Pseudoinflammatory fundus dystrophy: a follow-up study

Clinical Genetics 1990: 38: 21-32

Pseudoinflammatory fundus dystrophy: a follow-up study

ALDUR W. ERIKSSON’, ERKKI A. SUVANTO’, R. R. FRANTS’ AND HENRIK R. Fo~srus’ ‘Institute of Human Genetics, Medical Faculty, Free University, Amsterdam, The Netherlands,

*Eye Department, Satakunta Central Hospital, Pori, Finland, and 3Folkhalsan Institute of Genetics, Population Genetics Unit, Helsinki, Finland

We have performed a reinvestigation of a family with a presumably autosomal recessive form of pseudoinflammatory dystrophy, which we have followed for 25 years. The symptoms in this family are subretinal haemorrhages appearing at age 13-40 years in the central fundus, resulting in glial cicatrication in the outer retinal layers, progressive myopia and profound choroidal atrophy in the advanced stages of the disease. During the follow-up study, a new affected subject was found in the younger generation, and two collateral cases, who had earlier been considered as probably affected subjects, were now considered to have other fundus affections. The new case is the daughter of an affected female. The possibilities of an autosomal dominant mode of inheritance or pseudodominance are discussed. Extended genealogical studies showed that the parents of all the affected subjects, with the exception of the new case, have their origin in an area which was isolated until recently and have several common ancestors within the last 8-10 generations. Recessive inheritance also logically explains the appearance of the disease in so few other members in the vertical line of the family. To this fundus dystrophy, the rule of Lenz seems to apply: If more or less the same phenotype can be caused by both a recessive and a dominant gene, the phenotype caused by the recessive gene is generally manifest- ed earlier and by more severe symptoms.

Received 20 April, revised 17 October, acceptedfor publication 16 December 1989

Key words: autosomal recessive; bilateral hemorrhagic degeneration; choroid; consanguinity; longitudinal study; progressive myopia; pseudoinflammatory fundus dystrophy; retina

While studying X-chromosomal recessive retinoschisis in the province of Satakunta in southwestern Finland (Vainio-Mattila et al. 1969, Forsius & Eriksson 1980), we ran across an almost blind father being treated for choroiditis disseminata. The mother and three of the eight children of their family were also affected but, as we thought in the 1960s, by a different eye disorder, i.e. autosomal dominant pseudoinflammatory fundus dystrophy as described by Sorsby et al. (1949). However, after a longitudinal study lasting more than 20 years, we are

now convinced that all 10 members of this nuclear family have a fundus dystrophy of the recessive type.

The aim of this study is to demonstrate the importance of follow-up studies of rare ophthalmogenetic disorders with varying age of onset and varying progression.

Follow-up Studies 1966-1 980

In 1982 we published this family with pseudoinflammatory dystrophy with autosomal recessive inheritance, which we had fol-

22 E R I K S S O N ET A L .

Table 1

comparison of the two types of pseudoinflarnrnatory fundus dystrophy

Type Sorsby Type Lavia (Finland)

Age of manifestation Refraction error

in the 4th and 5th decade normal distribution

Visual acuity slowly lost Dark adaptation normal Peripheral retinal degeneration slight Colour vision seldom abnormalities Mode of inheritance autosomal dominant, McKusick

13690

~~ ~~ ~~

about 1WO years progressive myopia (up to -15

rel. rapidly lost disturbed 1-4 log units strong often secondary dyschromatopsia autosomal recessive, McKusick 26442

D)

lowed for 16 years (Forsius et al. 1982). The symptoms of the fundus dystrophy in this family are subretinal haemorrhages in the central fundus, increasing myopia in the ac- tive phase of the disease, glial cicatrication of the outer retinal layers, and profound choroidal atrophy, particularly in the advanced stages of the disease. Large numbers of deep hyaloid bodies in the retina can be seen to develop and again disappear in the same subjects. Fluorescein angiography demonstrated leakage through the pigment layer in the retinal tissue. The clinical pat- tern is similar to the autosomal dominant type of pseudoinflammatory dystrophy described by Sorsby et al. (1949) and later by others (for further references, see Hoskin et al. 1981 and Forsius et al. 1982). except that the disorder appeared earlier in this Finnish family, the members showed progressive myopia and the inheritance seemed to have an autosomal recessive mode (Table 1).

