VLDLR-associated cerebellar hypoplasia

Reviewed October 2009

What is VLDLR-associated cerebellar hypoplasia?

VLDLR-associated cerebellar hypoplasia is an inherited condition that affects the development of the brain. People with this condition have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. This brain malformation leads to problems with balance and coordination (ataxia) that become apparent in infancy and remain stable over time. Children with VLDLR-associated cerebellar hypoplasia may learn to walk later in childhood, usually after the age of 6, although some are never able to walk independently. In one Turkish family, affected people walk on their hands and feet (quadrupedal locomotion).

Additional features of VLDLR-associated cerebellar hypoplasia include moderate to profound intellectual disability, impaired speech (dysarthria) or a lack of speech, and eyes that do not look in the same direction (strabismus). Some affected individuals have also had flat feet (pes planus), seizures, and short stature. Studies suggest that VLDLR-associated cerebellar hypoplasia does not significantly affect a person's life expectancy.

How common is VLDLR-associated cerebellar hypoplasia?

VLDLR-associated cerebellar hypoplasia is rare; its prevalence is unknown. The condition was first described in the Hutterite population in Canada and the United States. This condition has also been reported in families from Iran and Turkey.

What genes are related to VLDLR-associated cerebellar hypoplasia?

As its name suggests, VLDLR-associated cerebellar hypoplasia results from mutations in the VLDLR gene. This gene provides instructions for making a protein called a very low density lipoprotein (VLDL) receptor. Starting before birth, this protein plays a critical role in guiding the movement of developing nerve cells to their appropriate locations in the brain. Mutations in the VLDLR gene prevent cells from producing any functional VLDL receptor protein. Without this protein, developing nerve cells cannot reach the parts of the brain where they are needed. The resulting problems with brain development lead to ataxia and the other major features of this condition.

Related Gene(s)

Changes in this gene are associated with VLDLR-associated cerebellar hypoplasia.

VLDLR

How do people inherit VLDLR-associated cerebellar hypoplasia?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of VLDLR-associated cerebellar hypoplasia?

These resources address the diagnosis or management of VLDLR-associated cerebellar hypoplasia and may include treatment providers.

Gene Review: Hereditary Ataxias (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ataxias)
Gene Review: VLDLR-Associated Cerebellar Hypoplasia (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=vldlr-ch)
Gene Tests: VLDLR-Associated Cerebellar Hypoplasia (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/296095)

You might also find information on the diagnosis or management of VLDLR-associated cerebellar hypoplasia in Educational resources (http://ghr.nlm.nih.gov/condition/vldlr-associated-cerebellar-hypoplasia/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/vldlr-associated-cerebellar-hypoplasia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about VLDLR-associated cerebellar hypoplasia?

You may find the following resources about VLDLR-associated cerebellar hypoplasia helpful. These materials are written for the general public.

MedlinePlus - Health information
- Health Topic: Cerebellar Disorders (http://www.nlm.nih.gov/medlineplus/cerebellardisorders.html)
- Health Topic: Movement Disorders (http://www.nlm.nih.gov/medlineplus/movementdisorders.html)
Additional NIH Resources - National Institutes of Health
National Institute of Neurological Disorders and Stroke: Cerebellar Hypoplasia Information Page (http://www.ninds.nih.gov/disorders/cerebellar_hypoplasia/cerebellar_hypoplasia.htm)
Educational resources - Information pages
- Neuromuscular Disease Center, Washington University, St. Louis (http://neuromuscular.wustl.edu/ataxia/recatax.html)
- Orphanet: Cerebellar Hypoplasia (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1398)
Patient support - For patients and families
- Family Village: Ataxia (http://www.familyvillage.wisc.edu/lib_atax.htm)
- National Ataxia Foundation (http://www.ataxia.org/)
- Worldwide Education and Awareness for Movement Disorders (WE MOVE): Ataxia (http://www.wemove.org/ataxia/)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary
- Gene Review: Hereditary Ataxias (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ataxias)
- Gene Review: VLDLR-Associated Cerebellar Hypoplasia (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=vldlr-ch)
Gene Tests - Genetic tests ordered by healthcare professionals (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/296095)
ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?term=%22VLDLR-associated%20cerebellar%20hypoplasia%22%20%5BDISEASE%5D%20OR%20%22Cerebellar%20Ataxia%22%20%5BDISEASE%5D%20OR%20NCT00041600%20%5BID-NUMBER%5D)
PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((cerebellar%20hypoplasia%20%5Btiab%5D%20AND%20VLDLR%20%5Btiab%5D)%20OR%20(dysequilibrium%20syndrome%20%5Btiab%5D%20AND%20VLDLR%20%5Btiab%5D)%20OR%20(cerebellar%20hypoplasia%20%5Btiab%5D%20AND%20very%20low%20density%20lipoprotein%20receptor%20%5Btiab%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/224050)

