Rufus O. Howard

Retinoblastoma and chromosome abnormality. Partial deletion of the long arm of chromosome 13.

A 7-year-old girl with retarded physical and mental development was found, on chromosome determination, to have deletion of a segment of the long arm of chromosome 13 (13 q—). A precise chromosome identification was made on peripheral leukocytes by using a quinacrine banding technique. Because of previous reports of an association of the 13 q—chromosomal abnormality with retinoblastoma, an ophthalmologic examination was carried out. The patient was found to have bilateral microphthalmia, and multifocal, moderately well-differentiated retinoblastoma in the left eye.

Ocular findings in triploidy.

We studied the abnormal ocular and systemic findings in one case of true triploidy and two cases of triploid mosaicism. A liveborn triploid child 69,XXY, had abnormalities including cebocephaly, a single midline nostril, incomplete cleft palate, transverse palmar creases, partial syndactyly, and ambiguous genitalia. Ocular abnormalities included hypotelorism, blepharophimosis, microcornia, iris coloboma, cataract, persistent hyaloid vasculature, retinal dysplasia, and optic atrophy. A 16-year-old girl with triploid mosaicism had congenital left facial and body hemiatrophy, both growth and mental retardation, left-sided grand mal seizures, incontinentia pigmenti of both legs, partial syndactyly, and generalized weakness. Results of her ocular examination were within normal limits. A 13-year-old boy with triploid mosaicism exhibited both growth and mental retardation, truncal obesity, and required a brace to support his back. Ocular findings included synophrys, bilateral blepharoptosis, and abnormal results of Schirmer tear test. Studies indicate a wide spectrum of ocular and systemic abnormalities occur that are presumably associated with the chromosome error.

Ophthalmic Features of Chromosome Deletion 4p-(Wolf-Hirschhorn Syndrome)

By using the Giemsa banding technique we identified three patients with chromosome deletion 4p-. All had anterior segment anomalies, exotropia, blepharoptosis, antimongoloid palpebral fissures, hypertelorism, and disk abnormalities. One patient (Case 1) had Riegers anomaly. Some clinical features in patients with 4p- are similar to those in patients with chromosome deletion 5p-, cri-du-chat syndrome, although 4p- individuals do not have the distinctive cry. The ocular features which distinguish 4p- from other deletions include normal tearing, some degree of blepharoptosis, and the preponderance of anterior segment signs.

Human Retinal Dysplasia

We studied the ultrastructure of the four types of dysplastic rosettes and compared them with retinoblastoma rosettes. Dysplastic rosettes have morphologic characteristics intermediate between the normal photoreceptor layer and retino-blastoma rosettes; Müller cells contribute to the formation of dysplastic but not neoplastic rosettes. Abnormality in the relationship between the retina and the retinal pigment epithelium is frequent in cases with spontaneously occurring retinal dsyplasia and is consistent with previous observations that the retinal pigment epithelium influences the development of retinal morphology and function. We believe the normal developmental sequence of cell death and disappearance of necrotic cells may have gone awry in retinal dysplasia.

Classification of chromosomal eye syndromes

Human chromosome disease arises from a change in the number or structure of one or more chromosomes. The multiple genes represented in the duplicated or deleted chromosomes are not usually defective and any systemic abnormalities can be attributed to a change in gene dosage. Banding techniques are now commonly used to identify each chromosome and the specific chromosome duplication and deletion and structural rearrangements can now be identified unambiguously.Most ocular abnormalities have occurred in patients with chromosomal defects. Major ocular abnormalities, such as anophthalmia, cyclopia, retinoblastoma, microphthalmia, corneal opacities, coloboma, cataracts, intraocular cartilage, retinal dysplasia and absent optic nerves; and, minor abnormalities, such as ptosis, abnormal eyelid fissures, and Brushfield spots are present in individuals with abnormal chromosomes. The chromosome errors are usually present in all somatic tissues. Consequently, multiple tissue abnormalities would be expected in most patients with chromosome abnormalities. Mental retardation is very common in those patients with abnormalities of autosomes. Therefore, it is unlikely that an isolated single clinical or histopathological ocular abnormality will be the result of a chromosome error. However, if the individual has multiple systemic abnormalities, then a chromosome error can be considered reasonably. Any chromosome disorder can be identified correctly by an appropriate banding chromosome determination on the affected individuals. With the possible exception of the association of 13ql4- and retinoblastoma, there does not appear to be any pathognomonic ocular abnormalities that occur in individuals with chromosome errors.

Retinal anomalies in trisomy 18

The eyes of three patients with trisomy 18, the second most common human autosomal trisomy, were examined histopathologically. In the posterior retina transmission and scanning electron microscopic examinations reveal cytological details characteristic of immature neural retinas. We are able to confirm the report that the posterior retinal pigment epithelium in trisomy 18 has a paucity of mature melanosomes and, in fact, resembles human albino retinal pigment epithelium. The association of hypopigmentation and retinal immaturity suggests pigmentation plays a role in the control of the maturation of the neural retina. Die Augen von drei Patienten mit Trisomie 18, die zweithäufigste menschliche autosome Trisomie, wurden histopathologisch untersucht. Transmission- und rasterelectronmikroskopische Befunde zeigen zytologische Einzelheiten in der hinteren Netzhaut, die für unreife Neuralretina charakteristisch sind. Wir sind in der Lage das Ergebnis zu bestätigen, daß bei der Trisomie 18 das Pigmentepithel der hinteren Netzhaut einen Mangel an reifen Malanosomen aufweist und dem Netzhautpigmentepithel eines menschlichen Albinos ähnelt. Der Zusammenhang zwischen Hypopigmentierung und unreifer Netzhaut legt nahe, daß bei der Kontrolle des Reifungsprozesses der Neuralretina die Pigmentierung eine Rolle spielt.

Premature Cataracts Associated with Generalized Lentigo

Generalized lentigo (leopard syndrome) is an autosomal dominant trait characterized by lentigo, sensorineural deafness, retarded growth (below 25%), ocular hypertelorism, mandibular prognathism, pectus carinatum or excavatum, dorsal kyphosis, winging of the scapulae, valvular pulmonary artery stenosis, electrocardiographic conduction defects, and genitourinary defects. Ocular evaluations of patients with generalized lentigo have revealed the appearance of multiple small white punctate and comma-shaped opacities in the cortex and nuclci of the lenses of affected patients. On the basis of age of the patients examined, it would seem that the corneal opacities first appear in the third decade. Although the opacities may be extensive, the lens opacities do not appear to impair visual function until approximately twenty years after they first appear.