A detailed ophthalmological description of the findings of the affected members of this family up to 1980 can be found in our earlier report. Only three of the eight children were affected when we first investigated them in the mid 1960s. Our first tenta- tive diagnosis was therefore pseudoinflammatory dystrophy of Sorsby with an autoso- ma1 dominant inheritance (Fig. 1). Follow- up studies of probable infections (lues, tox- oplasmosis, histoplasmosis) causing central

choroiditis were negative. We followed the sibs with photographs of the fundus and clinical investigations, and we found that all five sibs earlier declared healthy now had the same or very similar symptoms (see Cases IX, 48-55 in Fig. 2.).

The parents both had large areas of degeneration in their retinas. The father had large pigmented scars all over the fundus resembling choroiditis disseminata, for which he had been treated earlier. During our longitudinal studies we could follow the changes of the fundus of the much younger wife from a stage with the typical glial scar in the macular area to more widespread degeneration throughout the fundus, thus coming closer to the clinical picture in her husband.

OUR DIAGNOSES IN 1966

Chroidlt is Pswdoinflmmtory 1 3 di rsminau ITbc?l 27 kndua dystrophy

V I I I

Fig. 1. Our diagnoses in 1966 of the family of the parents (V111,13 and V111,27 in Fig. 10) and their children. Only three of the eight children were affected. The eyes of the father had been treated for dis- seminated choroiditis (tbc?). The much younger wife had reached this stage of fundus dystrophy 14 years later than her husband in 1966. At that time, all of 'he eight children were affected as well (cf. Fig. 2).

P S E U D 0 I N F L A M M A T 0 R Y FU N D U S D Y S T R 0 P H Y 23

Follow-up Studies 1982-1989

We have reinvestigated this family, focusing on those members who were of the age to acquire the disease and on those who had signs which could possibly develop into the specific dystrophy.

Genealogical Studies Extended genealogical studies up to the 17th century showed that the parents and the grandparents of the eight children were related in many different ways (Fig. 2). We concluded that if both parents were affected with the same autosomal recessive gene, all their children must get the disease, which they did eventually. The ancestors of the parents had not been known to have bad eye-sight. We could investigate nine of the sibs of the parents; the other had died by the time we performed our first studies in this family. Only one of the sibs (VIII, 23) of the affected parents was affected.

Visual Acuity Fig. 3 shows the strong interindividual vari- ation in the progressive decrease of the visus, but there are also considerable intrain- dividual differences. E.g. in child nr. 7 (in the pedigree, IX,54) the right eye was blind already at the age of 24 but the left eye still has normal visual acuity at the age of 35. Child nr. 8 (1x55) still has good visus in both his eyes at the age of 33. But child nr. 5 (IX,52) already had strongly decreased visual acuity in both his eyes a t the age of 15. The mother (VIII,27) was completely blind in both her eyes around the age of 60, but at about the same age. the father (VIII,13) still had visual acuity of 0.5 and 0.4 in his right and left eye, respectively.

Refraction The myopia shows a tendency to increase progressively with age, particularly in the case of child 6 (IX,53) and the mother (VIII,27). On an average the decrease of

26442 Pseudoinflammatory fundus dystrophy

I1 1 .O -0 Investigated male, female 0610 Bad sight at the age of 10 t 60 I Consanguinity

0 - 9 ~ myopia

I

111

IV

V a Proband

VI

VII

Died at the age of 60

Vlll

IX

X

X I .m Fig. 2. Pedigree of the family with pseudoinflammatory dystrophy based on a follow-up study (1966-1989). Compared with our studies from 1980 (Forsius et al. 1982), a new affected subject, X,55, was noted. Two collateral cases, IX.21 and X,12, noted in 1980 as affected, have not progressed and are considered to have other fundus affections.

24 E R I K S S O N ET A L .

refraction starts later than the decrease of visual acuity (Fig. 4). There does not seem to be a good correlation between the decrease of visual acuity and the decrease of refraction. E.g. child nr. 5 already had bad visus before the age of 20, but his refraction was still the best among the eight sibs, only 4 diopters of myopia, at the age of 36.

