogeneity of congenital retinal non-attachment, falciform folds and retinal dysplasia. A guide to genetic counselling. Hum Hered. 1976, 26: 137-148.
Warburg M: Hydrocephaly, congenital retinal nonattachment, and congenital falciform fold. Am J Ophthalmol. 1978, 85: 88-94.
Dobyns WB, Pagon RA, Armstrong D, Curry CJ, Greenberg F, Grix A, Holmes LB, Laxova R, Michels VV, Robinow M, Zimmerman RL: Diagnostic criteria for Walker-Warburg syndrome. Am J Med Genet. 1989, 32: 195-210. 10.1002/ajmg.1320320213.
Beltrán-Valero De Bernabé D, Currier S, Steinbrecher A, Celli J, Van Beusekom E, Van Der Zwaag B, Kayserili H, Merlini L, Chitayat D, Dobyns WB, Cormand B, Lehesjoki AE, Cruces J, Voit T, Walsh CA, Van Bokhoven H, Brunner HG: Mutations in the O-Mannosyltransferase Gene POMT1 Give Rise to the Severe Neuronal Migration Disorder Walker-Warburg Syndrome. Am J Hum Genet. 2002, 71: 1033-1043. 10.1086/342975.
van Reeuwijk J, Brunner HG, Van Bokhoven H: Glyc-O-genetics of Walker-Warburg syndrome. Clin Genet. 2005, 67: 281-289. 10.1111/j.1399-0004.2004.00368.x.
Beltrán-Valero de Bernabé D, van Bokhoven E, van Beusekom E, Van Den Akker W, Kant S, Dobyns WB, Cormand B, Currier S, Hamel B, Talim B, Topaloglu H, Brunner HG: A homozygous nonsense mutation in the Fukutin gene causes a Walker-Warburg syndrome phenotype. J Med Genet. 2003, 40: 845-848. 10.1136/jmg.40.11.845.
Silan F, Yoshioka M, Kobayashi K, Simsek E, Tunc M, Alper M, Cam M, Guven A, Fukuda , Kinoshita M, Kocabay K, Toda T: A new mutation of the fukutin gene in a non-Japanese patient. Ann Neurol. 2003, 53: 392-396. 10.1002/ana.10491.
Beltran-Valero de Bernabe D, Voit T, Longman C, Steinbrecher A, Straub V, Yuva Y, Herrmann R, Sperner J, Korenke C, Diesen C, Dobyns WB, Brunner HG, van Bokhoven H, Brockington M, Muntoni F: Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome. J Med Genet. 2004, 41: e61-10.1136/jmg.2003.013870.
van Reeuwijk J, Janssen M, van den Elzen C, Beltran-Valero de Bernabe D, Sabatelli P, Merlini L, Boon M, Scheffer H, Brockington M, Muntoni F, Huynen MA, Verrips A, Walsh CA, Barth PG, Brunner HG, van Bokhoven H: POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome. J Med Genet. 2005, 42: 907-912. 10.1136/jmg.2005.031963.
Mostacciuolo ML, Miorin M, Martinello F, Angelini C, Perini P, Trevisan CP: Genetic epidemiology of congenital muscular dystrophy in a sample from the north-east Italy. Hum Genet. 1996, 97: 277-279. 10.1007/BF02185752.
Ervasti JM, Ohlendieck K, Kahl SD, Gaver MG, Campbell KP: Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature. 1990, 345: 315-319. 10.1038/345315a0.
Ervasti JM, Campbell KP: Membrane organization of the dystrophin-glycoprotein complex. Cell. 1991, 66: 1121-1131. 10.1016/0092-8674(91)90035-W.
Winder SJ: The complexities of dystroglycan. Trends Biochem Sci. 2001, 26: 118-124. 10.1016/S0968-0004(00)01731-X.
Williamson RA, Henry MD, Daniels KJ, Hrstka RF, Lee JC, Sunada Y, Ibraghimov-Beskrovnaya O, Campbell KP: Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice. Hum Mol Genet. 1997, 6: 831-841. 10.1093/hmg/6.6.831.
Henry MD, Campbell KP: A role for dystroglycan in basement membrane assembly. Cell. 1998, 95: 859-870. 10.1016/S0092-8674(00)81708-0.
Yamada H, Chiba A, Endo T, Kobata A, Anderson LV, Hori H, Fukuta-Ohi H, Kanazawa I, Campbell KP, Shimizu T, Matsumura K: Characterization of dystroglycan-laminin interaction in peripheral nerve. J Neurochem. 1996, 66: 1518-1524.
