Clinical Genetics 1913: 4: 301-310 Congenital cornea plana in Finland A. W. ERIKSSON,W. LEHMANN,AND H. FORSIUS Folkhalsan Institute of Genetics, Population Genetics Unit, Helsinki; Institute of Human Genetics, University of Kiel, Kiel; University of Oulu Eye Hospital, Oulu, Finland Two different hereditary forms of congenital cornea plana are described: an autosomal dominant form with relatively mild symptoms, and an autosomal recessive form (CPCR) with more severe symptoms, such as decreased visual acuity, extreme hyperopia (total refraction usually 10 D or more), hazy limbus corneae, more or less pronounced opacities in the corneal parenchyma, and marked arcus senilk, often detectable at an early age. As far as can be judged from the number of cases hitherto published, cornea plana is a rare disease. In Finland, 49 caw of the recessive and seven of the dominant form of cornea plana congenita have been discovered to date, which is about twice the number of cases of recessively inherited cornea plana reported elsewhere in the world. In Finnish Lapland, the gene frequency of cornea plana congenita recessiva is estimated to be 1.3 (about 16 patients per 100,000 inhabi- tants), or about four times as high as in Finland as a whole. Around the lower reaches of the River Kemijoki there is a relatively high prevalence of the recessive form of the disease. The Kemijoki pedigree includes 25 patients related to each other through their ancestors. Accepted for publication 31 Junuury 1973 The descriptive name cornea plana does not Rudiments of a corneal limbus appear at the quite correspond to the ocular findings in end of the second month (fetal length 25-30 the disease in question. The cornea is not mm), but a difference in curvature between flat, but its radius is larger than normal and the cornea and sclera only becomes discern- involves a continuation of the curved sur- ible during the third month (fetal length face of the sclera over the area of the 45-50 mm), and the borderline between cornea. these two tissues is not distinct until the end Congenital cornea plana seems to be a of the third month (fetal length 65 mm). The rare anomaly. Only one to three cases are development of the angle of the anterior described in most reports. If more or less chamber is considerably slower. This struc- the same phenotype can be caused by ture does not attain its final shape until after both a recessive and a dominant gene, the birth. It can thus be concluded that the phenotype caused by the dominant gene is gene causing cornea plana influences devel- generally manifested by milder symptoms. opment in the 12th embryonic week, when This applies also to cornea plana. the bulb is attaining its final shape. In this disease, the corneal anlage deviates from the normal, as is also proved by the thinness of Pathogenesis the cornea and the differences in thickness The first rudiments of a cornea can be dis- between its various portions. In many in- tinguished in the fourth to fifth embryonic stances fibers run from the iris into the cen- weeks, when the embryo measures 7-9 mm. tral portion of the cornea. By contrast, the 3 02 ERIKSSON, LEHMANN, AND FORSIUS iridocorneal angle is usually normal, in spite of a low anterior chamber, and increased intraocular pressure is not typically asso-> ciated with cornea plana, although it does occur. The corneal tissue is derived from both the mesoderm and the ectoderm. Hence, pathological changes in the limbus and cornea may theoretically originate in both of these structures. Abnormal flatness of the cornea also occurs in connection with devel- opmental disturbances of a different genesis. A lengthened sclerocorneal zone and slight flatness of the cornea are often seen in cases of aniridia, for instance. In patients with coloboma uveae the cornea is sometimes not only unusually small, but also flat. Corneal flatness has been reported in Hurler’s dis- ease, Lobstein’s syndrome and DI trisomy (FranGois 1965). The mode of inheritance varies. Severe inflammation of the cornea and sclera may also cause flattening of the cornea. Clinical Picture As a rule, cornea plana congenita recessiva (CPCR) is readily identified by the following typical signs: Fig. lb. Slit lamp photograph of the anterior portion of one eye of the patient shown in Fig. 1. The ante- rior chamber is extremely flat and the pupil is dis- located. I) The sclerocorneal zone is lengthened, which results in superficial haziness of a broad area in the limbus. The borderline between the sclera and cornea is indistinct. The cornea is either seemingly or actually unusually small (Figs. 1 a and 2).Arcus senilis often occurs at an early age. 2) A round grey area, about 5 mm broad, is seen centrally in the cornea (Figs. la and 2). The cornea is thin at the margin of this area and thicker at the middle (Figs. lb and FIg. la. Left eye of an 11-year-old boy wlth recessive 2). The parenchyma of this disc-shaped cen- congenital cornea plana (case 18). His mother (case 13) also has cornea plana. tral area is more opaque than in other sites. CONGENITAL CORNEA PLANA IN FINLAND 303 Fig. 2. Extreme arcus senilis in the left eye of a 67-year-old female (case 30) with congenital cornea plana. 