IllnessWalker-Warburg syndrome, differential diagnosis

NGS +

Walker-Warburg syndrome affects the development of the muscles, brain and eyes. It is the most severe of the congenital muscular dystrophies with muscle hypotonia, weakness usually immediately after birth or in infancy, and later atrophy. Most affected individuals also have cobblestone lissencephaly as well as hydrocephalus and do not survive past the age of three years. Ocular abnormalities are also characteristic, including microphthalmia or buphthalmos, cataracts and retinal dysplasia. Mutations in genes associated with Walker-Warburg syndrome prevent glycosylation of α-dystroglycan. These so-called dystroglycanopathies are virtually always inherited in an autosomal recessive manner. Currently, definitive and reliable molecular genetic diagnoses are achieved in at least 40-60% of patients, depending on previous clinical findings. Clinical diagnosis cannot be excluded by a negative molecular genetic result.

References: https://www.ncbi.nlm.nih.gov/books/NBK1206/

https://www.ncbi.nlm.nih.gov/books/NBK97333/

• Alias: Congenital muscular dystrophy-dystroglycanopathy with brain + eye anomalies
• Alias: Dystroglycanopathy
• Alias: HARD syndrome [Hydrocephalus, Agyria, Retinal Dysplasia, with/-out Encephalocele]
• Alias: MEB [Muscle Eye Brain disease]
• Allelic: Angiopathy, hereditary, with nephropathy, aneurysms + muscle cramps (COL4A1)
• Allelic: Brain small vessel disease with/-out ocular anomalies (COL4A1)
• Allelic: Cardiomyopathy, dilated, 1X (FKTN)
• Allelic: Microangiopathy + leukoencephalopathy, pontine, AD (COL4A1)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 1 (POMT1)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 12 (POMK)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 14 (GMPPB)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 2 (POMT2)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 3 (POMGNT1)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 4 (FKTN)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 5 (FKRP)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 7 (CRPPA)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 8 (POMGNT2)
• Allelic: Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 9 (DAG1)
• Allelic: Retinitis pigmentosa 76 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 10 (RXYLT1/TMEM5)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 11 (B3GALNT2)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 12 (POMK)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 13 (B4GAT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 6 (LARGE1)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 7 (CRPPA)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 8 (POMGNT2)
• Muscular dystrophy-dystroglycanopathy, cong. with brain + eye anomalies, type A, 9 (DAG1)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, cong. with mental retardation, type B, 6 (LARGE1)
• Muscular dystrophy-dystroglycanopathy, cong. with/-out mental retardation, type B, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, cong. without mental retardation, type B, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, limb-girdle, type C, 7 (ISPD)