Compiling a national register of babies born with anophthalmia/microphthalmia in England 1988-94. (1/86)

AIM: To describe the prevalence of anophthalmia/microphthalmia in babies born in England 1988-94, as well as their overall survival, and the incidence of associated eye and non-eye malformations; to determine the usefulness of different sources of medical and health service information for establishing a retrospective register of anophthalmia/microphthalmia. METHODS: Multiple sources for initial (retrospective) case ascertainment were surveyed, followed by questionnaires to clinicians to establish severity, associated malformations, and aetiology for England, 1988-94. The population surveyed was all births in England for this time period (4,570,350 births). Cases included live births, stillbirths, or terminations after prenatal diagnosis of congenital anomaly, with anophthalmia/microphthalmia, with or without other malformations and syndromes. Trisomy 13 was subsequently excluded. RESULTS: The proportion of cases notified by any one information source was not more than 26% (Office for National Statistics Register 22%, paediatricians 26%, district sources 25%). Sixty nine per cent of cases (51% of severe cases) were notified by only one source. A total of 449 cases were reported, prevalence 1.0 per 10,000 births. The prevalence was stable over time, although the proportion notified by clinicians rose in more recent years. Thirty four per cent of affected babies had mild microphthalmia. Of those with severe anophthalmia/microphthalmia, 51% were bilateral, other eye malformations were present in 72%, non-eye malformations in 65%, and a "known aetiology" was attributed in 22%. Three quarters of those severely affected survived infancy. CONCLUSIONS: Despite high response rates from the sources of information contacted, the lack of duplication between sources indicates the difficulties of retrospective ascertainment and the need for multiple sources when establishing a register. Anophthalmos/microphthalmos is usually associated with other malformations. Most cases are of unknown aetiology.  (+info)

Anophthalmia in litters of female rats treated with the food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. (2/86)

Anophthalmia in litters of pregnant rats treated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a food-derived carcinogen, was incidentally encountered in a risk-assessment study with 2-generation exposure to PhIP. Female Fischer 344 animals were given 200 ppm PhIP in the diet for 4 wk before mating with nontreated males and also during gestation and lactation periods. Mean numbers of newborn rats per litter in control and PhIP-treated groups were 7.9 +/- 2.9 and 7.1 +/- 1.6 in trial 1 and 8.3 +/- 1.9 and 6.1 +/- 2.4 in trial 2. Among 49 (trial 1) and 63 (trial 2) offspring from PhIP-treated dams, 9 (18.4%) and 32 (50.8%) demonstrated anophthalmia, and 1 (2.0%) and 8 (12.7%) demonstrated hydrocephaly. Five of 7 (71.4%) and 13 of 14 (92.9%) dams delivered pups with malformations in trials 1 and 2, respectively. Also, in a previous study that was carried out with the same protocol and that used the Sprague-Dawley strain of rats, anophthalmia and hydrocephaly were observed in 2 and 1 out of 175 pups, respectively, from 100 ppm PhIP-treated dams. No congenital malformations were found in control groups of the same size in either experiment. In addition to having been previously identified as a cause of carcinogenic activity, our findings suggest that PhIP is capable of causing anophthalmia in rats when administered during the gestational period.  (+info)

Anophthalmia and retinal degeneration associated with stenosis of the optic foramen in Fischer 344 rats. (3/86)

Bilateral anophthalmia was discovered in a male rat (No. 1) and unilateral anophthalmia was found in the left eye of two female rats (Nos. 2 and 3) derived from a Fischer 344 inbred colony. One male rat (No. 4), a littermate of No. 3, had externally normal eyes, but his left eye had severe retinal atrophy, which was detected by ophthalmoscopy. The eyelids in both eyes of No. 1 and in the left eyes of Nos. 2 and 3 were present. Radiography of the skull revealed small optic foramina on both sides of No. 1 and on the affected side of Nos. 2, 3, and 4. Histologically, both globes and optic nerves (ONs) of No. 1 and the left globe and ONs of Nos. 2 and 3 were completely missing. Diffuse retinal degeneration in the left globe and axonal degeneration in the left ON and the right optic tract were observed in No. 4. Dysplasia of the sphenoid bone associated with stenosis of the optic foramen was detected on the affected side of all rats. Thus, ON aplasia in anophthalmic rats and atrophic ON in a rat with retinal degeneration seem to be closely related to stenosis of the optic foramen.  (+info)

Total retinal degeneration in apparent anophthalmos of the Syrian hamster. (4/86)

Anophthalmia in the Syrian hamster was found to result from an extensive degeneration of retinal tissue and tissues derived from the retina. Eyes of affected animals were normal at the twelfth day of gestation (the average gestation period in the Syrian hamster is 16 days). However, the retina of these eyes showed rapid and extensive degeneration during the first two weeks after birth. In adults, the sclera-choroid complex was the only prominent structure of the original eye, with an occasional remnant of deteriorated lens.  (+info)

Spontaneous reversal of nystagmus in the dark. (5/86)

