ACTA OPHTHALMOLOGICA 65 (1987) SUPPI. 182, 128-131

Visual Function in Laurence-Moon-Bardet-Biedl Syndrome A Survey of 26 Cases

by Ruth Riise

Department of Ophthalmology (Head: D. Riise), Hamar Sjukehus, Norway

Abstract In 1984,32 persons with Laurence-Moon-Bardet- Biedl syndrome (LMBB syndrome) were registered in Norway. Of these, 26 stayed for 10 days at the Frambu Health Centre, where they consulted a pediatrician, a psychologist, a dentist, a social worker, a geneticist, a teacher for the blind and an ophthalmologist.

The ocular examination showed the eye disease in cases of LMBB syndrome to be homogeneous and fulminant tape- toretinal degeneration of the retinitis pigmentosa type.

Key words: Laurence-Moon-Bardet Biedl syndrome. Pigmen- tary retinopathy. Tapetoretinal degeneration. Retinitis pig- mentosa. Blindness. Obesity. Polydactyly. Hypogenitalism. Mental redardation.

Laurence-Moon-Bardet-Biedl syndrome (LMBB syndrome) is a congenital, autosomal recessive hereditary disease. It was first described by the British ophthalmologists Laurence and Moon (1866). In a family of 10 brothers and sisters, 4 had varying degrees of retinitis pigmentosa, obesity, mental retardation and hypogenitalism. Bardet (1920) described a patient with corresponding findings and polydactyly, as did Biedl(l922).

On the basis of their own observations of 48 cases of LMBB syndrome Klein and Amman (1969) reported the following frequencies for the chief symptoms: Tapetoretinal degeneration loo%, obesity loo%, skeletal anomalies (polydydactyly, syndactyly, brachydactyly) 85 %, mental retardation 70% and hypogenitalism 45%. This agrees with an earlier survey by Bell (1958). Klein and Amman (1969) also found increased occurrence of renal disease with arterial hypertension, which has been confirmed among others by Churchill et al. (1981), Alto and

McDonald (1973) and Camp0 and Aaberg (1982). Neurological findings with abnormal EEG and deaf- ness were also reported, and Burn (1950) too described the latter. Klein and Amman described visual function as having been affected from school age and progressing to practical blindness at the age of 30. In most cases, they described fundus findings as atypical retinitis pigmentosa, with the pigmen- tation first appearing at a late stage of development, but they also mentioned retinitis punctata albescens and congenital amaurosis of Leber. They were furthermore able to demonstrate a preponderance of refractive errors, especially myopia.

Other authors have described nystagmus (Laur- ence and Moon (1866) Burn (1950); macular pig- mentation (Clay 1933); strabismus and cataract (Eh- renfeld 1970); and iriscoloboma and anophthalmia (Francois 1953). Marshall (1985) showed by means of microscopic studies that some of the receptor cells in both the peripheral and the central retina die, and that the remaining receptor cells lose their outer segments while the inner segments swell. In the pigment epithelium, inclusion bodies were found containing lipofuchsin, melanolysosomes and melano- fuchsin.

Materials and methods

In 1984, 32 persons with LMBB syndrome were registered in Norway, in 24 families. They were contacted through a physician and interviewed at home by a teacher for the blind. They were then offered a stay at Frambu Health Centre, where medical, socio-medical and pedagogical information is made available to patients with rare deseases. 26

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of the 32 went for a 10-day stay, during which they were contacted by a pediatrician, a psychologist, a dentist, a social worker, a geneticist, a teacher for the blind and an ophthalmologist. There were 14 women and 12 men aged from 4 to 61. Table 1 shows the age distribution. Following medical examinations, which confirmed the diagnosis, ophthalmological examinations were carried out by the author. There were no special premises for such examinations, and all equipment had to be brought from outside.

Table 1

Age in years Number of patients

0 - 20 11 21 -40 12 41 - 61 3

Age distribution in 26 patients with Laurence-Moon-Bardet- Biedl Syndrome.

Visual acuity was measured using the Sheridan Gardiner test at a distance of 3 metres. Dark adap- tation was assessed with Goldman Weeker apparatus in combination with practical tests. Colour vision was examined by means of the Ishihara test and the City University test.

Eye position was assessed using light reflex and the cover test, and eye movements were judged by inspection.

Examinations with a hand-held slit lamp were carried out before and after cycloplegia.

Refraction was measured subjectively and by retinoscopy in cycloplegia. Visual fields were tested with Goldman perimetry supplemented with Don- ders’ test.

Direct ophthalmoscopy was carried out, and in some cases patients were referred to an eye clinic for electroretinography.

Intraocular pressure was measured by Schicatz’ tonometry.

Results

Examinations by a pediatrician and an ophthalmo- logist showed the following distribution of the cardinal symptoms: tapetoretinal degeneration loo%, obesity 96%, poly/ syndactyly 77%. In addition, short, broad hands and feet and some incidence of

flat feet were found in 81% and elevated blood pressure in 50%. The dentist found short dental roots in 85%.

Information was incomplete concerning mental retardation and hypogenitalism, but gave the im- pression that mental retardation was not pronounced and occurred rarely, whereas hypogenitalism was frequent.

Table 2

Visual Acuity Number of patients

316 31 9-3/36 3/60-light perception

1 9

16

Visual acuity in 26 patients with Laurence-Moon-Bardet- Biedl Syndrome, measured with Sheridan Gardiner test at a distance of 3 metres.

As shown in Table 2, visual acuity was reduced in all cases and in the majority to 3/60 or worse. The reduction was moderate up to the age of 13, after which it progressed rapidly to reach 3/60 or worse before the age of 30. Light perception had been retained in all cases.