Chiba A, Matsumura K, Yamada H, Inazu T, Shimizu T, Kusunoki S, Kanazawa I, Kobata A, Endo T: Structures of sialylated O-linked oligosaccharides of bovine peripheral nerve alpha-dystroglycan. The role of a novel O-mannosyl-type oligosaccharide in the binding of alpha-dystroglycan with laminin. J Biol Chem. 1997, 272: 2156-2162. 10.1074/jbc.272.4.2156.
Endo T: O-mannosyl glycans in mammals. Biochim Biophys Acta. 1999, 1473: 237-246.
Dubowitz V, Fardeau M: Proceedings of the 27th ENMC sponsored workshop on congenital muscular dystrophy. 22–24 April The Netherlands. Neuromuscul Disord. 1995, 5: 253-258. 10.1016/0960-8966(95)90011-X.
Voit T, Sewry CA, Meyer K, Hermann R, Straub V, Muntoni F, Kahn T, Unsold R, Helliwell TR, Appleton R, Lenard HG: Preserved merosin M-chain (or laminin-alpha 2) expression in skeletal muscle distinguishes Walker-Warburg syndrome from Fukuyama muscular dystrophy and merosin-deficient congenital muscular dystrophy. Neuropediatrics. 1995, 26: 148-155.
Haltia M, Leivo I, Somer H, Pihko H, Paetau A, Kivela T, Tarkkanen A, Tome F, Engvall E, Santavuori P: Muscle-eye-brain disease: a neuropathological study. Ann Neurol. 1997, 41: 173-180. 10.1002/ana.410410208.
Vajsar J, Chitayat D, Becker LE, Ho M, Ben-Zeev B, Jay V: Severe classical congenital muscular dystrophy and merosin expression. Clin Genet. 1998, 54: 193-198.
Santavuori P, Valanne L, Autti T, Haltia M, Pihko H, Sainio K: Muscle-eye-brain disease: clinical features, visual evoked potentials and brain imaging in 20 patients. Eur J Paediatr Neurol. 1998, 2: 41-47. 10.1016/1090-3798(98)01004-1.
Culligan KG, Mackey AJ, Finn DM, Maguire PB, Ohlendieck K: Role of dystrophin isoforms and associated proteins in muscular dystrophy. Int J Mol Med. 1998, 2: 639-648.
Dubowitz V: 68th ENMC international workshop (5th international workshop): On congenital muscular dystrophy, 9–11 April 1999, Naarden, The Netherlands. Neuromuscul Disord. 1999, 9: 446-454. 10.1016/S0960-8966(99)00074-7.
Cormand B, Pihko H, Bayes M, Valanne L, Santavuori P, Talim B, Gershoni-Baruch R, Ahmad A, van Bokhoven H, Brunner HG, Voit T, Topaloglu H, Dobyns WB, Lehesjoki AE: Clinical and genetic distinction between Walker-Warburg syndrome and muscle-eye-brain disease. Neurology. 2001, 56: 1059-1069.
Hewitt JE, Grewal PK: Glycosylation defects in inherited muscle disease. Cell Mol Life Sci. 2003, 60: 251-258. 10.1007/s000180300020.
Martin-Rendon E, Blake DJ: Protein glycosylation in disease: new insights into the congenital muscular dystrophies. Trends Pharmacol Sci. 2003, 24: 178-183. 10.1016/S0165-6147(03)00050-6.
Martin PT, Freeze HH: Glycobiology of neuromuscular disorders. Glycobiology. 2003, 13: 67R-75R. 10.1093/glycob/cwg077.
Grewal PK, Hewitt J: Glycosylation defects: a new mechanism for muscular dystrophy?. Hum Mol Genet. 2003, 12 (Spec No 2): R259-264. 10.1093/hmg/ddg272.
Endo T, Toda T: Glycosylation in congenital muscular dystrophies. Biol Pharm Bull. 2003, 26: 1641-1647. 10.1248/bpb.26.1641.
Muntoni F, Brockington M, Blake DJ, Torelli S, Brown SC: Defective glycosylation in muscular dystrophy. Lancet. 2002, 360: 1419-1421. 10.1016/S0140-6736(02)11397-3.