What other names do people use for VLDLR-associated cerebellar hypoplasia?

autosomal recessive cerebellar ataxia with mental retardation
autosomal recessive cerebellar hypoplasia with cerebral gyral simplification
cerebellar disorder, nonprogressive, with mental retardation
cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion
cerebellar hypoplasia, VLDLR-associated
CHMRQ1
DES-VLDLR
dysequilibrium syndrome-VLDLR
VLDLRCH
VLDLR-CH

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about VLDLR-associated cerebellar hypoplasia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding VLDLR-associated cerebellar hypoplasia?

ataxia ; autosomal ; autosomal recessive ; cell ; cerebellum ; dysarthria ; gene ; hypoplasia ; lipoprotein ; malformation ; mental retardation ; mutation ; nerve cell ; population ; prevalence ; protein ; receptor ; recessive ; seizure ; short stature ; sign ; stature ; strabismus ; symptom ; syndrome ; very low density lipoprotein ; VLDL

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

Boycott KM, Bonnemann C, Herz J, Neuert S, Beaulieu C, Scott JN, Venkatasubramanian A, Parboosingh JS. Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (dysequilibrium syndrome). J Child Neurol. 2009 Oct;24(10):1310-5. doi: 10.1177/0883073809332696. Epub 2009 Mar 30. (http://www.ncbi.nlm.nih.gov/pubmed/19332571?dopt=Abstract)
Boycott KM, Flavelle S, Bureau A, Glass HC, Fujiwara TM, Wirrell E, Davey K, Chudley AE, Scott JN, McLeod DR, Parboosingh JS. Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification. Am J Hum Genet. 2005 Sep;77(3):477-83. Epub 2005 Jul 22. (http://www.ncbi.nlm.nih.gov/pubmed/16080122?dopt=Abstract)
Gene Review: VLDLR-Associated Cerebellar Hypoplasia (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=vldlr-ch)
Moheb LA, Tzschach A, Garshasbi M, Kahrizi K, Darvish H, Heshmati Y, Kordi A, Najmabadi H, Ropers HH, Kuss AW. Identification of a nonsense mutation in the very low-density lipoprotein receptor gene (VLDLR) in an Iranian family with dysequilibrium syndrome. Eur J Hum Genet. 2008 Feb;16(2):270-3. Epub 2007 Nov 28. (http://www.ncbi.nlm.nih.gov/pubmed/18043714?dopt=Abstract)
Ozcelik T, Akarsu N, Uz E, Caglayan S, Gulsuner S, Onat OE, Tan M, Tan U. Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4232-6. doi: 10.1073/pnas.0710010105. Epub 2008 Mar 7. (http://www.ncbi.nlm.nih.gov/pubmed/18326629?dopt=Abstract)
Türkmen S, Hoffmann K, Demirhan O, Aruoba D, Humphrey N, Mundlos S. Cerebellar hypoplasia, with quadrupedal locomotion, caused by mutations in the very low-density lipoprotein receptor gene. Eur J Hum Genet. 2008 Sep;16(9):1070-4. doi: 10.1038/ejhg.2008.73. Epub 2008 Mar 26. (http://www.ncbi.nlm.nih.gov/pubmed/18364738?dopt=Abstract)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.



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