HUT (Hutterite)

Inheritance: autosomal recessive
Genes: VLDLR

Disequilibrium syndrome
DES
Cerebellar disorder with mental retardation

Cerebellar ataxia
Mental retardation
Hypoplasia of the inferior cerebellum
Hypotonia
Unsteadiness
Delayed motor development
Seizures
Tremors
Spasticity

Cerebellar Hypoplasia (VLDR-associated)

Clinical Characteristics

General description (for patients):  

Delayed development in motor functions is evident in the first year of life.  Unsteadiness may delay unassisted walking for 5 to 20 years.  The condition is usually nonprogressive.  Speech may also be abnormal, seizures are often present, and many patients have more widespread brain dysfunction with mental retardation. Individuals can be short in stature as well.


Medical description: 

Abnormal neuroblast migration during development results in nonprogressive cerebral and cerebellar signs including severe ataxia, mental retardation, speech and motor retardation, and often seizures.  Short stature is seen in 15% but intention tremors and athetoid posturing are more common.  MRI shows inferior cerebellar hypoplasia and simplification of the cortical gyri.


Genetics:   

Among eight patients from three related Hutterite famiies, a 199 base pair deletion was found in the VLDLR gene on chromosome 9 (9p24).   VLDLR encodes the very low density lipoprotein receptor, and is part of a signaling pathway which directs the migration of neuroblasts in the cerebral cortex and cerebellum.  Homozygosity of the deletion in these patients and the relationship of their Hutterite parents suggest autosomal recessive inheritance.

Treatment:  

No treatment is available.

Prognosis:  

This is a nonlethal condition although severe disability is present.

Ancillary treatments and support:  

General supportive care.  Physical therapy and mobility training may be useful.

Specialists and specialty centers:

Physical therapists, neurologist.

References:

Boycott, K.M., Flavelle, S., Bureau, A., Glass, H.C., Fujivara, T.M., Wirrell, E., Davey, K, Chudley, A.E., Scott, J.N., McLeod, D.R., and Parboosigh, J.S.:  Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification.  Am. J. Hum. Genet. 77: 477-483, 2004.  PubMed ID: 16080122

Schurig, V., Orman, A.V., and Bowen, P.:   Nonprogressive cerebellar disorder with mental retardation and autosomal recessive inheritance in Hutterites.  Am. J. Med. Genet. 9: 43-53, 1981.  PubMed ID: 7246619

Pallister, P.D., and Opitz, J.M.:  Disequilibrium syndrome in Montana Hutterites.  Am. J. Med. Genet. 22: 569-569, 1985. PubMed ID: 4061489

Resources:

NINDS Cerebellar Hypoplasia Information Page


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