Yoshida A, Kobayashi K, Manya H, Taniguchi K, Kano H, Mizuno M, Inazu T, Mitsuhashi H, Takahashi S, Takeuchi M, Herrmann R, Straub V, Talim B, Voit T, Topaloglu H, Toda T, Endo T: Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Dev Cell. 2001, 1: 717-724. 10.1016/S1534-5807(01)00070-3.
Taniguchi K, Kobayashi K, Saito K, Yamanouchi H, Ohnuma A, Hayashi YK, Manya H, Jin DK, Lee M, Parano E, Falsaperla R, Pavone P, Van Coster R, Talim B, Steinbrecher A, Straub V, Nishino I, Topaloglu H, Voit T, Endo T, Toda T: Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease. Hum Mol Genet. 2003, 12: 527-534. 10.1093/hmg/ddg043.
Manya H, Sakai K, Kobayashi K, Taniguchi K, Kawakita M, Toda T, Endo T: Loss-of-function of an N-acetylglucosaminyltransferase, POMGnT1, in muscle-eye-brain disease. Biochem Biophys Res Commun. 2003, 306: 93-97. 10.1016/S0006-291X(03)00924-0.
van Reeuwijk J, Maugenre S, van den Elzen C, Virrips A, Bertini E, Muntoni F, Merlini L, Scheffer H, Brunner HG, Guicheney P, van Bokhoven H: The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation. Hum Mutat. 2006, 27: 453-459. 10.1002/humu.20313.
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: Mutations in POMT1 are found in a minority of patients with Walker-Warburg syndrome. Am J Med Genet A. 2005, 133: 53-57.
Akasaka-Manya K, Manya H, Endo T: Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation. Biochem Biophys Res Commun. 2004, 325: 75-79. 10.1016/j.bbrc.2004.10.001.
Ichimiya T, Manya H, Ohmae Y, Yoshida H, Takahashi K, Ueda R, Endo T, Nishihara S: The twisted abdomen phenotype of Drosophila POMT1 and POMT2 mutants coincides with their heterophilic protein O-mannosyltransferase activity. J Biol Chem. 2004, 279: 42638-42647. 10.1074/jbc.M404900200.
Manya H, Chiba A, Yoshida A, Wang X, Chiba Y, Jigami Y, Margolis RU, Endo T: Demonstration of mammalian protein O-mannosyltransferase activity: coexpression of POMT1 and POMT2 required for enzymatic activity. Proc Natl Acad Sci USA. 2004, 101: 500-505. 10.1073/pnas.0307228101.
Willer T, Prados B, Falcon-Perez JM, Renner-Muller I, Przemeck GK, Lommel M, Coloma A, Valero MC, De Angelis MH, Tanner W, Wolf E, Strahl S, Cruces J: Targeted disruption of the Walker-Warburg syndrome gene Pomt1 in mouse results in embryonic lethality. Proc Natl Acad Sci USA. 2004, 101: 14126-14131. 10.1073/pnas.0405899101.
Gasser B, Lindner V, Dreyfus M, Feidt X, Leissner P, Treisser A, Stoll C: Prenatal diagnosis of Walker-Warburg syndrome in three sibs. Am J Med Genet. 1998, 76: 107-110. 10.1002/(SICI)1096-8628(19980305)76:2<107::AID-AJMG1>3.0.CO;2-Q.
Farrell SA, Toi A, Leadman ML, Davidson RG, Caco C: Prenatal diagnosis of retinal detachment in Walker-Warburg syndrome. Am J Med Genet. 1987, 28: 619-624. 10.1002/ajmg.1320280309.
Moore SA, Saito F, Chen J, Michele DE, Henry MD, Messing A, Cohn RD, Ross-Barta SE, Westra S, Williamson RA, Hoshi T, Campbell KP: Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature. 2002, 418: 422-425. 10.1038/nature00838.
Sabatelli P, Columbaro M, Mura I, Capanni C, Lattanzi G, Maraldi NM, Beltran-Valero de Barnabe D, van Bokoven H, Squarzoni S, Merlini L: Extracellular matrix and nuclear abnormalities in skeletal muscle of a patient with Walker-Warburg syndrome caused by POMT1 mutation. Biochim Biophys Acta. 2003, 1638: 57-62.
Jimenez-Mallebrera C, Torelli S, Brown SC, Feng L, Brockington M, Sewry CA, Beltran-Valero De Bernabe D, Muntoni F: Profound skeletal muscle depletion of alpha-dystroglycan in Walker-Warburg syndrome. Eur J Paediatr Neurol. 2003, 7: 129-137. 10.1016/S1090-3798(03)00042-4.