Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:206-213

Retinitis pigmentosa, ataxia, and peripheralneuropathyRR TUCK, JG McLEOD

From the Department ofMedicine, University ofSydney, Australia

SUMMARY The clinical features of four patients with retinitis pigmentosa, ataxia and peripheralneuropathy but with no increase in serum phytanic acid are reported. Three patients also hadsensorineural deafness and radiological evidence of cerebellar atrophy. Nerve conduction studiesrevealed abnormalities of sensory conduction and normal or only mild slowing of motor conduc-tion velocity. Sural nerve biopsy demonstrated a reduction in the density of myelinated fibres.There were no onion bulb formations. These cases clinically resemble Refsum's disease, butdiffer in having no detectable biochemical abnormality, and a peripheral neuropathy which is nothypertrophic in type. They may represent unusual cases of spinocerebellar degeneration.

Retinitis pigmentosa occurs infrequently as an iso-lated finding in otherwise healthy individuals andfamilies. Its association with deafness, with or with-out other neurological abnormalities is much lesscommon but nevertheless well recognised.1 Inheredopathia atactica polyneuritiformis (Refsum'sdisease), abetalipoproteinaemia, and the Keams-Sayre syndrome, retinitis pigmentosa is associatedwith ataxia, peripheral neuropathy and deafness,and a specific biochemical or histochemical abnor-mality. In the present paper we describe the clinicaland electrophysiological features of four patientswith these signs but no detectable biochemicalabnormality.

Case histories

The main clinical features of the patients are summarisedin table 1.

Case 1 (RPAH 45 30 26)A Maltese farm worker, aged 24 years, presented withunsteadiness of gait, loss of balance and poor vision whichwas first noticed when he was aged 6 years. His visualsymptoms had become worse recently in that he was hav-ing difficulty reading and seeing in the dark. He had noother symptoms. His parents, who were unrelated, had nohistory of neurological disease, nor did his sister or twobrothers. On examination, he was alert but IQ was 54

Address for reprint requests: Dr JG McLeod, Department ofMedicine, University of Sydney,- Sydney, NSW 2006, Australia.

Received 21 July 1982 and in revised form 14 October 1982Accepted 20 October 1982

(WAIS). He had a speech impediment but was not dysar-thric. He was of short stature, had a small head and pescavus but no kyphoscoliosis. His visual acuity in the righteye was 6/60 while in the left he could count fingers only.The right visual field was constricted but the left could notbe tested. The optic discs were pale, the retinal vesselssmall in diameter and throughout the retinae there wasscattered "bone corpuscle" pigmentation. The pupils weresmall and reacted poorly to light and accommodation.There was no ptosis and extraocular movements were full.The remaining cranial nerves were normal. There was nowasting in the limbs and tone and power were normal.There was no intention tremor in the upper limbs but rapidalternating movements were clumsy. Heel-knee-shin test-ing and heel-toe walking were unsteady and his gait waswide-based and ataxic. The upper limb reflexes were nor-mal; the knee jerks could be elicited only with reinforce-ment and the ankle jerks were absent. Both plantarresponses were extensor. There was no sensory loss. Gen-eral examination was normal. On audiometry, there washigh frequency sensorineural loss bilaterally, more severeon the right.The patient was reviewed 4 years later when aged 28.

His visual acuity was unchanged in the right eye but hecould only just perceive light and bilateral cataracts werepresent. Extraocular movements were full and there wasno ptosis. His hearing had deteriorated. There was nowwasting of the small muscles of the feet; appreciation oflight touch and pin prick was diminished on the feet; jointposition sense was abnormal in the fingers and toes andtwo-point discrimination was impaired on the fingers andfeet. Other physical signs were unchanged.

Case 2 (RPHA 35 46 15)A man aged 22 years was referred for investigation ofprogressive deterioration of his balance for 7 years, paraes-thesiae in his feet for 4 years and numbness in the tips of

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Table 1 Summary ofclinical features

Patient Age (yr) Ocular signs Motor Sensation Reflexes Other findings CSF Neuro-examination protein gil radiological

Onset Biopsy Final findingsreview

1 6 24 28 Retinitis pig- Wasted foot Impairment of Diminished Low intelligence 0-99 CT scan: enlargedmentosa muscles pinprick, light KJs Small head vallecula and IVthOptic atrophy Ataxia touch, joint Absent AJs Short stature ventricle,Cataracts position and 2- Extensor Partial deafness suggestive ofVAR: 6/60 point discrim- plantar cerebellarVAL: CF ination responses atrophyConstrictedvisual fieldsPoorly reactingpupils

