- ACTA OPHTHALMOLOGICA SCANDINAVICA 1996

Full-field electroretinograms in individuals with the Laurence- Moon-Bardet-Biedl syndrome Ruth Riise', Sten Andreasson2 and Kristina Tornqvist2

Department of Ophthalmology', Central Hospital of Hedmark, Hamar, Norway, Department of Ophthalmology', University Hospital of Lund, Lund, Sweden

ABSTRACT. Purpose: To evaluate rod and cone function in individuals with the Laurence- Moon-Bardet-Biedl syndrome. Methods: We obtained full-field electroretinograms in 36 patients. If responses less than 10 pV were recorded with single white flashes a special technique with narrow band filter and computer averaging was used. Results: No rod responses to dim blue light could be obtained in any of the pa- tients. Residual cone flicker responses were measurable in 28 of the individuals. Those with amplitudes < 0.05 pV were significantly older than those with ampli- tudes > 1.00 pV. The ERG pattern was consistent within affected pairs of siblings in 8 families. Conclusion: The retinal dystrophy in Laurence-Moon-Bardet-Biedl syndrome is primarily a rod-cone dystrophy, but even cone flicker amplitudes are severely re- duced with further progression with age. There is no intrafamilial variability of the electroretinograms in affected siblings.

Key words: full-field electroretinograms - tapetoretinal degeneration - Laurence-Moon-Bardet- Biedl syndrome.

Acta Ophthalmol. Scand. 1996: 74: 618-620

n 1866, Laurence and Moon described I four siblings with varying expressivity of the features retinitis pigmentosa, obesity, hypogenitalism and mental retar- dation (Laurence & Moon 1866). These cardinal features were later supple- mented by neurological symptoms (Hut- chinson 1900; Lavy et al. 1995), polydac- tyly (Bardet 1920; Biedl 1922), renal dis- ease (Churchill et al. 1981; Harnet et al. 1988) and dental anomalies (Kobrin et al. 1990; Lofter0d et al. 1990; Borgstrom et al. 1996).

The visual function in this group of pa- tients has been evaluated previously, but studies of large groups of patients have only been published by few authors (Am- mann 1968; Riise 1987; Green et al. 1989; Fulton et al. 1993).

Earlier studies on electroretinograms of patients with the LMBB syndrome have shown retinal dysfunction in young patients due to either rod-cone or cone- rod dysfunction (Campo & Aaberg 1982; Rizzo et al. 1986; Jacobson et al. 1990;

Harrison & v Heuven 1985; Lavy at al. 1995; Iannaccone et al. 1996). Other studies with measurements of dark adap- tation threshold levels have noted an early loss of rods (Riise 1987, Green et al. 1989; Leys et al. 1988; Jacobson et al. 1990). In advanced cases of the syn- drome, ERG studies have demonstrated low or non-detectable responses (Krill et al. 1960; Stanescu & Wawernia 1970; Iannaccone et al. 1996).

In this study we evaluated the rod and cone function in the LMBB syndrome by full-field electroretinography in 36 Scan- dinavian patients from 25 families. In ad- dition, we examined the electroretino- grams for intrafamilial variability in eight families with several affected members.

Material and Methods The 36 individuals included in this study were defined as LMBB syndrome cases if they had retinal dystrophy and at least

two more of the traditional cardinal signs of the syndrome (retinal dystrophy, obesity, polydactyly, hypogenitalism and mental retardation). The material con- sists of 18 men and 18 women with an average age of 26 years spanning from 3 to 57 years. The participants were re- cruited from three Scandinavian coun- tries (Norway 15, Sweden 11 and Den- mark 10).

Eight families with at least two affected members were studied with respect to in- trafamilial variability.

The patients investigated were in- cluded in a study of the ocular findings in 44 individuals with the LMBB syndrome (Riise et al. 1996), where the methods of the ophthalmological examination have been described.

