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Three generations of a family with Rieger's syndrome are presented. Ocular and dental abnormalities constitute the major manifestations. Hypodontia, microdontia, enamel hypoplasia, missing teeth, peg-shaped teeth, and malocclusion are frequent oral findings. Hypoplasia of the maxilla causes the mandible to appear prominent, giving the patient a prognathic appearance. Aniridia, hypoplastic iris, and glaucoma are the major eye problems. The propositus also has short stature and decreased growth hormone levels which have not been reported before in this syndrome. The importance of early diagnosis is stressed in order to preserve the remaining dentition by proper dental care and to be aware of the possibility of the presence of glaucoma, which should be treated as soon as discovered.

In 1931 Marinesco et al1reported a family in which five siblings, four boys and a girl, had cerebellar ataxia and oligophrenia with congenital cataracts. In 1947 Sjogren2reported two patients in two different families, both with consanguineous parents, who had cerebellar ataxia, oligophrenia, and congenital cataracts. Since that time the syndrome of cerebellar ataxia, oligophrenia, and congenital cataracts has become known as the Marinesco-Sjogren syndrome. It is a very rare syndrome apparently inherited as an autosomal recessive trait. Other authors who have written papers on this syndrome are Richards,3Garland and Moorhouse,4Decock and Macken,5Durusken,6MacGillivray,7Dogulu and Mutler,8Dureaux, Cordier, Ziza and Tridon,9Amyot,10Franceschetti, Marty, and Klein,11Muller,12Alter, Talbert, and Croffead,13,14and Prot.15Francois16states that aniridia with oligophrenia has been reported several times. It is the purpose of this

Penetrating keratoplasty in aphakic eyes is indicated most frequently in cases of corneal edema of varying degree following cataract extraction. This edema may appear as an aggravation of a preexisting endothelial-epithelial (Fuchs') dystrophy of the cornea, or as a consequence of endothelial damage from a complicated cataract extraction or later impaction of vitreous against the endothelium. Other indications in aphakic eyes have been corneal edema resulting from chronic uveitis, opacity due to explosion or chemical injuries, opacified corneal grafts, opacity associated with familial aniridia and various degenerations. Lamellar transplants seldom achieve satisfactory therapeutic and visual results in most of these because the underlying disease is in the endothelium. Since the early days of corneal transplantation aphakia has been considered a very unfavorable condition for penetrating keratoplasty, and the results of keratoplasty in aphakic eyes have, until recently, been reported as very poor. In the panel discussion of keratoplasty of the

Among 28 children under 4 years of age hospitalized with congenital aniridia, Wilms' tumor subsequently developed in six and one had the neoplasm on admission. Five of these seven patients have not, to our knowledge, been reported previously, bringing to 22 the total number of cases known with this association. Although one child in our series had familial aniridia, all other cases of aniridia with Wilms' tumor have been sporadic, suggesting that the two disorders originate by common or concurrent gene mutation or by environmental effects on embryogenesis. The aniridia-Wilms' tumor complex includes an array of nonocular anomalies, providing further evidence that the neoplasm is but one manifestation of a distinctive syndrome.

Introduction This paper reports a series of observations made during the past 2 years in patients with aniridia. This condition is familial, and the transmission is dominant by an autosomal gene. It demonstrates high penetrance and variable expression. Visual acuity was less than 20/100 in 86% of aniridic eyes, as tabulated from the literature 1,2 plus my own few cases (Fig. 1). Aniridia, therefore, represents an important medical and surgical problem to the ophthalmologist and a social challenge to the community. Aniridia is characterized by reduction of the iris, and in the complete case the iris rudiment is visible only when the anterior chamber angle is examined with slit lamp or gonioscope. In modified cases the iris may be regionally deficient. Associated with the iris defects are persistence of pupillary membrane and of the tunica vasculosa lentis. Cataract and displacement of the lens may