2 6 22 - Retinitis pig- Intention All modalities All reflexes Short distal 0-27mentosa tremor impaired absent. phalangesVAR: 6/36 Ataxia Flexor plantarVAR: 6/36 responsesConstrictedvisual fieldsNystagmus

3 41 48 50 Retinitis pig- Intention Impaired pin- Absent BJs Dry skin on 0-29 CT scan: largementosa tremor prick, vibra- SJs, AJs lower limbs IVth ventricleVAR: 6/24 Ataxia tion & 2-point Flexor Partial and cerebellarVAL: 6/18 Slight discrimination plantar deafness atrophyConstricted wasting of responsesvisual fields intrinsicNystagmus hand muscles

4 48 60 70 Retinitis pig- Intention Impaired pin- Normal Mild sensori- 0-40 PEG: cerebellarmentosa tremor prick and flexor neural deafness atrophyCataracts Ataxia vibration plantarVAR: CF Slight wast- responsesVAL: CF ing of intrinsic(totally blind hand muscleson review)

VA: visual acuity; CF = able to count fingers only; BJ = biceps jerk; SJ = supinator; KJ = knee jerk; AJ = ankle jerk; PEG = pneumoencephalogram.

his fingers for 2 years. From the age of 6 years he hadnoticed a reduction in his peripheral vision and difficultyseeing at night. He had noticed no loss of hearing but hadexperienced some tinnitus 2 years ago. He was born inSicily of unrelated parents and had two brothers and twosisters who were all apparently in good health. He did notwork. On examination, he had short distal phalanges withthickened skin but he was of otherwise normal build withno scoliosis nor pes cavus. He did not have a rash orichthyosis. His sense of smell was intact. Corrected visualacuity was 6/36 in each eye and the visual fields were con-stricted. Retinitis pigmentosa was present in the peripheryof both fundi. The optic discs were normal. Extraocularmovements were full and bilateral horizontal nystagmuswas present. There was no ptosis, and the pupils reactednormally to light and accommodation. There was no deaf-ness. The cranial nerves were otherwise normal. There wasno wasting and power and tone were normal in the upperand lower limbs. In the upper limbs there was a mild inten-tion tremor and impairment of rapid altemating move-ments. His performance of the heel-knee-shin test wasimpaired, his gait was ataxic and Romberg's sign was posi-tive. Deep tendon reflexes were absent and plantarresponses flexor. Appreciation of light touch and pin-prickwere impaired below the elbows and knees; vibration sensewas absent below the elbows and iliac crests; joint position

sense was impaired in the fingers and toes. Two point dis-crimination was greater than 5 mm in the fingers and 6 cmin the feet. The peripheral nerves were not enlarged andthe general examination was normal. Pure tone audiogramwas normal.

Case 3 (RPAH 56 03 37)For 7 years this policeman aged 48 years noticed progres-sive unsteadiness of gait, deteriorating vision and deafness.He had no difficulty reading but his night vision was poorand he could not see objects outside of his direction ofgaze. He did not drink alcohol and ceased smoking in1976. His parents were unrelated and there was no familyhistory of visual failure nor of progressive neurological ill-ness. On examination he was obese. There was no kyphos-coliosis, pes cavus nor peripheral nerve enlargement. Hissense of smell was normal. Corrected visual acuity was6/24 in the right eye and 6/18 in the left. The visual fieldswere markedly constricted and there was bilateral retinitispigmentosa with normal optic discs. The pupils reactednormally to light and accommodation. There was no ptosis.Extraocular movements were full but there was bilateralhorizontal nystagmus. He could not hear the whisperedword and often missed normal conversation. Air conduc-tion was better than bone conduction. The remainder ofthe cranial nerves was intact. There was slight wasting of

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Table 2 Results ofnerve conduction studies

Tuck, McLeod

Patient Motor conduction velocity (mls) Sensory action potentials

Age Median Ulnar Lateral Median nerve Ulnar nerve Sural nerveSex nerve nerve popliteal

Latency Amplitude Latency Amplitude Latency Amplitude(ms) (AV) (ms) (Axv) (ms) (,uv)

1 M24 50 50 37 3-2 6 2-3 5 NR NR2 M22 66 57 43 - 0 - 0 - 03 M48 50 56 45 3-0 14 - 0 NR NR4 M60 56 43 36 3-3 10 3-2 5 4-2 3Controlrange2 18-73 50-66 47-69 41-56 24-3-2 11-40 2-1-3.1 7-36