The Nuclear Family Father. The father (VIII,13) of the eight affected children was examined ophthalmolo- gically for the first time at the age of 50, because he experienced a sudden decrease in the visual acuity of his left eye. At that time he had pigmented destructions and exudative areas in both fundi. At the age of 77 the visual acuity had decreased to counting fingers at 1 m in the right eye and at 30 cm in the left eye. Large atrophic retinochoroidal areas with pigmented scars all over the fundi, resembling choroiditis disseminata, were noted. The retinal arteries were attenuated (Fig. 5).

Mother. The mother, who was 16 years younger (VIII,27), had a visual acuity that was even more decreased than her husband’s (Fig. 3). The mother’s status could not be explained as myopic macular degeneration ( -7 D in both eyes) because a myopic conus was totally missing and no other signs of attenuated myopic changes were noted. In the macular area in both eyes large scars with glial formation were seen (Fig. 6) and there were some small pigmented flecks in the periphery. At the age of 60 the visual acuity was counting fingers at 20-30 cm in both eyes. At the age of 68 her refraction was - 15 D and choroidal atrophy was total in both eyes.

Grandchild TH. Female, born in 1963 (X,53) (former IV,6). Daughter of the oldest daughter in the nuclear family. She was investigated in 1978 and nothing remarkable was found. Since then strong myopia has developed and she uses contact lenses, -8.5 resp. - 8.0 D. She was investigated by us in

7 7d 7s

B

V.0c.a. for child n r . 7 V.oc.dx for child n r . 7 V.oc.sin for child n r . 7 MALE FEMALE

age in years

Fig. 3. Decrease of visual acuity in the affected parents (V111,13 and V11,27) and their affected children.

P S E U D O I N F L A M M A T 0 R Y FU N D U S D Y S T R O P H Y 25

8

7=child nr.7

1- -16

I,, I 10 20 30 110 50 70

age in years

Fig. 4. Spherical equivalent of refractions in diopters of the affected parents (V111,13 and V111.27) and their children. Myopia increases from puberty onwards by an average of almost -0.5 D per year.

1989. Visual acuity was 20125 with -9.0 D in both eyes. We also found a lightly pigmented eye fundus, and some small hyaloid bodies in the macular areas; A foveola reflex was seen. A few superficial small pigment flecks were noted in the periphery. With Goldmann’s three-mirror contact lens, it could be seen that the pigment layer in the extreme periphery was absent. This sign has also been observed in youngsters who later developed pseudoinff ammatory fundus dystrophy, which is why we noted her as suspect for the disease.

Child nr. 2. Female, born in 1944 (IX,49) (former 111,8). At the age of 15 her V~SUS, refraction and fovea were in both eyes. At the age of 20 the vision in her left

Flg. 5. Fundus of the propositus V111.13, father of the family with the eight affected children at the age of 65: large atrophic retinochoroidal areas were observed all over the fundi.

eye suddenly decreased to 0.1 but remained normal in the right eye (Fig. 3). At the age

26 E R I K S S O N E T A L

of 35, however, her visual acuity was only 0.1 in the right eye and counting fingers at 2.5 m and the myopia had progressed to - 6 D (Fig. 4). The scars caused by haemorrhages and exudates had also increased in size (Fig. 7A and B). Her daughter is the next case.

Grandchild R N . Female, born in 1964 (X,55) (former IV,8). In 1980 her vision was 25/20 without correction. The central areas in the fundi were normal. In the periphery above temporally in the fundus the pigment layer was uneven. In the right fundus below there were also ruptures in the pigment layer. No pigment at all covered the areas of the vor- ticous veins. We considered these changes to be within the normal range for a young fair child and did not note these findings as pathological (Forsius et al. 1982). In 1987, she had developed myopia of - 1.25 D in the right eye and -0.5 D with cyl. -0.5 DxO" in the left eye. When we saw her again in 1989 the visual acuity was finger counting 2-3 m with - 1.5 D in the right

Fig. 6. The right eye of the mother of the family (patient V111,27) at age 47. in the central area a large scar with glial formation was seen in the macula. There were some small pigment flecks in the periphery.

eye. In the fundus there was a large glial scar in the macula surrounded by small haemorrhages and colloid bodies. The visual acuity in the left eye was 20120 with a correction of - 1.0 D with cyl. -0.5 D x 180". The pigment layer in the macula was thin and very small pigmented rings with a light centre were observed. These looked like colloid bodies ophthalmosco-

A

Fig. 7. A. Case IX,49, born In 1944. Central area of the fundus of the right eye of a 22-year-old female with normal visual acuity and fovea. Above the fovea but closer to the optic nerve head. a deep retinal haemorrhage as the first sign of retinal dystrophy is seen. 6. The same fundus as in A, but 13 years later (in 1979) after several exaverbations with haemor- rhaglc episodes. The retinal pigment layer of the central fundus is severely destroyed. Some pigment disturbances are seen also outside the central area.

