G2Cdb::Human Disease report

Disease id
D00000317
Name
18q-syndrome
Nervous system disease
yes

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001807 MBP
myelin basic protein
Y (1383862) Deletion (D) Y
G00001807 MBP
myelin basic protein
Y (1700607) Deletion (D) Y
G00001807 MBP
myelin basic protein
Y (8728701) Deletion (D) N
G00001807 MBP
myelin basic protein
Y (8767586) Deletion (D) Y
G00001807 MBP
myelin basic protein
Y (8933867) Deletion (D) ?
G00001807 MBP
myelin basic protein
Y (9259379) Deletion (D) Y
G00001807 MBP
myelin basic protein
Y (14508777) Deletion (D) Y

References

  • 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images.

    Linnankivi TT, Autti TH, Pihko SH, Somer MS, Tienari PJ, Wirtavuori KO and Valanne LK

    Department of Pediatric Neurology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. tarja.linnankivi@hus.fi

    Purpose: 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.

    Results: 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.

    Conclusions: 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.

    Journal of magnetic resonance imaging : JMRI 2003;18;4;414-9

  • Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency.

    Gay CT, Hardies LJ, Rauch RA, Lancaster JL, Plaetke R, DuPont BR, Cody JD, Cornell JE, Herndon RC, Ghidoni PD, Schiff JM, Kaye CI, Leach RJ and Fox PT

    Department of Pediatrics, University of Texas Health Science Center at San Antonio, 78284, USA.

    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.

    American journal of medical genetics 1997;74;4;422-31

  • White matter changes associated with deletions of the long arm of chromosome 18 (18q- syndrome): a dysmyelinating disorder?

    Loevner LA, Shapiro RM, Grossman RI, Overhauser J and Kamholz J

    Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.

    Purpose: To evaluate the MR findings in the central nervous systems of patients with deletions of the long arm of chromosome 18 (18q- syndrome).

    Methods: Sixteen patients with 18q- syndrome ranging in age from 3 to 46 years (mean, 17 years) were studied with high-field-strength MR imaging. Images were analyzed for abnormal T2 hyperintensity in the white matter, abnormal T2 hypointensity in the deep gray matter, and atrophy.

    Results: Ten of 16 patients had abnormal white matter. Diffuse, bilaterally symmetric deep white matter T2 hyperintensity, most pronounced in the periventricular regions, was most common, noted in eight cases. Focal deep white matter lesions and/or abnormalities involving the subcortical white matter were also noted in four cases. The cerebellum, brain stem, and corpus callosum were spared. Ventriculomegally associated with volume loss, and abnormal T2 hypointensity in the basal ganglia and/or thalami were each present in 11 patients.

    Conclusions: The 18q- syndrome is associated with white matter disease and abnormal T2 hypointensity in the deep gray matter. The basis for the white matter abnormalities is unknown, but may be related to one of the two genes for myelin basic protein included in the deleted segment of chromosome 18.

    Funded by: NINDS NIH HHS: R01 NS2 9029-01A1

    AJNR. American journal of neuroradiology 1996;17;10;1843-8

  • A new deletion of 18q23 with few typical features of the 18q- syndrome.

    Kohonen-Corish M, Strathdee G, Overhauser J, McDonald T and Jammu V

    Division of Molecular Medicine, Australian National University, Canberra.

    We report on a patient with a deletion of 18q23. At both 2 and 4 years of age, she displayed few of the facial features or other clinical features associated with the 18q- syndrome. Fluorescent in situ hybridisation and microsatellite marker and RFLP analysis were performed to characterise the extent of the deletion, and a terminal deletion of 18q23 was confirmed. The deleted region includes the gene for myelin basic protein, suggesting that hemizygosity of this gene does not invariably lead to mental and developmental delay. The clinical presentation of this patient suggests that either she is not deleted for the genes involved in the 18q- clinical phenotype or this patient represents one end of the spectrum of the clinical variability seen with 18q terminal deletions.

