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Official Journal of the European Paediatric Neurology Society

Case study

Early onset autosomal dominant spinocerebellar ataxiawith miosis: Four cases

Niklas Timbya,�, Eva-Lena Stattinb, Ingela Kristiansenc, Urban Erikssonc, Anders Eriksona

aDepartment of Pediatrics, Umea University Hospital, SwedenbDepartment of Clinical Genetics, Umea University Hospital, SwedencPediatric Clinic, Ostersund Hospital, Sweden

a r t i c l e i n f o

Article history:

Received 11 January 2007

Received in revised form

15 February 2007

Accepted 6 March 2007

Keywords:

Spinocerebellar ataxia (SCA)

Autosomal dominant

Miosis

Hyperreflexia

nt matter & 2007 Europe07.03.007

hor. Tel.: +46 907850000; fiklas.timby@vll.se (N. Ti

a b s t r a c t

Previously, at least 29 different forms of autosomal dominant spinocerebellar ataxias

(SCAs) have been described. We describe a family with four members through three

generations with autosomal dominant ataxia in combination with miosis and hyperre-

flexia. This family’s ataxia does not match any of the previously described SCAs and is

probably a novel form of SCA. To continue with the search for the genetic background of

this disease, more cases are needed.

& 2007 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

1. Introduction

Autosomal dominant cerebellar ataxias have been organized

according to their genetic basis of disease, and are termed

spinocerebellar ataxias (SCAs). At least 29 different forms of

SCAs have been described so far.1 The SCAs are named in

order after their gene description (SCA 1–28) except for

dentatorubral pallidoluysian atrophy (DRPLA). Additional

neurological and psychiatric symptoms as well as age at

onset and progressiveness are often overlapping but

every SCA has still its own phenotypic description. Six SCAs

(SCA 1–3, 6–7, 17) and DRPLA are known to be caused by

cytosine-adenine-guanine (CAG) trinucleotide repeat expan-

sions in the coding region of the mutated gene leading to

abnormally long polyglutamine stretches in the protein.

Anticipation, a phenomenon where an earlier age at onset

an Paediatric Neurology

ax: +46 90123728.mby).

and a more severe progression of disease is seen in successive

generations, is associated with disorders due to expanded

CAG repeats. Ataxia and dysarthria are present in all forms of

SCA. Eye symptoms (nystagmus, slow saccades, ophtalmo-

plegia, retinopathy), pyramidal (hyper- and hyporeflexia,

spasticity) and extrapyramidal (tremor, bradykinesia) signs,

dementia, executive dysfunction, and peripheral neuropathy

are additional symptoms present in one or several SCAs.2,3

2. Case study

The family whose pedigree is shown in Fig. 1 was identified.

The four afflicted family members were examined by one

examiner (NT), and data from earlier hospital visits were

obtained.

Society. Published by Elsevier Ltd. All rights reserved.

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I:1 I:2

II:1 II:2 II:3 II:5 II:6II:4

III:2 III:4III:3III:1

IV:1

I

II

III

IV

Fig. 1 – Family pedigree.

E UR O P EA N J O UR NA L O F PA ED I ATR I C N E U RO L O G Y 12 (2008) 38 – 40 39

2.1. Case IV:1

Girl, 412 years old. Born slightly preterm (w36+5) with no

perinatal complications. By the age of 1 year and 2 months

she was referred to hospital from the child welfare clinic

because of instability when sitting. She was able to walk

unaided by the age of 2. Already between 2 and 3 years of age,

her walking was described as ataxic. MRI of the brain at 312

years was normal and eye examination at 412 years showed no

pathological changes of the retina. When examining her at

the age of 412 years she has an obvious ataxic gait, trunk ataxia

and she cannot close her eyes when standing without falling.

Finger-nose and dysdiadokokinesis are poor and her deep

tendon reflexes are brisk, both in upper and lower extremi-

ties. Eye movements are normal and no nystagmus can be

seen. Further, her pupils are miotic and are not widened in

dark.

2.2. Case III:2

Man, 27 years, father of case IV:1. He was referred to hospital

by the age of 212 years. No history of perinatal complications.

A non-symptomatic valvular stenosis of the pulmonary artery

was found, but needed no treatment. At 212 years of age, his

ataxia was obvious, especially in trunk and legs. He could

walk unaided by the age of 2, and ride a bicycle by the age of 7.

At 16 years of age, bilateral miosis was observed. His

education was 9 years at comprehensive school and 2 years

at college of forestry, and he is now working with forestry. His

ataxia has not shown any progression and he has learnt to

adapt to his balance problems. The ataxia is worsened by

fatigue and in dark. On examination at 27 years of age, he has

an ataxic gait. He cannot stand on his left foot alone (but can

stand on his right foot with some problems). He does small

failures in finger–nose and heel–knee tests. His speech reveals

a mild dysarthria. Deep tendon reflexes in the legs are brisk,

in the arms normal and plantar responses are flexor. The

pupils are miotic and do not dilate in the dark. No abnormal

eye movements are observed. When his daughter showed

signs of ataxia, genetic testing was made for SCA 1–3 and SCA

6–8, all negative.