Extract: Study was made of the death certificates for all 29,457 children under 15 years of age who died of cancer in the United States during 1960–1966. Congenital defects were greatly underreported, but from the anomalies that were recorded, some new understanding of the relation between oncogenesis and teratogenesis may be derived. On 146 death certificates, Down's syndrome was listed with leukemia, an 11-fold excess over normal expectation. The peak mortality occurred at two years of age. In the general population, the peak occurs two years later and is due to an increase in the rates for acute lymphocytic leukemia. This study and others indicate that, contrary to popular opinion, myelogenous leukemia is not significantly more common than usual in Down's syndrome. The association of Wilms' tumor with aniridia or renal anomalies, unknown when the death certificates were made out, was nevertheless apparent. There were previously unreported cases of leukemia with osteogenesis imperfecta, Marfan's syndrome, Treacher-Collins syndrome, and Ollier's syndrome. These cases, and others described in the literature, raise the possibility that certain genetically induced disorders of bone or connective tissue may predispose to leukemia. There were also four new cases of leukemia-lymphoma with immunological abnormality (two with myasthenia gravis; one each with ataxia-telangiectasia and agammaglobulinemia), and two with leukemia and congenital granulocytic abnormalities (one each with agranulocytosis and familial granulomatosis). Other concurrences of possible etiologic significance included two of phenylketonuria and leukemia-lymphoma, three of tetralogy of Fallot and glioma and one of cleidocranial dysostosis and medulloblastoma. Clarification of these relations may come from studies of susceptibility to viral transformation in vitro of skin fibroblasts from children with the anomalies noted above. This study indicates that greater accuracy and completeness in filling out death certificates would greatly aid research and the clinical benefits derived from it. Speculation: Although imperfect, diagnoses recorded on death certificates may provide clues to as yet unknown relations between cancer and congenital defects.

GLAUCOMA is often associated with aniridia (irideremia). On clinical examination the iris appears totally absent, but histologically a narrow rim of iris of varying width and some persistent mesodermal tissue in the angle have been found in all cases. In many the pigment epithelium overlaps the stump of the iris, as in an ectropion. According to Parsons,1the stump of iris is often adherent to the sclera at the extreme limit of the anterior chamber over a considerable portion of the circumference; part of the angle is usually open, and through this efficient filtration is maintained until some intercurrent cause leads to obliteration. It is believed that the imperfect separation of the iris from the cornea at the periphery is due to arrested development. Recently Callahan2reported histologic findings in a case of aniridia with a rudimentary iris, which varied slightly in size but was about 1 mm.

Aniridia is a congenital absence of the iris. Complete aniridia is more often apparent than real, for if sections are made through an eye that appears to possess no iris, apron-like vestiges of iris tissue will usually be found projecting a short distance from the ciliary attachment of the root of the iris. They are feebly expressed and are so rudimentary that the most careful macroscopic examination will usually fail to reveal the presence of vestiges of iris. The most common embryologic defects of the eye are those of the iris and the pupil. The iris does not begin to grow until after the lens is ensheathed with the hyaloid vascular membrane, at which time it is in contact with the forming cornea. The edge of the secondary optic vesicle must now force itself between the fibrovascular sheath and the lens. The branches of the ciliary vessels which anastomose

In 1964, Miller et al reported the results of an epidemiologic study of patients with a common form of renal cancer in childhood known as Wilms' tumor.1These authors reviewed the medical charts of all patients with Wilms' tumor, listed in the diagnostic files of six hospitals, which had been diagnosed between January 1940 and July 1963. The charts reviewed were from the Children's Hospital in Boston (184 cases), Memorial Hospital in New York (103 cases), Children's Hospital in Los Angeles (87 cases), Children's Hospital of Washington (29 cases), the University of Michigan Medical Center (25 cases) and from the National Institutes of Health Clinical Center (25 cases). These records were carefully reviewed to determine the presence of associated congenital defects in children with known Wilms' tumors. This study confirmed the excessive concurrence of certain congenital defects with Wilms' tumor. For example, three of the children had hemihypertrophy, establishing

Aim: To determine the range and distribution of central corneal thickness in patients with aniridia and compare with age- and sex-matched controls.Methods: This was a prospective cross-sectional observational case-control study performed at a tertiary eyecare hospital. All patients diagnosed with aniridia from June 2006 to April 2008 were enrolled. Patients were excluded if they had corneal oedema, central corneal scars, central aniridic keratopathy, or any history or signs suggestive of previous surgery or injury. Central corneal thickness was measured by ultrasoundpachymetry and the mean of 5 measurements per eye was used as the study measurement. The results were compared with those of age- and sex-matched controls.Results: The mean central corneal thickness in the aniridia group was 0.603 mm compared with 0.566 mm in the control group (p = 0.0083).Conclusions: This study has determined the range and distribution of CCT in Indian patients with aniridia and substantiates the fact that patients with aniridia in an Indian cohort also have significantly thicker corneas. This needs to be considered for making accurate IOP measurements in these patients to ascertain the appropriate management.

