Protocol Number: 09-HG-0128

Title:

Leukodystrophies of Unknown Cause

Number:

09-HG-0128

Summary:

Genetic white matter disorders (leukodystrophies) are estimated to have an incidence of 1:5000 live births. As many as 50% of patients with white matter disease remain undiagnosed after conventional neuroimaging, biochemical and genetic testing, and therefore have unclassified leukodystrophies. Moreover, the mechanisms of disease in many leukodystrophies of known cause are very poorly understood: many are systemic abnormalities that manifest only in white matter. The purpose of this study is to: (a) define novel homogeneous groups of patients with leukodystrophy and work toward finding the cause of these disorders and (b) establish disease mechanisms in selected classified leukodystrophies. In order to achieve these goals, patients with leukodystrophy will be analyzed by clinical, neurophysiological, biochemical and genetic means. For goal (a), patients would have been diagnosed as having an unclassified leukodystrophy or no known cause of their leukodystrophy at outside centers. At the Clinical Center, such patients will undergo a series of neuropsychological, blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. Some of these tests will be part of a standard battery while others will be tailored to individual patients. For goal (b), selected leukodystrophies with a defined genetic cause will be selected for further mechanistic study, using clinical and laboratory tools to establish increased understanding of the underlying pathophysiology. It is hoped that the present study will help clarify the nosology of the leukodystrophies and significantly advance our understanding of the pathogenesis of these diseases.

Sponsoring Institute:

National Human Genome Research Institute (NHGRI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

- Patients with white matter disease that is unclassified or of unknown cause, including, but not limited to leukoencephalopathies with calcifications, leukoencephalopathies with cysts, leukoencephalopathies with hypomyelination and leukoencephalopathies with brainstem involvement.

- Parents or siblings of these subjects

EXCLUSION CRITERIA:

-Patients meeting above criteria but too ill to travel to the clinical center. In that case, consideration will be given to enrolling them for the collection of medical records and samples only.

-Patients meeting above criteria, but where the leukoencephalopathy is felt to be secondary to an acquired cause, for example traumatic, or infectious.

Special Instructions:

Currently Not Provided

Keywords:

Genetic Disorder

White Matter

Leukodystrophies

Myelin

Recruitment Keyword(s):

None

Condition(s):

Myelin Sheath

Leukodystrophy

Leukoencephalopathy

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Human Genome Research Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Linnankivi TT, Autti TH, Pihko SH, Somer MS, Tienari PJ, Wirtavuori KO, Valanne LK.18q-syndrome: brain MRI shows poor differentiation of gray and white matter on T2-weighted images. J Magn Reson Imaging. 2003 Oct;18(4):414-9.

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, Fox PT. Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency. Am J Med Genet. 1997 Jul 25;74(4):422-31.

Ugur SA, Tolun A.A deletion in DRCTNNB1A associated with hypomyelination and juvenile onset cataract. Eur J Hum Genet. 2008 Feb;16(2):261-4. Epub 2007 Oct 10.

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