P S E U D O I N F L A M M A T 0 R Y F U N D U S D Y S T R O P H Y 27

pically but when seen with a biomicroscope through a contact lens their base was found to be flat. The pigment layer in the periphery was uneven, as if made up by microsco- pical spots. There was no doubt that this was a new typical case of pseudoinflammatory fundus dystrophy.

Child nr. 3. Male born in 1946 (IX,50). At the age of 19 there were no pathological findings. When he was 32 years old his vision was still ncjrmal but the refraction had decreased to - 6 D. Small nonspecific errors occurred in several pseudoisochromatic

Fig. 8. A. Fundus of the left eye of a 32-year-old male, 1x50. Late appearance of the fundus dystrophy in the foveal area where only a few colloid bodies (drusen) are seen. In the surroundings these drusen are more prominent. 8. Fluorescein angiography of the foveal area shows that the retinal pigment epi- thelium is uneven (grainy and thin).

plate tests. Dark adaptation was reduced by 3 log units. In the fundus white spots (hyaloid or colloid bodies) were seen (Fig. 8A) but they disappeared after a few years during the follow-up studies (this has also been seen in other members of the family). Fluor- escein angiography showed the retinal pigment layer to be definitely uneven (Fig. 8B).

Child nr. 5. Male, born in 1950 (IX,52). His visual acuity decreased bilaterally within a month (to 0.1 in the right eye and to 0.4 in the left eye) when he was only 13 years old. At the.age of 28 his visual acuity in the right eye was counting fingers and 0.1 in the left eye, but refraction had decreased to only about - 1.0 D in both eyes (Fig. 3 and 4). The fundi showed an advanced chorioretin- a1 destruction (Fig. 9).

Child nr. 7. Male, born 1954 (IX,54) (former III,13). We have followed his eye status since he was 11 years old when he was emmetro- pic and had a visual acuity of 20115 in both eyes. When he was 24 years old, the vision in his right eye suddenly decreased to 20140 with -2.0 D. There was a deep haemorrhage in the macular area and oedema in the retina above. The border of the oedematous

Fig. 9. Left eye of a 28-year-old male (lX.52) with severely atrophic areas throughout the eye ground.

28 E R I K S S O N E T A L .

area was coagulated with an argon laser several times, but without success and the eye finally went blind. He was listed among those affected with pseudoinflammatory dystrophy. In 1987 the vision in the left eye suddenly decreased. A Tyndall phenomenon was noted and he was treated for acute intis with dexamethasone and atropine. A week later he came to the hospital for a check-up and a secondary glaucoma in the iritic eye was noted. The application tonometer showed a tension of 15 mmHg in the right and 58 mmHg in the left eye. The tension did not go back to normal values with medi- cation, even after the inflammation in the eye had disappeared, and pilocarpin drops have been used since. The tension also rose in the blind eye. Trabeculoplasty was later performed in both eyes and the tension is under control with 2% pilocarpin drops x 3 in both eyes.

When we investigated him in 1989 the visual acuity in the right eye was finger counting at 40 cm with correction - 6 D

with cyl. +0.5 x 90 and in the left eye 251 20 with -7.5 D with cyl. -0.75 x 80. In the right fundus a large pigmented scar without elevation was seen. In the periphery some pigment flecks were noted in both eye grounds. The pigment layer was weakly developed. In the left central area small pigment points were seen together with some colloid bodies. No foveola reflex was seen; the fovea was dry and glistening.