Electroretinograms were recorded in a Nicolet Compact Four analysis system as described previously (AndrCasson et al. 1993). After 40 min of dark adaptation and dilatation of the pupil with topical phenylephrine and cyclopentolate, a Bu- rian-Allen bipolar contact lens ERG electrode was applied together with a ground electrode on the forehead. Re- sponses were obtained with a wide band filter (- 3 dB at 1 Hz and 500 Hz), stimu- lating with single full-field flashes (100 ps) with blue light (Wratten filter #47, 47A and 478 combined; 25 cd/m'), and with white light (7500 cd/m2). Light adapted, cone responses were obtained with 30Wz flickering white light (7500 cd/m2) averaged from 20 sweeps.

If responses less than 10 yV were re- corded with single white flashes as de- scribed above, recordings were also ob- tained with computer averaging (30 flashes), a bipolar artefact rejecter and a line frequency notch filter (50 Hz). In ad- dition, responses to 200 flashes of flicker- ing white light (30 Hz) were obtained with an external analogue narrow band filter

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ACTA OPHTHALMOLOGICA SCANDINAVICA 1996 -

(Kron-Hite Narrow Band Tracking Filter, model 3800) added to the Nicolet Com- pact Four machine. The narrow band fil- ter was tuned to 30 Hz (- 12 dB at 29 Hz and 31 Hz).

Results Visual acuity and visual fields Only 9 persons had a visual acuity better than 0.1, and the average age in these pa- tients was 9 years. All who could be tested with the standardized object, V 4 e and 1:4e, showed restriction of their visual fields. The fields were greater than 35 de- grees in only 2 persons, and then with the largest object. Mostly, the fields were con- stricted to 10-15 degrees with V4e.

Dark adaptation threshold The dark adaptation threshold was elev- ated in all who could be tested and was elevated less than 4 log units in only two of the persons.

Electroretinogram No rod responses to dim blue light could be obtained in any of the patients. Full- field electroretinograms from the 36 pa- tients demonstrated residual cone flicker responses from at least one eye in 28 of the individuals, however, even in the youngest patient, 3 years old, significant reductions of the amplitudes were found. The mean age at time of examination was significantly lower in the individuals with cone flicker amplitudes > 1.0 pV than those with amplitudes <0.05 pV ( p = 0.001, unpaired t-test) (Table 1). Exam- ples of electroretinograms recorded from two persons with LMBB syndrome are shown in Fig. 1. Remaining cone b-wave and cone flicker responses were meas- ured in the younger patient, while the small cone flicker responses in the older

Table 1. The mean cone flicker amplitudc (range in brackets) in the best eye and the mean age (range in brackets) at time of exam- ination in 36 Scandinavian patients with the LMBB syndrome.

Amplitude of cone re- No. of Age sponse to flickering patients (years) white light (yV)

Mean (range) Mean (range)

0.005 (0.00- 0.04) 8 35 (21-57) 0.25 (0.05- 0.50) 16 27 ( 7-45) 0.79 (0.54- 1.00) 5 29 (14-37)

15.59 (1.10-38.00) 7 13 ( 3-29)

7 years

23 years

Fig. 1 . Full-field electroretinograms from two patients with the LMBB syndrome. No rod respon- ses were detected with dim blue light at any age. Remaining cone b-wave and cone flicker respon- ses could be measured in the youngest patient when stimulating with white light or 30-Hz flicker- ing white light. To detect the small cone flicker amplitudes in the older patient a bandpass filter was necessary.

i I White I

I

I

30 Hr i Bandpassed [ I averagefrom I 1 20osweeps I

I I I I I I I I I I I I I I I I I I

I - -.-+-I

I I

I I I Full-field electroretino- I I I I I I

f I I I

I I

Fig. 2. 38 years h - ~ ~ ~ - ~ , - ~ ~ - ~ ~ = . - ~ ~ ~ - - -

grams from 3 patients in the I I I

same family. The cone I I I flicker amplitude was less I

than 0.8 yV thus severely reduced or non-detectable 39 years

I I I I

15 i: ms

I I I I I 2

J2 10 ins

responses even with a band- I I I

pass filter. The small dif- ferences in the amplitudes I of the 3 siblings are not sig- nificant.

patient only could be measured by use of a bandpass filter.