(NR = No recording attempted).

interossei in the hands but there was no weakness. Tonewas decreased in upper and lower limbs. Rapid alternatinghand movements were normal but there was an intentiontremor and heel-knee-shin test was impaired. The tricepsand knee jerks were present but biceps, supinator andankle jerks were absent. Plantar responses were flexor.The sensory examination in the upper limbs was normal.Appreciation of light touch and joint position were normalin the lower limbs but pain-sensation was absent below theknees and vibration sense was absent in the toes. Twopoint discrimination was greater than 10 cm on the feet.His gait was ataxic and wide based and Romberg's sign waspositive. General examination was normal apart fromsmall testes and dry skin on the legs. An audiogramrevealed bilateral severe sensorineural hearing loss.When reviewed two years later, he complained that his

peripheral vision, balance and hearing had deterioratedslightly but he was still at work in a police station. Hisvisual acuity and neurological status had not altered exceptthat the knee jerks could be elicited only on reinforcement.Nerve conduction studies showed only a slight deteriora-tion since the first study.

Case 4 (RGHC HX 1340)A retired storeman aged 60 years first noticed unsteadinessof gait at the age of 48 years which slowly progressed forc-ing him to walk with a stick. His vision had slowly deterio-rated over many years and retinitis pigmentosa had beendiagnosed when he was aged 30 years. He had previouslybeen a heavier drinker but in recent years drank 40-60 g ofalcohol per day and smoked 20 cigarettes per day. Therewas no family history of visual loss or progressive neuro-logical disease and his parents were unrelated. On examin-ation, his verbal IQ was 122 (WAIS). The sense of smellwas normal. He was able only to count fingers with botheyes. Cataracts and retinitis pigmentosa were present.There was no ptosis nor abnormality of extraocular move-ments, and the remaining cranial nerves were normal.There was no wasting, and power and tone were normal inupper and lower limbs. Finger-nose testing was accuratebut rapid alternating movements of hands were abnormaland there was marked impairment of co-ordination of thelower limbs. The deep tendon reflexes were present andplantar responses were flexor. He had a wide based, ataxicgait. Sensation was normal in upper limbs but appreciationof pin-prick was absent below the mid-calf level and vibra-tion sense was absent at the ankles. Light touch and joint

position were normal. General examination was normalapart from a patchy, generalised eczematous rash.Audiometry revealed bilateral high tone sensorineuralhearing loss.He was reviewed 10 years later. He was confined to a

wheelchair because of severe ataxia. Speech was very slur-red. He was completely blind; there were dense cataractswhich obscured any view of the fundi. His pupils were4 mm in diameter and unreactive to light and accommoda-tion. He was not deaf. Apart from slight wasting of the 1stdorsal interossei, there was no wasting or weakness. Tonewas normal but there was an intermittent coarse restingtremor in the fingers. Tests of co-ordination in the upperand lower limbs were grossly impaired. The deep tendonreflexes and plantar responses were unchanged. Vibrationsense was absent at the iliac crests.

HAEMATOLOGICAL AND BIOCHEMICALINVESTIGATIONSHaemogloblin, white cell count, erythrocyte sedimentationrate, serum electrolytes, serum creatinine, serum proteinsand electrophoretic pattern, liver function tests, serumcholesterol, fasting blood glucose, serum B12 and folatelevels, thyroid function studies, serological tests for syphilisand urinalysis were normal. In two patients (cases 1 and 3)there was an increase in serum triglycerides and lipid elec-trophoretograms showed an elevation in the pre-f3 lipo-protein concentration. The results of the cerebrospinalfluid (CSF) protein measurements are shown in table 1. Inall cases, the CSF cell count, and serological tests forsyphilis, and glucose levels were normal.Serum phytanic acid levels were measured in all patients,

and were not increased.

RADIOLOGICAL STUDIESChest and skull radiographs were normal. Results ofneuroradiological studies are summarised in table 1.

ELECTROPHYSIOLOGICAL STUDIES (Table 2)Sensory action potentials were abnormal in all patients.Motor conduction velocity was normal in patients 2 and 3but in patients 1 and 4, was reduced in the lateral poplitealnerve. The ulnar mixed nerve action potential was reducedin amplitude in patients 2 and 3. A lateral popliteal mixednerve action potential could not be recorded in any of thepatients.

