truncal ataxia

Spinocerebellar Ataxia 37

Clinical Characteristics
Ocular Features: 

 Abnormal ocular movements are common, beginning with dysmetric vertical saccades and irregularities of vertical pursuit, with later development of irregular horizontal tracking movements.  Nystagmus is sometimes present. 

Two otherwise asymptomatic individuals with dysmetric vertical saccades and irregular vertical pursuit movements had normal horizontal pursuit movements at the ages of 32 and 40 years and were found to have the SCA37 haplotype.   

Systemic Features: 

The mean age of onset in is about 50 years with signs of dysarthria and a clumsy gait.  Other more variable findings include truncal ataxia, dysmetria, and sometimes dysphagia.  Slow progression of signs may lead to eventual wheelchair dependence within one or two decades of disease onset.  Brain imaging reveals cerebellar atrophy with sparing of the brainstem.

Genetics

Heterozygous mutations in the DAB1 gene (1p32.2) are responsible for this disorder.   This disorder of adult onset has been described in several families living on the Iberian peninsula.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No effective treatment has been reported.

References
Article Title: 

A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia

Seixas AI, Loureiro JR, Costa C, Ordonez-Ugalde A, Marcelino H, Oliveira CL, Loureiro JL, Dhingra A, Brandao E, Cruz VT, Timoteo A, Quintans B, Rouleau GA, Rizzu P, Carracedo A, Bessa J, Heutink P, Sequeiros J, Sobrido MJ, Coutinho P, Silveira I. A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia. Am J Hum Genet. 2017 Jul 6;101(1):87-103.

PubMed ID: 
28686858

Spastic Ataxia 8, Autosomal Recessive, with Hypomyelinating Leukodystrophy

Clinical Characteristics
Ocular Features: 

Reported ocular signs are limited to abnormal eye movements.  In other forms of spastic ataxia, nystagmus is evident in association with optic atrophy but no fundus examinations are reported in the 3 families with SPAX8.  Hypometric saccades and limited upgaze have also been found in these families.

Systemic Features: 

First signs and symptoms occur sometime in the first 5 years of life and often in the first year.   In 6 of 7 reported patients the presenting sign was nystagmus but one individual with reported onset of disease at age 5 years presented with ataxia.  Cerebellar signs, both truncal and limb, are usually present and the majority of individuals have evidence of dystonia.  Likewise, pyramidal signs are nearly always present.  Cerebellar dysarthria and titubation are often present with dystonic posturing and torticollis. 

Brain MRIs usually reveal cerebellar atrophy and widespread hypomyelination.  Two individuals in a single family had severe global psychomotor delays as well.  No sensory deficits were reported.  This disorder is progressive and patients in adulthood may require the use of a wheelchair.

Genetics

Homozygous mutations in the NKX6-2 (NKX6-2) gene (10q26.3) are responsible for this disorder.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported for the general condition.

References
Article Title: 

Mutations in NKX6-2 Cause Progressive Spastic Ataxia and Hypomyelination

Chelban V, Patel N, Vandrovcova J, Zanetti MN, Lynch DS, Ryten M, Botia JA, Bello O, Tribollet E, Efthymiou S, Davagnanam I; SYNAPSE Study Group, Bashiri FA, Wood NW, Rothman JE, Alkuraya FS, Houlden H. Mutations in NKX6-2 Cause Progressive Spastic Ataxia and Hypomyelination. Am J Hum Genet. 2017 Jun 1;100(6):969-977.

PubMed ID: 
28575651

Spinocerebellar Ataxia 18

Clinical Characteristics
Ocular Features: 

Ocular signs in SCAR18 include nystagmus, oculomotor apraxia, and optic atrophy.  The nystagmus may be rotatory or horizontal and can be gaze-evoked.  Some patients have intermittent and tonic upgaze.  Visual acuity has not been reported.

Systemic Features: 

Patients are developmentally delayed and have intellectual disability.  These features do not seem to be progressive.  Ataxia, both truncal and cerebellar, is present.  Mobility is impaired from early childhood and eventually requires assistance.   Joint contractures sometimes develop and patients can be wheelchair-bound by the second decade.  Dysarthric speech is common.  No dysmorphic facial features are present.

Brain imaging shows progressive cerebellar and sometimes cerebral atrophy.

Genetics

This autosomal recessive disorder results from homozygous deletions in the GRID2 gene (4q22).  This gene codes for a subunit of the glutamate receptor channel and is thought to be selectively expressed in the Purkinje cells of the cerebellum.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment has been reported.  However, physical therapy, assistive devices for mobility, and low vision aids may be helpful.

References
Article Title: 
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