Collateral Cases Male IX.21 (former IIZ,4). Cousin of the eight affected children, male, born in 193 1, was reported affected in 1982. He was the. nephew of the propositus, VIII,13 (11,7). When he was 36 years of age, the visual acuity of his left eye decreased to 20130. Fluorescein angiography disclosed an oedematous area in the macula close to the fovea with a leakage point. The diagnosis was choroiditis centralis serosa. The leakage point was photocoagulated and the area dried. In the right macula a few small pig-

Table 2

Refraction, visual acuity, and ultrasonographical length of the bulb of the eye in September 1989

Patient Right eye Lett eye

1x30 Child nr. 3: male, 43 y Refraction -9.5cyl- 0.5ax150° -7.Ocyl- 2.0ax70° Visual acuity 0.6 0.8 Eye ball length 23.3 mm 22.3 mm

Visual acuity 0.1 c.f. I m Eye ball length 24.7 rnm 24.9 mm

Refraction - 5 . 5 ~ ~ 1 - 1 .25ax0° - 5 . 5 ~ ~ 1 - 1 .25ax0°

Eye ball length 23.3 mm 23.6 rnm

Visual acuity 0.03 5.08 Eye ball length 24.7 mm 24.8 mm

1x31 Child nr. 4; male, 41 y Refraction -8.5cyl-1.0ax130° -9.0

IX,52 Child nr. 5; male, 39 y Visual acuity c.f. 113 m 0.12

1x33 Child nr. 6: female, 37 y Refraction - 15.5 - 16.5

IX,54 Child nr. 7; male, 35 y Refraction - 6.0 -9.Ocyl- 1.0ax9O0 Visual acuity c.f. 112 m 1 .o Eye ball length 24.1 mm 24.9 mm

IX.55 Child nr. 8: male, 34 y Refractlon - 7.75~~1- 0 . 7 5 ~ ~ 9 0 ~ - 8.25~~1- 0.5axl1Oo Visual acuity 1 .o 1 .o Eve ball leneth 24.1 24.8

c.f. 1 m=counting fingers at 1 rn.

P S E U D O I N F L A M M A T O R Y F U N D U S D Y S T R O P H Y 29

ment-free spots were seen. When we examined him in’ 1980, his visual acuity was 20/ 15 with +0.75 D in both eyes. There were small pigment defects in the retinal pigment layer in the central area, which included the photocoagulated point in both eyes. Many small pigment points and some small or large colloid bodies were present deeply within the retina in the extreme periphery. Some of them were surrounded by a pigment ring, but some pigmented rings occurred without hyaloid bodies. The most prominent degeneration was noted in the extreme periphery, as seen with Goldmann’s three-mirror lens.

In 1989, the visual acuity was corrected to 20/20 in both eyes. In the central fundi, scars in both eyes typical of serous retinopathy were seen. Outside these scars the pigment layer was even and of normal strength. In the midpenphery, quite a few small colloid bodies were observed. The extreme periphery had not changed since 1980. The peripheral changes resembled those seen in old people. The central lesions were typical “windows” in an otherwise normal pigment layer and they had not changed during the long observation time. Sorsby’s inflammatory dystrophy as well as serous retinopathy led to leakage through a defective pigment layer from the choroid to the retina. In 1980 we therefore thought it natural, though after some hesitation, to place him among those affected. In the follow-up study no progression has taken place as it has in all the other affected, which is why we may conclude that he is not affected with pseudoinflammatory fundus dystrophy.

Female X.12 (former IW). The child of a niece of the proband, a female born in 1945. The visual acuity in her right eye suddenly decreased in 1979. The refraction was em- metropic. There was a dark elevation in the right fundus between the macula and pa- pilla, and the retinal layer above and lateral

to the elevation was oedematous. Mela- noma in the choroid was suspected. The retinal periphery in both eyes was normal as well as the pigment layer in the left eye. The clinical course was unchanged 10 months later, and a diagnosis of pseudoinflammatory dystrophy was discussed at the time when our article appeared, and she was marked as affected in the pedigree. How- ever, the protrusion later increased in size and an enucleation was performed in 1983. The diagnosis from the pathological department was,melanoma of a mixed type. All further discussion of her diagnosis was stop- ped and in the new pedigree (Fig. 2) she is marked unaffected.

We also studied other children of the eight affected sibs and many other relatives. Nothing noteworthy was found in any of them.