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Mixed nerve action potentials

Ulnar nerve Lateral popliteal nerve

Latency Amplitude Latency Amplitude(MtS) (AV) (M) OAV)NR NR - 054 4 - 05-9 26 - 0NR NR - 0

4-1-67 28-88 5-1-8-1 3-15

Table 3 Total myelinated fibre densities in sural nervesofpatients and controls

Patient Fibre density (X103 mm-2)

1 1-662 0-783 5-904 3-03

Control range3' 3-81-6-42 (mean 4-57, SD: 0-89).

HISTOLOGICAL STUDIES

The total myelinated fibre densities2 of the four suralnerves and the range in control patients are shown in table3. In cases 1, 2 and 4 the densities were below the controlrange.

c c. xski4-. f, o ell

It may be seen from figs 1 and 2 that the density ofmyelinated fibres of all diameters was reduced in cases 1and 2 but that larger diameter fibres were predominantlyaffected. By contrast, in case 4, there is a marked reductionin the numbers of small myelinated fibres. Electron mi-croscopy2 revealed no specific abnormalities in any of thenerves. There was no evidence of demyelination, andonion bulbs were not seen.

Discussion

All four patients had retinitis pigmentosa withimpaired visual acuity, night-blindness and con-sticted visual fields, a predominantly sensoryperipheral neuropathy and cerebellar ataxia. Threeof the patients had sensorineural deafness and threehad radiological evidence of cerebellar atrophy. Inother respects their clinical features differed. Inpatients 1 and 2 the onset of symptoms was beforethe age of 20 while in patients 3 and 4, the age ofonset of symptoms was after 40, although retinitispigmentosa has been observed in patient 4 when hewas aged 30. Patient 1 was of low intelligence andhad extensor plantar responses while the other threewere of normal intelligence and had flexor plantarresponses. Deep tendon reflexes were diminished orabsent in patients 1, 2 and 3 but were present inpatient 4. None of the patients gave a family history

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Fig 1 Photomicrographs ofsections ofsural nerves from a control subject and from cases 1-4.Flemmings-Kulchitsky haematoxylin.

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of parental consanguinity, progressive visual failureor progressive neurological disease. Therefore, ifany of these patients has an inherited condition it islikely that the transmission is by an autosomal reces-sibe or X-linked recessive gene.

Abnormalities of nerve conduction, predomin-antly in sensory fibres, were found in all patients. Onsural nerve biopsy there was a reduction in densityof myelinated fibres in all patients, except case 3. Noevidence of segmental demyelination was found onteased fibre studies or on electron microscopy, andno onion-bulb formations were visible.

In all cases, the diagnosis of Refsum's disease wassuspected initially on clinical grounds, but finallyexcluded by the failure to demonstrate elevatedserum phytanic acid levels that are essential for thediagnosis.3 The most constant clinical features ofRefsum's disease, which has an autosomal recessivemode of inheritance, are retinitis pigmentosa, cere-bellar ataxia, peripheral neuropathy and elevatedCSF protein concentration without pleocytosis.3 Thefirst three of these features were present in all ourpatients, but the CSF protein concentration wasincreased in only one case. Other clinical featureswhich may be present in Refsum's disease are sen-

sorineural deafness (present in three of ourpatients), abnormal pupillary reactions and cataracts(present in two of our patients), anosmia, car-diomyopathy, skeletal malformations and skinchanges including icthyosis.3 The symptoms usuallyappear in the first three decades of life; in two of ourpatients the onset was in the fifth decade.The peripheral neuropathy in Refsum's disease

may have a relapsing and remitting course. Distalmuscle wasting may be a prominent feature and thenerves may be palpably enlarged. Electrophysio-logical studies usually demonstrate marked slowingof motor conduction.3 The pathological features arethose of a hypertrophic neuropathy, with segmentaldemyelination and reduplicated Schwann cell pro-cesses producing the characteristic appearance ofonion-bulb formation.4 None of these clinical, elec-trophysiological and pathological features of achronic demyelinating neuropathy were present inour cases.

