IllnessMuscle-eye-brain disease, differential diagnosis

NGS +

Congenital muscular dystrophy dystroglycanopathies with brain and eye abnormalities, type A, include the most severe course, Walker-Warburg syndrome, Fukuyama disease and the somewhat less severe muscle-eye-brain diseases (MEB), all of which are characterized by brain and eye malformations, marked mental retardation, congenital muscular dystrophy and often early death. MEBs have a phenotypic spectrum of approximately 14 quite similar disorders due to defective glycosylation of DAG1, and they are also grouped under the term dystroglycanopathies. Allelic disorders are referred to as muscular dystrophy dystroglycanopathy, congenital with mental retardation, type B, and/or muscular dystrophy dystroglycanopathy, limb girdle, type C. Walker-Warburg patients typically develop cobblestone lissencephaly with cerebral and cerebellar cortical dysplasia, microphthalmia, buphthalmos, cataract and visual disturbances. Developmental delays are common in all forms of MEB, seizures are observed in 2/3 of cases, while slowly progressive cardiac involvement appears less pronounced in MEB than in Duchenne muscular dystrophy. Inheritance is autosomal recessive in all forms. The DNA diagnostic yield is up to 66% and more. Thus, a negative molecular genetic result does not exclude the clinical diagnosis with certainty.

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

https://www.aanem.org/getmedia/7b0620b5-c44f-48ad-9261-cc1b6a091757/CMD-complete-guideline-for-online-publication-(2).pdf

• Alias: Fukuyama congenital muscular dystrophy (FKTN)
• Alias: Muscle-eye-brain syndrome
• Alias: Muscular dystrophy-dystroglycanopathy, congenital with brain, eye anomalies
• Alias: Santavuori congenital muscular dystrophy (POMGNT1)
• Alias: Walker-Warburg syndrome (POMT1)
• Allelic: Cardiomyopathy, dilated, 1X (FKTN)
• Allelic: Muscular dystrophy-dystroglycanopathy, congen. with mental retard., type B, 1 (POMT1)
• Allelic: Muscular dystrophy-dystroglycanopathy, congen. with mental retard., type B, 14 (GMPPB)
• Allelic: Muscular dystrophy-dystroglycanopathy, congen. with mental retard., type B, 2 (POMT2)
• Allelic: Muscular dystrophy-dystroglycanopathy, congen. with mental retard., type B, 3 (POMGNT1)
• Allelic: Muscular dystrophy-dystroglycanopathy, congen. with mental retard., type B, 6 (LARGE1)
• Allelic: Muscular dystrophy-dystroglycanopathy, congen. with/-out mental retard., type B, 5 (FKRP)
• Allelic: Muscular dystrophy-dystroglycanopathy, congen. without mental retard., type B, 4 (FKTN)
• 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, congenital with brain + eye anomalies, type A, 1 (POMT1)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 10 (TMEM5)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 11 (B3GALNT2)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 12 (POMK)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 13 (B4GAT1)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 14 (GMPPB)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 2 (POMT2)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 3 (POMGNT1)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 4 (FKTN)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 5 (FKRP)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 6 (LARGE1)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 7 (CRPPA)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 8 (POMGNT2)
• Muscular dystrophy-dystroglycanopathy, congenital with brain + eye anomalies, type A, 9 (DAG1)