The ERG pattern did not demonstrate any significant intrafamilial variability in any of the eight families with more than one member with the disease (Fig. 2).

Discussion We have used the broadly based pheno- type concept of the LMBB syndrome (Rizzo et al. 1986; Kobrin et al. 1990) for our description of the participants in this study, although the syndrome has been dividcd into at least three clinical entities: the Laurence-Moon, the Bardet-Biedl and the Alstriim syndromes (Schachat & Maumenee 1952). These subgroups all

comprise retinal dystrophy, obesity and hypogenitalism but should be separated by presence or absence of paraplegia, polydactyly, mental retardation, diabetes mellitus and deafness. However, the sub- groups cannot always be separated be- cause of considerable inter- and intra- familial variability of these features (Green et al. 1989; Riise et al. 1995).

Early loss of rod and cone function measured by dark adaptation threshold and electroretinogram in LMBB patients has been shown earlier (Riise 1987; Green et al. 1989; Leys et al. 1988; Jacob- son et al. 1990; Fulton et al. 1993). It has been discussed whether the retinal dis- ease was due to a cone-rod or a rod-cone dystrophy (Fulton et al. 1993; Lavy et al. 1995; Iannaccone et al. 1996). The pres-

619 -

ent study confirms that the retina1 dys- trophy in LMBB patients is primarily a rod-cone degeneration even if the order of onset of visual problems varies (Riise et al. 1996). No rod responses were measured in any of the patients and dark adaptation thresholds were elevated in all, even the youngest.

Previous studies have demonstrated very low and mostly non-detectable ERG responses in the LMBB syndrome (Krill et al. 1960; Riise 1987; Fulton et al. 1993; Lavy et al. 1995; Iannaccone et al. 1996). We used a special technique with a nar- row band filter and computer averaging to measure cone flicker responses (An- dreasson et al. 1988). Our study on 36 pa- tients indicated very low remaining reti- nal function, but still with measurable cone flicker amplitude in 28 of the pa- tients. This can be used for following ob- jectively the rate of progression of the re- tinal disease, as previously applied in other forms of retinitis pigmentosa (Ber- son et al. 1985).

Although intrafamilial variation of the onset of visual symptoms as well as of the rate of decline of visual acuity has been noted (Riise et al. 1995), we could not demonstrate any variability in the elec- troretinograms when age was taken into consideration. On the contrary, we found the same trend in the affected persons both within and between the families with no rod responses and severe reduction of cone flicker amplitudes even in the youn- gest patients.

This study of rod and cone function in LMBB patients has demonstrated:

1. Early involvement of primarily rods from which no ERG responses could be recorded in any of the patients.

2. Severely reduced cone flicker am- plitudes with further progression with age.

3. No intrafamilial variability of the electroretinograms in 8 pairs of siblings.

Acknowledgments This study was supported by grants from Mar- git Thyselius Fond, Sigvard & Marianne Ber- nadottes Forskningsstiftelse, The Swedish So- ciety of Medicine, The Faculty of Medicine, University of Lund and The University Hospi- tal of Lund, Sweden, The Swedish Medical Research Council (project 14X 2321), Hed- mark County Council, Norway, The Nor- wegian Association of the Blind, The Danish Association of the Blind and The Danish So- ciety for Prevention of Blindness. The study was carried out within a research organization sponsored by The International RP Founda- tion.

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Received on January 29th. 1996.

Corresponding author: Ruth Riise Department of Ophthalmology Central Hospital of Hedmark N-2300 Hamar, Norway. Tel47-625-16242. Fax 47-625-23892.