Retinitis pigmentosa, deafness, ataxia, peripheralneuropathy and elevated CSF protein concentra-tions may be found in patients with the Kearns-Sayre syndrome which usually presents before theage of 20 years.5 None of the patients in the present

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study had either ptosis or ophthalmoplegia and onlyone had a raised CSF protein concentration. Noneof our patients had ECG evidence of heart blockwhich is a frequent finding in the Kearns-Sayre syn-

drome.5 In patients with the Kearns-Sayre syndromemuscle biopsy shows ragged-red fibres on the tri-chrome stain and abnormal mitochondria on elec-tron microscopy.6 None of our patients had a musclebiopsy performed but on clinical grounds, this diag-nosis may be excluded.Massion-Vemiory, Dumont and Potvin7

described a 43-year-old man who developedretinitis pigmentosa, ataxia, amyotrophy and milddistal sensory loss at the age of 34. His CSF proteinwas elevated. A nerve biopsy showed neither hyper-trophic changes nor signs of active degeneration.One of this man's sisters had retinitis pigmentosawhile another had atypical retinal pigmentarychanges. However, neither his parents nor his foursiblings had any neurological disease so the retinalchanges might have been unrelated as could be thecase in some or all of our patients. Dyck8 hasclassified this patient and a number of similar sib-ships (in whom serum phytanic acid was normal) as

hereditary sensory and motor neuropathy type VII.However, the considerable degree of ataxia withminimal sensory loss in the patient reported byMassion-Vemiory et al7 suggests that there mighthave been involvement of the cerebellum or

spinocerebellar pathways or both as well as theperipheral nerves.

Two similarly affected individuals have beendescribed in a family of four generations.9 Six othermembers of the family had distal muscle wasting andof these, one had optic atrophy and four had matur-ity onset diabetes mellitus. The amyotrophy andretinitis pigmentosa are apparently both dominantlyinherited in this family but the former may be pres-ent in some individuals who have normal retinae.Refsum's disease and abetalipoproteinaemia were

excluded in the propositus who also had congenitalsyphilis. The CSF protein was normal and motorconduction velocities were mildly reduced. Postmortem examination of one of the members of thisfamily who developed neurological disease after theinitial report in 1968 revealed severe demyelinationof the peripheral nerves, spinal roots, dorsal col-umns, spinocerebellar tracts and optic chiasm.'0Although the clinical features of some of the mem-bers of this family resemble those of our fourpatients and the case of Massion-Vemiory et a17 theyprobably in fact have a different disorder becausedemyelination was not found in the peripheral nervebiopsies of these patients.

Patients have been described as having Refsum'sdisease in whom the serum phytanic acid concentra-

tions have been found to be normal. One patient"' 12was subsequently shown to have the typical clinicaland histopathological features of the Kearns-Sayresyndrome.5 Although muscle pathology is lacking inthe case of Solcher'3 it is likely that his patient alsohad the Keams-Sayre syndrome as there was bilat-eral ptosis and impairment of extraocular move-ments which are not features of Refsum's disease.Another patient with the clinical features ofRefsum's syndrome with normal phytanic acidlevels'4 had a liver biopsy in which there were anumber of abnormalities including abnormal vesicu-lated mitochondria. However, the appearance wasnot that of the abnormal liver cell mitochondria inthe Kearns-Sayre syndrome in which are seen fusedarrays of cristae.'2 This patient subsequently diedand was presented as a case of diffuse cerebralsclerosis's with patchy demyelinated sudanophiliclesions and punctate perivascular calcification in thebrain. Phytanic acid metabolism in cultured skinfibroplasts was normal. Ron and Pearce'6 describeda 27-year-old male patient whose symptoms beganat the age of 8 years and who had signs and symp-toms which were consistent with Refsum' s syndromeexcept for extensor plantar responses and normalCSF protein. Motor conduction velocities were onlymildly slowed. No phytanic acid was detected in theserum and there was no response to a phytate-freediet.

Retinitis pigmentosa, sensorineural deafness,cerebellar ataxia and peripheral neuropathy occurtogether in Cockayne's syndrome.'7 However thiscondition should be readily recognisable because ofcertain clinical features which include onset ofinfancy, microcephaly, dwarfism, kyphosis, flexiondeformities, loss of subcutaneous fat, a distinctivephysiognomy, anhidrosis, marked cutaneous photo-sensitivity to ultraviolet light and deterioration inintellect. Death often occurs in childhood.'8 Themajor abnormality in the brains of patients withCockayne's syndrome are patchy demyelination andperivascular calcification.'8 Marked slowing ofmotor conduction velocity was recorded in onepatient with Cockayne' s syndrome whose nervebiopsy showed segmental demyelination.19 Apartfrom the presence of retinitis pigmentosa, deafness,ataxia and neuropathy, none of our cases have otherfeatures to suggest Cockayne' s syndrome exceptcase 1 who is mentally retarded and of short stature.He does not have skin photosensitivity nor ademyelinating neuropathy. Unlike most cases, hewas still able to perform menial tasks at the age of28. However a patient has been described recentlywho probably has Cockayne's syndrome but wasatypical in that her intellectual and motor functionswere moderately well preserved when seen at the

