myelin-basic-protein and Abnormalities--Multiple

Partial deletion of genetic material from the long arm of chromosome 18 results in a syndrome with multisystemic involvement, including dysmorphic features, intellectual disability, cardiac malformations, endocrine abnormalities, immunodeficiency, musculoskeletal deformities, and variable neurologic manifestations. Hypomyelination has been reported in patients with chromosome 18q- and postulated to be secondary to deletion of the gene coding for myelin basic protein found at 18q23. Little however is reported on cerebral anomalies seen in patients with ring chromosome 18, an analogous syndrome but with expectedly more severe phenotype secondary to the combined deletions of genetic material from both the short (p-) and long arm (q-) of chromosome 18. We are reporting a case of a girl with ring chromosome 18 and deletions involving 18p11.32-18p11.21 and 18q21.31-18q23. The abnormalities observed on magnetic resonance imaging are discussed with a specific focus on the evolution and significance of associated white matter changes.

Topics: Abnormalities, Multiple; Child; Chromosome Aberrations; Chromosomes, Human, Pair 18; Female; Humans; Magnetic Resonance Imaging; Myelin Basic Protein; Ring Chromosomes

We studied 14 individuals with partial deletions of the long arm of chromosome 18, including terminal and interstitial de novo and inherited deletions. Study participants were examined clinically and by brain MRI. The size of the deletion was determined by segregation analysis using microsatellite markers. We observed that the phenotype was highly variable, even in two families with three 1st degree relatives. Among the 14 individuals, general intelligence varied from normal to severe mental retardation. The more common features of 18q-deletions (e.g., foot deformities, aural atresia, palatal abnormalities, dysmyelination, and nystagmus) were present in individuals lacking only the distal portion 18q22.3-qtel. Interstitial deletions exerted very heterogeneous effects on phenotype. In individuals with distal 18q22.3-q23 deletions, brain MRI was very distinctive with poor differentiation of gray and white matter on T2-weighted images.

Topics: Abnormalities, Multiple; Adolescent; Adult; Brain; Child; Child, Preschool; Chromosome Deletion; Chromosome Segregation; Chromosomes, Human, Pair 18; Female; Humans; Infant; Intellectual Disability; Magnetic Resonance Imaging; Male; Microsatellite Repeats; Myelin Basic Protein; Phenotype

To study brain MRI findings in patients with 18q- syndrome and to correlate these findings with the results of the molecular breakpoint analysis.. Brain MR images of 17 patients with 18q- syndrome were evaluated. Segregation analysis was performed with 15 microsatellite markers to determine the deletion breakpoints and whether the deletion included the myelin basic protein (MBP) gene.. One patient had an interstitial deletion of 18q which spared the MBP gene. He was the only one with normal brain MRI. All 16 patients with deletions including the MBP gene had abnormal white matter in MRI. The main finding was poor differentiation of gray and white matter on T2-weighted images due to increased white matter signal intensity. In addition, measured signal intensity of the white matter was significantly increased in patients compared with controls.. Poor differentiation of gray and white matter on T2-weighted images is the most typical MRI finding of the 18q- syndrome. These results support the postulation that abnormal myelination in 18q- syndrome is due to haploinsufficiency at or near the MBP locus.

Topics: Abnormalities, Multiple; Adolescent; Adult; Brain; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 18; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Myelin Basic Protein

Magnetic resonance imaging (MRI) and MRI relaxometry were used to investigate disturbed brain myelination in 18q- syndrome, a disorder characterized by mental retardation, dysmorphic features, and growth failure. T1-weighted and dual spin-echo T2-weighted MR images were obtained, and T1 and T2 parametric image maps were created for 20 patients and 12 controls. MRI demonstrated abnormal brain white matter in all patients. White matter T1 and T2 relaxation times were significantly prolonged in patients compared to controls at all ages studied, suggesting incomplete myelination. Chromosome analysis using fluorescence in situ hybridization techniques showed that all patients with abnormal MRI scans and prolonged white matter T1 and T2 relaxation times were missing one copy of the myelin basic protein (MBP) gene. The one patient with normal-appearing white matter and normal white matter T1 and T2 relaxation times possessed two copies of the MBP gene. MRI and molecular genetic data suggest that incomplete cerebral myelination in 18q- is associated with haploinsufficiency of the gene for MBP.

Topics: Abnormalities, Multiple; Adolescent; Brain; Brain Diseases, Metabolic; Child; Child, Preschool; Chromosome Aberrations; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 18; Female; Gene Deletion; Humans; In Situ Hybridization, Fluorescence; Infant; Magnetic Resonance Imaging; Male; Myelin Basic Protein; Myelin Sheath; Polymerase Chain Reaction; Syndrome

Topics: Abnormalities, Multiple; Animals; Chromosome Mapping; Crosses, Genetic; Genes; Humans; Mice; Mice, Inbred C57BL; Muridae; Myelin Basic Protein; Polymorphism, Restriction Fragment Length; Receptors, Galanin; Receptors, Gastrointestinal Hormone; Species Specificity; Syndrome

We report a mother and son with a deletion at 18q22.3. Both have the typical manifestations of the 18q- syndrome. In addition, both have an action tremor which became apparent in childhood. The mother subsequently developed chorea and dysmetria in late adolescence. Magnetic resonance imaging of their brains showed poor myelination of the central white matter tracts with relatively normal myelination of the corpus callosum. We propose that these neurologic findings are most likely due to a failure of expression of the myelin basic protein gene.

Topics: Abnormalities, Multiple; Adult; Brain; Chromosome Deletion; Chromosomes, Human, Pair 18; Ear; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Myelin Basic Protein; Tremor