2.3. Case III:4

Man aged 26, brother of case III:2. No history of neonatal

complications. He was referred to hospital at 2 years and 3

months, which was at the same time he started to walk

independently. At that age he showed signs of ataxia,

especially when handling objects with his hands. It was also

noticed that his reflexes were brisk. By the age of 7, he had

developed bilateral miosis. As for his brother, the ataxia has

not been progressive and is worsened by fatigue. He has

found out that his balance problems are improving by small

amounts of alcohol. After 9 years at comprehensive school

and 4 years at secondary school, he is now working as a lorry

driver. On examination at 26 years of age, he shows, like his

brother, an ataxic gait, difficulties in finger–nose and knee–

heel tests, a mild dysarthria and bilateral miotic pupils not

widened in the dark. Deep tendon reflexes in the legs are

brisk, in the arms normal. Plantar responses are flexor.

2.4. Case II:5

Woman, aged 61, mother of cases III:2 and III:4. She suffered

from balance problems during childhood, problems that have

been consistent through her life. She has never been referred

to hospital for her balance problems. She could walk by the

age of 3, but has never learnt to ride a bicycle. The older

she gets, the more she has learnt to adapt her life to her

balance problems. When she moves slowly, her ataxia is less

obvious, and when fatigued or under stress, the problems are

worsened. She has suffered from depression in adulthood.

When examining her at 61 years of age, she has ataxia of

about the same degree as her sons. Her speech is mildly

dysarthric, and she also has small pupils that do not dilate in

the dark. Her reflexes in the legs are brisk, in the arms

normal. Plantar responses are flexor.

2.5. Deceased and unaffected family members

Case II:5 is the first case in the family. Both her parents

(I:1 and I:2) and her only brother (II:1) are deceased. None of

them had balance problems. All of her sisters (II:2, II:3, II:6),

51–55 years old, and her only daughter (III:3), 35 years old, are

also unaffected with no balance problems.

3. Discussion

We describe four patients in a family with an autosomal

dominant ataxia. Additional symptoms are bilateral miosis

and hyperreflexia, especially in the lower limbs. The ataxia is

present from the first years of life, seems not to be

progressive, and shows no obvious anticipation. The miosis

is not present from birth, but starts by the age of 4–16.

Inherited ataxia combined with pupil anomaly without

retinal changes is seldom described in literature. In 1892, Dr

Sanger Brown described 21 patients through four generations

with inherited ataxia and pyramidal symptoms. Three of

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these patients had pathological pupil reaction to light, but

none were described as having miosis.4 The only description

of inherited ataxia combined with miosis we could find is a

case report of a mother and three of her five children in the

age of 44, 25, 24 and 17 who all had a spastic ataxia with

bilateral miosis. The ataxia was present from early life and

not progressive. All four had bilateral miosis and nystagmus.5

None of the 29 SCAs previously described have miosis as an

additional symptom.3 The miosis in our four cases is so

obvious, so it is not likely that it would not have been

mentioned if present in any of the thoroughly made

investigations of the previously described SCAs. We believe

that the family we present, has a previously unknown form of

SCA where miosis and hyperreflexia are additional symp-

toms. The family described by Dick et al. before the genomic

era5 had probably a similar defect as the patients in the

present family, even though their miosis was congenital and

the nystagmus noted in those patients is absent in our family.

Genetic examination with genome wide scan to elucidate the

genetic background of the disease would be the next step in

understanding this disease and its correlation with other

SCAs. Our own sample of four patients is too small though,

and we hope to make contact with colleagues who have

patients with a similar clinical picture to co-operate and

make it possible to continue with the genetic search.

Acknowledgements

This report was supported by grants from Vasterbotten

County Council (ALF).

R E F E R E N C E S

1. Morrison PJ. Gene table: paediatric and adult ataxias (update 5).Eur J Ped Neurol 2006;10:249–53.

2. Duenas AM, Goold R, Giunti P. Molecular pathogenesis ofspinocerebellar ataxias. Brain 2006;129:1357–70.

3. Schols L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomaldominant cerebellar ataxias: clinical features, genetics, andpathogenesis. Lancet Neurol 2004;3:291–304.

4. Brown S. On hereditary ataxia with a series of twenty-onecases. Brain 1892;15:250–68.

5. Dick DJ, Newman PK, Cleland PG. Hereditary spastic ataxiawith congenital miosis: four cases in one family. Brit J Ophtal1983;67:97–101.