It is not the intention of this presentation to discuss in detail the embryology, histology, or genetics of congenital aniridia or irideremia. These phases of the subject have been ably and recently covered by Callahan and Pincus. Congenital lack of the iris is always represented by a narrow rim of tis­ sue, is always bilateral, and results from defects in the development of the mesodermal and epidermal layers of the iris. It shows a marked tendency to hereditary transmission and occurs usually as a dominant character­ istic. Aniridia is generally complicated by other structural defects of the eye, such as cataract, ectopia lentis, nystagmus, corneal opacities, aplasia of the macula, and es­ pecially by glaucoma. It is impossible to determine exactly how frequently congenital aniridia occurs, per­ haps in 0.04 percent of cases. Judging, how­ ever, from the small number of cases seen by clinicians of wide experience, the disease is comparatively rare. What proportion of these patients develop glaucoma is even more diffi­ cult to determine, but it is certainly a fairly frequent complication of an already un­ pleasant picture. According to E. Treacher Collins

A chromosome translocation, t(8p + ; 11q -), in a patient with aniridia and Wilms' tumor, appeared balanced by standard techniques, including trypsin banding. Computer analysis of optical microscope scanning profiles of chromosome pairs 8 and 11 revealed an interstitial deletion of the short arm of 8. Computer analysis coupled to the new banding techniques provides greater resolution for the detection of subtle chromosomal variations not recognized by banding methods alone.

The Meckel syndrome is a genetically determined (autosomal recessive) disease with major developmental abnormalities incompatible with life. The ocular manifestations include cryptophthalmos, clinical anophthalmos, microphthalmos, sclerocornea, microcornea, abnormal iridocorneal angle, partial aniridia, cataract, persistent tunica vasculosa lentis, retinal dysplasia, posterior staphyloma, and hypoplasia of the optic nerve. The ocular abnormalities are very similar to those of the 13-15 trisomy syndrome, but the chromosome karyotype is normal in the Meckel syndrome.

WILMS'S tumor, one of the most common abdominal neoplasms of childhood, has been reported to be associated with certain congenital anomalies. Miller et al1of the National Institute of Health, reviewed a series of 440 cases of Wilms's tumor in association with aniridia, hemihypertrophy, pigmented nevi and hemangiomas, hypospadias, cryptorchidism, horseshoe kidney, and duplication of the upper urinary tract. The more common anomalies associated with aniridia and Wilms's tumor, and the cases reported in the literature, are noted in the Table. A survey by Miller1indicates that only six cases of Wilms's tumor have been reported having aniridia as one of the associated congenital anomalies. The presence of Wilms's tumor with aniridia, cataracts, recurved pinna of the ear, and duplication of the upper urinary tract has occurred in one of our patients. A diagnosis of Wilms's tumor should be suspected and considered in the differential diagnosis when a