Length of the Bulb of the Eye In September 1989 we had the opportunity to study the six youngest children of the affected family again. The visual acuity and refraction were noted (Table 2) and no remarkable change had occurred. Also the length of the eyes was recorded ultrasono- graphically and, as a mean, the bulb length is longer than normal. We have not been able to follow with ultrasonography the same subjects during the development of their myopia. Two of the affected children (nr. 3 and nr. 7) have anisometropia of 1.75 D resp. 3.5 D. The difference in axial length is 1.0 resp. 0.8 mm for these subjects, show- ing that the myopia is axial, or at least partly. There is no correlation between the visual acuity and the degree of myopia, and also not between bulb length, myopia, and age in the investigated siblings.

Discussion

In 1940 and 1949, Sorsby and collaborators described an autosomal, dominantly in-

30 E R I K S S O N E T A L .

herited disease with bilateral haemorrhages and exudates in the central fundi as the most prominent features. The disease is now known as Sorsby’s macular pseudoinflammatory dystrophy. The disease starts to ap- pear when the patient is about 40 years old and follows a slowly progressive course. The first symptoms are retinal lesion with oedema, haemorrhages, and exudates in the macular area. Later there is considerable scarring, with sclerosis in the choroidal ves- sels associated with pigmentary prolifer- ation. Some months or years later, the other eye develops the same symptoms. The ter- minal stage, reached after 20-30 years, is characterized by a more or less uniform, widespread atrophy of the choroid with some pigmentation. Most families published afterwards show the same autosomally dominant mode of heredity.

Later Babel et al. (1982) presented a large family with an exudative type of dystrophy. In this family haemorrhages were rare and colloid bodies dominated the clinical picture. In most of the affected, symptoms appeared at about the age of 40. The disease was autosomally dominantly inherited.

Recently Dreyer & Hidayat (1988) presented a family with a dominantly inherited macular dystrophy. Histologically retinal pigment epithelial atrophy was found and varying degrees of pigment epithelial meta- plasia. In most of the patients, visual prob- lems appeared around the age of 40 or later. No haemorrhages were seen in this disorder, which was considered to be distinct from other pseudoinflammatory fundus dystrophies earlier described.

Autosomal recessive inheritance has also been suggested. Sorsby (1940) presented two children, 8 and 12 years old at the onset of the disease, whose parents were first cou- sins, and Francois (1961) noted two brothers of 41 and 37 years old who he thought probably showed autosomal recessive inheritance. Frank and collaborators

(1974) described a new autosomally dominantly inherited type of dystrophy where colloid bodies dominated the expression, but it was expressed in the first decade of life already. Our follow-up study performed in

1982-1989 resulted in the conclusion that two of the people we had, with hesitation, earlier considered to be probably affected, have not shown progression and therefore have now been treated as not affected (IX,21 and X,12). On the other hand, one female (X,55), earlier considered by us as probably normal at the age of 16, had typical pseudoinflammatory fundus dystrophy 8 years later. Also a slight myopia had developed. Another female (X,53), now aged 25, has developed strong myopia but shows no convincing fundus changes. We consider her as suspect. Both are daughters of affected subjects. The new case (X,55) is the daughter of IX,49. Her father was born in a different region (Carelia), and he is the only parent of affected subjects who was born outside the until recently isolated parish of Lavia in south-western Finland.

Our extended genealogical studies have demonstrated that the grandparents and the parents of all eight affected children were related in many different ways. Among more than 70 ophthalmogenetically investigated collaterals (mainly in generations VIII-X), only one subject, a sister of the mother of the eight affected children, has been definitely found to have fundus dystrophy. Only three out of 23 sibs in generation VIII were affected, in spite of the fact that only four of these had not reached the age for the manifestation of the Lavia-type of fundus dystrophy.

An autosomal dominant inheritance with irregular or low penetrance, like that described by Francois (1961), could explain why so few affected subjects were found among collaterals and in ancestral lines of this family. This type of heredity could also

P S E U DO1 N F L A M M A T O R Y F U N D U S D Y S T R O P H Y 31

explain the asymmetric changes of visual acuity and refraction, apparent without longitudinal studies, and why some of the eight affected sibs, being homozygotes, developed the fundus dystrophy early and in a severe form. However, it is difficult to explain why all eight sibs are affected while so few others are affected both in the as- cending and descending lines.