AIM: To report five children with horizontal jerk nystagmus in whom eye movement recordings in the dark revealed a spontaneous reversal in the direction of the nystagmus beat. Three patients were blind in one eye and were diagnosed as having a manifest latent nystagmus (MLN), and two patients had strabismus and congenital nystagmus (CN). METHODS: Eye movements were recorded using DC electro-oculography with simultaneous video recording, including infrared recording in total darkness. RESULTS: Four patients had decelerating velocity slow phase jerk nystagmus when recorded under natural lighting conditions; the fifth case had accelerating velocity and linear slow phase jerk nystagmus. Under absolute darkness, nystagmus reversed in direction of beat with a mixture of linear and decelerating velocity slow phase waveforms. One child with unilateral anophthalmos could wilfully reverse the beat direction of his nystagmus by trying to look with his blind eye in the light and dark. CONCLUSIONS: These observations support the theory that LN/MLN beat direction is determined by the "presumed" viewing eye and may be consciously controlled. The spontaneous reversal of beat direction in the dark suggests eye dominance is predetermined. Eye movement recordings identified mixed nystagmus waveforms indicating that CN (accelerating velocity slow phases) and LN/MLN (linear/decelerating velocity slow phases) coexist in these subjects.  (+info)

National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: investigation of genetic aetiology. (6/86)

We report an epidemiological and genetic study attempting complete ascertainment of subjects with microphthalmia, anophthalmia, and coloboma (MAC) born in Scotland during a 16 year period beginning on 1 January 1981. A total of 198 cases were confirmed giving a minimum live birth prevalence of 19 per 100 000. One hundred and twenty-two MAC cases (61.6%) from 115 different families were clinically examined and detailed pregnancy, medical, and family histories obtained. A simple, rational, and apparently robust classification of the eye phenotype was developed based on the presence or absence of a defect in closure of the optic (choroidal) fissure. A total of 85/122 (69.7%) of cases had optic fissure closure defects (OFCD), 12/122 (9.8%) had non-OFCD, and 25/122 (20.5%) had defects that were unclassifiable owing to the severity of the corneal or anterior chamber abnormality. Segregation analysis assuming single and multiple incomplete ascertainment, respectively, returned a sib recurrence risk of 6% and 10% in the whole group and 8.1% and 13.3% in the OFCD subgroup. Significant recurrence risks were found in both unilateral and bilateral disease. In four families, one parent had an OFCD, two of which were new diagnoses in asymptomatic subjects. All recurrences in first degree relatives occurred in the OFCD group with a single first cousin recurrence seen in the non-OFCD group. A total of 84/122 of the MAC cases were screened for mutations in the coding regions of PAX6, CHX10, and SIX3. No pathogenic mutations were identified in the OFCD cases. A single PAX6 homeodomain missense mutation was identified in a subject with partial aniridia that had been initially misclassified as coloboma.  (+info)

A case of growth hormone and gonadotropin deficiency associated with unilateral anophthalmia, microphallus, cryptorchidism, and mental retardation. (7/86)

We report a rare case of growth hormone and gonadotropin deficiency associated with dysmorphic features. A 16-year-old boy had left anophthalmia, microphallus, bilateral cryptorchidism, and mental retardation. His chromosomal karyotype was normal, 46, XY. Endocrinological studies revealed growth hormone and gonadotropin deficiency, attributed to hypothalamic dysfunction. Magnetic resonance imaging scan of the head showed a hypoplastic pituitary gland, decreased high intensity signals in the pituitary posterior lobe, absence of the left eye, and a hypoplastic left optic nerve with no abnormality of the pituitary stalk, corpus callosum, or septum pellucidum. Although not completely consistent with the features of septo-optic dysplasia (SOD), his condition was considered within the spectrum of SOD. Despite similarities to the Hesx1 knockout mouse, a model of human SOD, mutation analyses revealed no mutations or polymorphisms in coding regions of any exons or intron-exon boundaries of the HESX1 gene. Further genetic studies of this patient may improve understanding of molecular mechanisms involved in pituitary development.  (+info)

Delineation of an estimated 6.7 MB candidate interval for an anophthalmia gene at 3q26.33-q28 and description of the syndrome associated with visible chromosome deletions of this region. (8/86)

Anophthalmia or microphthalmia occur in approximately one in 10 children who have severe visual impairment. These eye malformations are often of unknown aetiology, but can be inherited in autosomal dominant, recessive or X-linked forms, and can also occur in association with specific chromosome abnormalities. Four children are described in the medical literature with microphthalmia or anophthalmia in association with chromosome rearrangements involving distal 3q, suggesting the presence of a micro/anophthalmia gene in this region. We have identified two further patients with micro/anophthalmia and chromosome rearrangements involving 3q26-->3q27 and identified a 6.7 MB common deleted region. Patient 1 had multiple abnormalities including bilateral anophthalmia, abnormalities of the first and second cranial nerves and partial absence of the corpus callosum. His karyotype was 46,XY,del(3)(q26.33q28). Patient 2 had right anophthalmia and left extreme microphthalmia. Her karyotype was 46,XX,del(3)(q26.33q28)t(3;7)(q28;q21.1). Both patients had intrauterine growth retardation (IUGR) and strikingly similar dysmorphic facies consisting of bossed forehead, downward-slanting palpebral fissures, grooved bridge of the nose, prominent low-set ears, small down-turned mouth and small mandible. We identified BAC clones mapping to distal 3q from the ENSEMBL and NCBI Entrez databases. These BAC clones were used as fluorescence in situ hybridisation (FISH) probes to identify the minimum deleted region common to both patients. This interval, between clones RPC11-134F2 and RPC11-132N15, was estimated to be 6.7 MB. We conclude that there is an anophthalmia locus within this interval. Candidate genes mapping to this region include Chordin and DVL3, a homologue of the Drosophila Dishevelled gene.  (+info)

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