1. Drash, A., Sherman, F., Hartmann, W. H., and Blizzard, R. M.: A syndrome of pseudohermaphroditism, Wilms' tumor, hypertension, and degenerative renal disease, J. P~DIAT. 76: 585, 1970. 2. Frasier, S. D., Bashore, R. A., and Mosier, H. D.: Gonadoblastoma associated with pure gonadaI dysgenesis in monozygous twins, J. PEDIAT. 64: 740, 1964. 3, Grupe, W. E., Cuppage, F. E., and Iteymann, W.: Congenital nephrotic syndrome with interstitial nephritis, Amer. J. Dis. Child. 111: 482, 1966. 4. Denys, P., Malvaux, P., Van Den Berghe, H., Tanghe, W., and Proesmans, W.: De pseudohermaphrodisme masculin, d'une tumeur de Wilms, d'une nephropathle parenchymateuse et d'un mosaicisme XX/XY, Arch. Franc. Pediat. 24: 729, 1967. 5. Raubltschek, H.: l~ber eine b~isartlge Nieren gesehwulst bei einem kindlichen Hermaphroditen, Frankfurt Z. Path. 10: 206, 1912. 6. Stump, T. A., and Garrett, R. A.: Bilateral Wilms' tumor in a male pseudohermaphrodite, J. Urol. 72: 1146, 1954. 7. AngstrSm, T.: Nephroblastoma in a case of agonadism, Cancer 18: 857, 1965. 8. Di George, A. M., and Harley, R. D.: The association of aniridia, Witms' tumor and genital abnormalities, Arch. Ophthal. 75: 796, 1966. 9. Smith, N. J.: Glomerulonephritis, Wilms' tumor and horseshoe kidney in an infant, Arch. Path. 42: 549, 1946. 10. Zunin, C., and Soave, F.: Association of nephrotic syndrome and nephroblastoma in siblings, Ann. Paediat, 203: 29, 1964. 11. Lines, D. R.: Nephrotic syndrome and nephroblastoma. Report of a case, J. P~DIAT. 72: 264, 1968. 12. Gilbert, J. B.: Studies in malignant testis tumors. VIII. Tumors in pseudohermaphrodites: Review of sixty cases and a case report, J. Urol. 48: 665, 1942. 13. Scully, R. E.: Gonadoblastoma. A review of 74 cases, Cancer 25: 1340, 1970.

OSTEOGENESIS imperfecta congenita (Vrolik) is usually a hereditary disease. It is characterized by fragility of bones, so-called blue sclerae, otosclerosis and deafness, relaxation of ligaments and skeletal muscles, dental defects, and other deficiencies related to mesodermal tissues. It is known variously by such names as Lobstein's syndrome, osteopsathyrosis idiopathica, and van der Hoeve's disease. HISTORICAL REVIEW Ekmann, in 1788, carefully described the disease in three generations of patients. He did not mention blue sclerae and deafness. Subsequent to this report cases of multiple fractures were described by Lobstein, Vrolik, and others. Thin sclerae were described by Henzschel, 1 in 1831, in a female with aniridia. Gescheidt, 2 in 1832, described blue sclerae in a case of microphthalmos. Neither author noted a familial tendency or other associated characteristics of the disease. In 1841 von Ammon, 3 without the aid of magnification, noted the thinness of the sclera in dissected eyes and

WHEN, through epidemiologic study of persons or families, diseases are found to be associated, the opportunities for determining their etiology may be very much increased. The association of leukem...

The syndrome of Wilms' tumor associated with aniridia consists of congenital nonfamilial aniridia, Wilms' tumor developing before 3 years of age, eye lesions associated with aniridia, mental and growth retardation, microcephaly, genitourinary anomalies, and deformities of the pinna. The twenty-fifth case of this syndrome is presented and demonstrates new findings not seen previously: congenital lipoma and spina bifida with meningocele. This case provides an important link between the Wilms' tumor-aniridia syndrome and disorders of growth control (hemihypertrophy, hamartoma, and visceral cytomegaly syndrome). The array of overlapping congenital malformations occurring with Wilms' tumor, aniridia, and disorders of growth control suggest common teratogenic and oncogenic mechanisms.

Numerous congenital malformations consisting of aniridia, hypertelorism, bilateral webbing of the cubital and the popliteal regions and bilateral cryptorchidism were documented in a phenotypic male infant. Severe mental retardation, bilateral cataracts, exophthalmia and glaucoma followed by complete blindness were noted by the time the child was 9 1/2 years of age. Leukocyte and fibroblast cultures were reported to show two cell lines, a majority of the cells showing a 47, XXY complement and a minority showing a 48, XXXY complement.

The electrooculogram (EOG) is a useful electrophysiological test of retinal function. We have previously described (Reeser, Weinstein et al., 1970) our experience with this measurement, and have noted that abnormally high light: dark ratios (>4.0) had been recorded in certain individuals. These individuals were some of those studied with aniridia (congenital absence of the iris) or albinism (generalized or ocular).