Dark adaptation had been reduced or lost in all cases. Adaptometry could only be carried out on 5 persons. The vision of the majority of the others was too poor, so that dark adaptation had to be assessed by means of practical tests supplemented with the‘person’s own information. In Figure 1, the

Fig. 1

Dark adaptation measured in Goldman-Weekers adaptometer on an 1 I-year-old patient with Laurence-Moon-Bardet-Biedl Syndrome, compared with a normal curve (N).

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adaptometry curve of an 11 year-old with LMBB syndrome is compared with a normal curve.

Colour vision could also only be tested in 5 persons. One 4 year-old had to be excluded because of her age, and the vision of the others was too poor. None were able to identify any of the test symbols on Ishihara tables. The City University test showed tritan defects in 3 persons and more or less normal states in 2.

Eye position showed a preponderance of divergent strabismus (Table 3), in addition to frequently occurring conjugate upward deviation. Strabismus was related to poor vision and was taken to be secondary. Those with poorest vision also showed preponderance of nystagmus and restricted mobility.

7 of the 26 persons had cataract. The youngest was aged 30. The cataracts were stellate and located in the posterior subcapsular part. There was nothing to report concerning pupils.

Table 3

Ocular position Number of patients

Parallel Esotropia Exotropia

10 1

15

Ocular position in 26 patients with Laurence-Moon-Bardet- Biedl Syndrome.

Visual fields could be measured by Goldman perimetry in 8 cases. There were peripheral defects from the age of 7, progressing to tube vision with

Fig. 2

Visual field measured in Goldman perimeter on a patient aged 1 1 with Laurence-Moon-Bardet-Biedl Syndrome.

some peripheral remains at the age of 18. Figure 2 shows perimetry in an 1 1-year-old girl with LMBB syndrome.

Retinoscopy showed preponderance of myopia with astigmatism. Table 4 shows refraction expressed in terms of spherical equivalent.

Table 4

Refraction Number of patients

Myopia( + 1.5 Hypermetropia2 + 1.75 Emmetropia Measurement not possible

15 3 3 5

Refraction (spherical equivalent) measured by retinoscopy in cycloplegia on 26 patients with Laurence-Moon-Bardet- Biedl Syndrome. In 5 cases measurement was not possible because of cataract.

Ophthalmoscopic examination showed pale optic disc and constricted vessels in all cases. The youngest showed more than normal central reflexes. The typical bone spicules were only found in late stages with visual acuity close to 3/36. In the present material, bone spicules were found in 20 persons. 8 showed pigment mottling in the macula area.

Electroretinography was carried out on 2 persons in whom the ophthalmoscopic findings were un- characteristic; the curve was extinguished in both cases. Intraocular pressure was measured in 7 adults and found normal.

Discussion

The investigation shows that the eye disease in cases of LMBB syndrome is a fulminant tapetoretinal degeneration of the retinitis pigmentosa type.

Characteristic ophthalmoscopic findings are pale optic disc and constricted vessels. The typical bone spicules only occur at advanced stages of the disease.

Dark adaptation is reduced from earliest child- hood. Visual field defect can be demonstrated from the age of 7, and visual aquity is noticeably reduced from the age of 13 to reach 3/60 at the age of 30. Light perception is retained.

General findings are obesity, hypogenitalism, various skeletal and dental anomalies and elevated blood pressure with indications of renal disease. Signs of mental retardation, on the other hand,

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are not conspicuous. The result of these exami- nations will be published elsewhere.

References

Alton D C & McDonald P (1973): Urographic Findings in the Bardet-Biedl Syndrome. Radiology 109: 659-663.

Bell J (1958): The Laurence-Moon Syndrome. In: Penrose L S (ed.), The Treasury of Human Inheritance. Cambridge, England. Cambridge University Press, 5: 51-96.

Biedl A (1922): Ein Geschwisterpaar mit adiposo-genitaler Dystrophie. Dtsch Med Wochenschr 4: 1630.

Bum R A (1950): Deafness and the Laurence-Moon-Biedl Syndrome. Brit J Ophthalmol34 65-88.

Campo R V & Aaberg T M (1982): Ocular and systemic Manifestations of the Bardet-Biedl Syndrome. Am J Ophthalmol94 750-761.

Churchill D N, McManamon P & Hurley R M (1981): Renal Disease-a sixth Feature of the Laurence-Moon-Biedl Syn- drome. Clinical Nephrology 3: 151-154.

Tr. Am Ophthalmol SOC 31: 274-288.

Bardet-Biedl Syndrome in Israel. Am J Ophtbalmol70: 524-532.

Clay G E (1933): Laurence-Moon-Biedl Syndrome.

Ehrenfeld E N, Rowe & Auerbach E (1970): Laurence-Moon-

Francois J (1953): A propos d’une famille prisentant des anomalies du type colobomateux depuis le colobome uni- laterale associte au syndrome de Bardet-Biedl. Bull SOC belge Ophthalmol 104: 342-355.

Klein D & Amman F (1969): The Syndrome of Laurence- Moon-Bardet-Biedl and Allied Diseases in Switzerland. Clinical, Genetic and Epidemiological Studies. J Neurol Sci 9: 479-5 13.

Laurence J Z & Moon R C (1866): Four Cases of ((Retinitis Pigmentosa) occunng in the same Family, and accompanied by general Imperfections of Development. Ophthalmol Rev 2 3241.

Marshall J (1985): Personal communication.

Author’s address: Ruth Riise, Arvesens vei 33, N-2300 Hamar, Norway

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