    Journal of medical genetics 1996;33;3;240-3

  • [18q syndrome with deficiency of myelin basic protein (MBP)].

    Iester A, Vignola S, Callegarini L, Gimelli G and Alpigiani MG

    1a Clinica Pediatrica dell'Università, Istituto G. Gaslini di Genova, Italia.

    The Authors present a patient with 18q- Syndrome in which lymphatic cell karyotype could resume development of extrapyramidal degeneration signs before they appeared. Severity range of phenotypic manifestations in the 18q- syndrome is correlated with chromosomic breakpoint and with genetic background. Many chromosome 18's distal arm genes have been mapped Myelin Basic Protein gene (MBP) has been located in 22-23 position; it forms about 30-40% of myelinic sheath proteins. Failure in MBP gene expression would be correlated in the central white matter with extrapyramidal system degeneration signs: in 18q- patients with involuntary movements studied by MRI or by post-mortem autopsy unmyelinated areas in central white matter tracts have been put in evidence. As MBP absence in peripheral nervous system does not appear to have a functional effect, it has been suggested that some specific component of peripheral myelin is functionally equivalent to MBP and capable to substitute this protein in its absence.

    La Pediatria medica e chirurgica : Medical and surgical pediatrics 1996;18;2;201-5

  • A study of evoked potentials in the 18q-syndrome which includes the absence of the gene locus for myelin basic protein.

    Rodichok L and Miller G

    Department of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey.

    We report evoked potential findings in a patient with 18q-syndrome (18q22.3----qter). The deletion included the locus for myelin basic protein (MBP). Clinical manifestations were mild intellectual deficit, involuntary movements and ataxia. MRI of the brain showed diffusely abnormal white matter. Visual evoked responses were normal. Central conduction was prolonged on median somatosensory evoked potentials and no central response was seen with posterior tibial somatosensory potentials. Putative congenital deficiency of MBP does not necessarily cause abnormal visual evoked responses.

    Neuropediatrics 1992;23;4;218-20

  • Neurologic manifestations in 18q- syndrome.

    Miller G, Mowrey PN, Hopper KD, Frankel CA and Ladda RL

    Department of Pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.

    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.

    American journal of medical genetics 1990;37;1;128-32

Literature (7)

Pubmed - human_disease

  • 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images.

    Linnankivi TT, Autti TH, Pihko SH, Somer MS, Tienari PJ, Wirtavuori KO and Valanne LK

    Department of Pediatric Neurology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. tarja.linnankivi@hus.fi

    Purpose: 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.

    Results: 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.

    Conclusions: 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.

    Journal of magnetic resonance imaging : JMRI 2003;18;4;414-9

  • Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency.

    Gay CT, Hardies LJ, Rauch RA, Lancaster JL, Plaetke R, DuPont BR, Cody JD, Cornell JE, Herndon RC, Ghidoni PD, Schiff JM, Kaye CI, Leach RJ and Fox PT

    Department of Pediatrics, University of Texas Health Science Center at San Antonio, 78284, USA.

    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.

    American journal of medical genetics 1997;74;4;422-31

  • White matter changes associated with deletions of the long arm of chromosome 18 (18q- syndrome): a dysmyelinating disorder?

    Loevner LA, Shapiro RM, Grossman RI, Overhauser J and Kamholz J

    Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.

    Purpose: To evaluate the MR findings in the central nervous systems of patients with deletions of the long arm of chromosome 18 (18q- syndrome).

    Methods: Sixteen patients with 18q- syndrome ranging in age from 3 to 46 years (mean, 17 years) were studied with high-field-strength MR imaging. Images were analyzed for abnormal T2 hyperintensity in the white matter, abnormal T2 hypointensity in the deep gray matter, and atrophy.