3) The corneal radius is larger than nor- 4) The cornea is thinner than normal. mal. The anterior portion of the eye (cor- 5) The eyelid often droops slightly (Fig. nea) is therefore less prominent or forward 3). bulging than normal when seen from the Minor differences in the clinical picture side (Figs. lb and 2). occur between the two eyes of the same subject and between different members of the same family. In mild cases, visual acuity is 0.6-0.8. In severe cases other anomalies of the bulb are also present, such as mal- formations of the iris, a slit-like pupil, or adhesions between the iris and cornea. Ab- sence of the lens has been described, and blindness sometimes occurs. In our series of 49 cases of recessive cornea plana, three patients were blind. Material and Results Forsius discovered the first cases of cornea plana in Finland in 1953, when practicing Fig. 3. Slight ptosis palpebrae congenita is often as- sociated with cornea plana. as an ophthalmologist at Kemi in Finnish 3 04 ERIKSSON, LEHMANN, AND FORSIUS I tected in two families. Patients with the el709 milder, dominant form do not exhibit the central opacity of the cornea which is typical ep of patients with the recessive form. Corneal refraction deviates from the normal by only 5-8 D. Both of the above-mentioned fami- lies have many ancestors traceable to the rural community of Jalasjarvi, in the west of central Finland, and we have recently suc- ceeded in proving that the two families have some common ancestors (Fig. 4). Families showing the dominant form of cornea plana have previously been described by Waarden- burg (1930), Barkan & Borley (1936), Ga- CORNEA PLANA (DOMINANT) steiger (1945) and Larsen & Eriksen (1949). Recessive form. Recessively inherited cor- nea plana has been observed by us in a B50 BLIND AT 50 total of 49 subjects in 32 sibships. Corneal refraction varies widely. The lowest reading for corneal refraction is 23 D, and values under 34 D predominate. A few members of these families have a nearly normal corneal refraction. These subjects are marked in the pedigrees as cases of CPCR if the cornea shows other typical signs. Although patients with cornea plana were sought in Helsinki in 1953-63 just as actively as in Oulu from Fig. 4. Pedigree of two families with the dominant 1964 onwards, only eight patients with form of cornea plana. CPCR, belonging to seven different families, have been found south of the County of Lapland. Since then, he has systematically Oulu; the remaining 41 patients trace their recorded such cases when they occurred origin to north Finland. The geographical among his private patients at the Ophthal- distribution of the cases and their parents mological Department of Helsinki Univer- suggests that the frequency of the CPCR sity Central Hospital and, later, at the Eye gene is much higher in north Finland than Department of Oulu University. Through the in the south (Fig. 5). courtesy of colleagues we have obtained No symptoms or signs have been ob- data on additional families affected with this served in the parents of our patients with disease. Our results have been published in CPCR. An exception to this rule is the a number of reports (Forsius 1961, Forsius second family from the left in the pedigree & Lehmann 1962, Forsius & von Fieandt in Fig. 6 (Family Meh.), which includes two 1963, Forsius & Eriksson 1972). At present cases (17 and 18) in which CPCR is present our material consists of 34 sibships com- in the mother and two children. It seems prising 56 cases of cornea plana. probable, however, that the father also has Dominant form. Seven cases of the domi- the CPCR allele. The father comes from nant form of cornea plana have been de- another community than the mother, but CONGENITAL CORNEA PLANA IN FINLAND 3 05 , , > /, ,. 2, 1 2. 2-3 't I, ~~ ~- j. TILASTOKARTTA eC0RNEAPLANA CUNGENITA RECESSIVA ICPC Rl ns1BsHIPs 0 @PARENTS OF CPCR PATIENTS L Jl ,,P? w ..........,.."" .......... ....~ ............................ U.S.S.R. ERIKSSON, LEHMANN, AND FORSIUS 8 n n U 0- ~ 5 5 x x CONGENITAL CORNEA PLANA IN FINLAND 307 his paternal grandfather had the same sur- JACOB name and came from the same village as I 4'.-1698 -1702 one of the ancestors of family Hei.