In the church archives in Sweden and Fin- land, and particularly in the parish books, there are remarks on the ability of people to read and any physical defects, such as poor sight and blindness, are noted (Eriksson et al. 1973). However, in ourex- tensive archive studies in Lavia, we have been able to find only one male (V,1) noted as having bad vision at the age of 10 (Fig. 2). The lack of blindness or poor sight in earlier and recent generations argues against dominant inheritance. Many people of the last generation are already of the age to be affected, but only one has the disease so far. We suggest that the family shouid be followed for another generation. After that, the mode of inheritance of this pseudo-inflammatory fundus dystrophy may be better evaluated.

The above-mentioned four cases described by Sorsby (1940) and FranCois (1961) may be of the same type of fundus dystrophy as the Finnish one and they are the only one described outside Finland so far. It will be of interest to see if the gene responsible for this fundus dystrophy shows a similar enrichment in the Finnish population, as is the case with about 30 other rare recessive disorders.

Epilogue Our studies of this rare hereditary eye fundus dystrophy demonstrate the heuristic value of longitudinal studies of unusual and progressive familial disorders. If we had published this family after our first in-

vestigation in the 1960s, only the mother and three of her eight children would have been classified as affected by the same hereditary disorder, i.e. as an autosomal dominant fundus dystrophy. Particularly “rare” progressive genetic disorders, with a late or varying manifestation age, demonstrate the importance of follow-up studies and the need for courage in correcting one’s own diagnoses.

Acknowledgements

Partly based on a paper presented at the symposium on Impact of Medical Genetics on Public HeaIth at the 50 years’ Anniver- sary of the Institute of Medical Genetics, Copenhagen, October 27-30, 1988.

References

Babel, J. , E. Cabernard, D. Klein, S. Korol, H. Krluchi & P. Schafroth (1982). Pseudo-inflammatory chorioretinal degeneration of the posterior pole. Graefe’s Arch. Clin. Exp. Ophthalmol. 219, 236251.

Carr, R. E., K. G. Noble & I. Nasaduke (1977). Pseudoinflammatory macular dystrophy. Trans. Am. Ophthalmol. SOC. 15, 255-271.

Dreyer, R. F. & A. A. Hidayat (1988). Pseudo- inflammatory macular dystrophy. Am. J . Ophthalmol. 106, 154-161.

Eriksson, A. W., M.-R. Eskola, J. Fellman & H. Forsius (1973). The value of genealogical data in population studies in Sweden and Finland. In Genetic Structure of Populations, N. E . Morton (ed.). Honolulu, Univ. Press of Hawaii, pp. 102-1 18.

Forsius, H. R. & A. W. Eriksson (1980). Reti- noschisis X-chromosomalis. In Population Structure and Genetic Disorders. A. W. Eriksson, H. R. Forsius, H. R. Nevanlinna, P. L. Workman & R. K. Norio (eds.). Lon- don, Academic Press.

Forsius, H. R., A. W. Eriksson, E. A. Suvan- to & H. I. Alanko (1982). Pseudoinflammato- ry fundus dystrophy with autosomal recessive inheritance. Am. J. Ophthalmol. 94, 634- 649.

FranGois, J. (1961). Heredity in Ophthalmology. St. Louis, C. V. Mosby, p. 475.

32 E R I K S S O N ET A L

Frank, H. R., M. B. Landers, R. J. Williams & J. B. Sidbury (1974). A new dominant progressive foveal dystrophy. Am. J. Ophthalmol.

Hoskin, A., K. Sehmi & A. C. Bird (1981). Sorsby's pseudoinflammatory macular dystrophy. Br. J. Ophthalmol. 65, 859- 865.

Sorsby, A. (1940). The dystrophies of the macula. Br. J. Ophthalmol. 24, 469-529.

Sorsby, A., M. E. Joll-Mason & N. Gardener (1949). A fundus dystrophy with unusual features. Br. J. Ophthalmol. 33, 67-97.

78, 903-9 16.

Vainio-Mattila, B., A. W. Eriksson & H. For- sius (1 969). X-chromosomal recessive retinoschisis in the region of Pori. Acta Ophthal- mol. 47, 1135-1 148.

Address: Prof. Dr. A. W Eriksson Institute of Human Genetics MedicaI Faculty Free University Van der Boechorststraat 7 1081 BT Amsterdam The Netherlands

Documents

Pseudoinflammatory fundus dystrophy: a follow-up study