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age of 25 years.20The neurological signs in abetalipoproteinaemia

include retinitis pigmentosa, ataxia, peripheralneuropathy, but not usually deafness. These signsare manifest by the age of 20 years and are precededby a history of diarrhoea and steatorrhoea of someyears duration. Usually, patients with abetalipopro-teinaemia have marked muscle wasting and weak-ness, kyphoscoliosis and are confined to awheelchair by the age of 20.21 The non-neurologicalhallmarks of the condition are the presence of acan-thocytes in the blood film, the absence of betalipo-proteins and low concentrations of cholesterol in theserum. None of our patients had any of theseabnormalities.

Retinitis pigmentosa, deafness, ataxia and mentalretardation may occur together in patients withHallgren's syndrome22 or with juvenile or adultonset types of lipidosis.23 However, there is no clini-cal evidence of peripheral neuropathy in patientswith these disorders. In Hallgren's syndrome, deaf-ness is congenital and usually profound, whilepatients with a lipidosis frequently have epilepsy,myoclonus or both which was not the case in any ofour patients.

Retinitis pigmentosa is very rare in Friedreich'sataxia, but may occur in association with olivo-ponto-cerebellar atrophy, and some other heredit-ary ataxias.24-27 None of our patients had the clinicalfeatures of Friedreich's ataxia or the characteristicreduction in density of large diameter fibres in thesural nerve.28 However it is possible that they rep-resent sporadic cases of olivo-ponto-cerebellaratrophy, or a spinocerebellar degeneration. Patient1 had evidence of pyramidal tract involvementwhich is consistent with olivo-ponto-cerebellaratrophy29 or spinocerebellar degenerations.30 Inthree cases there was radiological evidence of cere-bellar atrophy, and the electrophysiological andpathological features of the peripheral neuropathywere consistent with those reported in these condi-tions.2 The precise relationship of the disorderaffecting these patients to other degenerative dis-eases involving cerebellum, spinal cord andperipheral nerves, remains uncertain.

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4 Fardeau M. Pathology of Refsum's disease. In: Dyck PJ,Thomas PK, Lambert EH, eds. PeripheralNeuropathy. Philadelphia: Saunders, 1975:881-90.

5 Berenberg RA, Pellock JM, Di Mauro S, et al. Lumpingor splitting? "Ophthalmoplegia-plus" or Keams-Sayre syndrome? Ann Neurol 1977;1:37-54.

6 Karpati G, Carpenter S, Larbrisseau A, Lafontaine R.The Kearns-Shy syndrome. J Neurol Sci 1975;19:133-51.

Massion-Verniory L, Dumont E, Potvin AM. Retinitepigmentaire familiale compliquee d'une amyotrophieneurale. Rev Neurol (Paris) 1946;78:561-71.

8 Dyck PJ. Atrophy affecting peripheral motor, sensoryand autonomic neurons. In: Dyck PJ, Thomas PK,Lambert EH, eds. Peripheral Neuropathy. Philadel-phia: Saunders, 1975:864.

9 Furukawa T, Takagi A, Nakao K, Sugita H, TsukagoshiH, Tsubaki T. Hereditary muscular atrophy withataxia, retinitis pigmentosa, and diabetes mellitus. Aclinical report of a family. Neurology (Minneap)1968;18:942-7.

10 Kondo K. Peripheral neuropathy associated with ataxia,retinitis pigmentosa and diabetes mellitus. In: VinkenPJ, Gruyn GW, eds. Handbook of Clinical NeurologyVol 42. Amsterdam: North Holland Publishing Com-pany, 1981:334-5.

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18 Guzzetta F. Cockayne-Neill-Dingwall syndrome. In:Vinken PJ, Bruyn GW, eds. Handbook of ClinicalNeurology Vol 13. Amsterdam: North Holland Pub-lishing Company, 1972:431-40.

4 Moosa A, Dubowitz V. Peripheral neuropathy in Cock-ayne's syndrome. Arch Dis Child 1970;45:674-7.

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23 Cummings JN. The lipidoses. In: Vinken PJ, Bruyn GW,eds. Handbook of Clinical Neurology Vol 10. Amster-dam: North Holland Publishing Company, 1970:325-61.

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