    Results: Ten of 16 patients had abnormal white matter. Diffuse, bilaterally symmetric deep white matter T2 hyperintensity, most pronounced in the periventricular regions, was most common, noted in eight cases. Focal deep white matter lesions and/or abnormalities involving the subcortical white matter were also noted in four cases. The cerebellum, brain stem, and corpus callosum were spared. Ventriculomegally associated with volume loss, and abnormal T2 hypointensity in the basal ganglia and/or thalami were each present in 11 patients.

    Conclusions: The 18q- syndrome is associated with white matter disease and abnormal T2 hypointensity in the deep gray matter. The basis for the white matter abnormalities is unknown, but may be related to one of the two genes for myelin basic protein included in the deleted segment of chromosome 18.

    Funded by: NINDS NIH HHS: R01 NS2 9029-01A1

    AJNR. American journal of neuroradiology 1996;17;10;1843-8

  • A new deletion of 18q23 with few typical features of the 18q- syndrome.

    Kohonen-Corish M, Strathdee G, Overhauser J, McDonald T and Jammu V

    Division of Molecular Medicine, Australian National University, Canberra.

    We report on a patient with a deletion of 18q23. At both 2 and 4 years of age, she displayed few of the facial features or other clinical features associated with the 18q- syndrome. Fluorescent in situ hybridisation and microsatellite marker and RFLP analysis were performed to characterise the extent of the deletion, and a terminal deletion of 18q23 was confirmed. The deleted region includes the gene for myelin basic protein, suggesting that hemizygosity of this gene does not invariably lead to mental and developmental delay. The clinical presentation of this patient suggests that either she is not deleted for the genes involved in the 18q- clinical phenotype or this patient represents one end of the spectrum of the clinical variability seen with 18q terminal deletions.

    Journal of medical genetics 1996;33;3;240-3

  • [18q syndrome with deficiency of myelin basic protein (MBP)].

    Iester A, Vignola S, Callegarini L, Gimelli G and Alpigiani MG

    1a Clinica Pediatrica dell'Università, Istituto G. Gaslini di Genova, Italia.

    The Authors present a patient with 18q- Syndrome in which lymphatic cell karyotype could resume development of extrapyramidal degeneration signs before they appeared. Severity range of phenotypic manifestations in the 18q- syndrome is correlated with chromosomic breakpoint and with genetic background. Many chromosome 18's distal arm genes have been mapped Myelin Basic Protein gene (MBP) has been located in 22-23 position; it forms about 30-40% of myelinic sheath proteins. Failure in MBP gene expression would be correlated in the central white matter with extrapyramidal system degeneration signs: in 18q- patients with involuntary movements studied by MRI or by post-mortem autopsy unmyelinated areas in central white matter tracts have been put in evidence. As MBP absence in peripheral nervous system does not appear to have a functional effect, it has been suggested that some specific component of peripheral myelin is functionally equivalent to MBP and capable to substitute this protein in its absence.

    La Pediatria medica e chirurgica : Medical and surgical pediatrics 1996;18;2;201-5

  • A study of evoked potentials in the 18q-syndrome which includes the absence of the gene locus for myelin basic protein.

    Rodichok L and Miller G

    Department of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey.

    We report evoked potential findings in a patient with 18q-syndrome (18q22.3----qter). The deletion included the locus for myelin basic protein (MBP). Clinical manifestations were mild intellectual deficit, involuntary movements and ataxia. MRI of the brain showed diffusely abnormal white matter. Visual evoked responses were normal. Central conduction was prolonged on median somatosensory evoked potentials and no central response was seen with posterior tibial somatosensory potentials. Putative congenital deficiency of MBP does not necessarily cause abnormal visual evoked responses.

    Neuropediatrics 1992;23;4;218-20

  • Neurologic manifestations in 18q- syndrome.

    Miller G, Mowrey PN, Hopper KD, Frankel CA and Ladda RL

    Department of Pediatrics, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.

    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.

    American journal of medical genetics 1990;37;1;128-32

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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