Linkage studies of Best's macular dystrophy.

Genetic linkage studies are presented for nine kindreds with Best's vitelliform macular dystrophy (BVMD). This condition is an autosomal dominant macular dystrophy with reduced penetrance and highly variable expressivity. Asymptomatic carriers were identified with electro-oculography, fundus photographs and fluorescein angiography. Blood and saliva specimens were obtained from informative family members and genotyped for 26 polymorphic genetic traits. No firm evidence was found for linkage between BVMD and 18 informative markers; the highest positive lod score was z = 0.57 for GPT1 at a recombination fraction of theta = 0.30. An atypical form of vitelliform macular dystrophy (VMD-1) is linked to GPT1 (theta less than 0.05) and is provisionally assigned to chromosome 16pter-p11. Our data are not sufficient to rule out loose linkage for GPT1 and BVMD. Thus we were not able to determine whether BVMD and VMD-1 are allelic mutations or separate genetic disorders. Additional linkage and gene mapping studies of these loci and BVMD (as well as other atypical forms of macular dystrophy) would be useful to further delineate these disorders.

Cell proliferation in response to vitreous hemoglobin.

Rabbits were examined at intervals to 90 days after receiving two or three intravitreal injections, on consecutive days, of homologous hemoglobin or saline. Cell proliferation in the vitreous was assessed by scintillation counting and radioautography after intravitreal administration of 3H-thymidine 4 hr prior to sacrifice. Two populations of vitreous cells phagocytize the vitreous hemoglobin and are stimulated to DNA synthesis. Cells that migrate into the vitreous in response to hemoglobin also contribute to total 3H-thymidine uptake. Tritiated thymidine incorporation peaks between 5 to 10 days and again between 22 to 30 days after the first administration of hemoglobin. By 45 to 60 days after two injections and 90 days after three injections the vitreous cell proliferative activity has returned to normal. It is concluded that a bleeding event which leads to the release of hemoglobin in the vitreous stimulates a minor, transient vitreous cell proliferation and a more significant, but also transient, migration of cells into the vitreous. Aside from contributing by phagocytosis to vitreal clearing, no other functions have been ascribed to these cells.

Ectopia lentis et pupillae.

Two brothers whose parents were second cousins had ectopia lentis et pupillae. This autosomal recessive disorder is distinguished from other disorders with ectopia lentis by the limitation of abnormalities to the bilateral displacement of lens and pupil.

Abnormal iris vasculature in myotonic dystrophy. An anterior segment angiographic study.

The microvasculature of the iris was studied in 35 patients with neuromuscular disease and 14 control subjects, using anterior segment fluorescein angiography. Myotonic muscular dystrophy, in which a variety of ocular changes have previously been reported, was found to be associated with both focal and generalized vascular abnormalities. Changes were seen in the fluorescein angiograms of all nine of the myotonic dystrophy patients in which the iris vessels could be seen. No evidence of a microcirculatory disorder was seen in patients with Duchenne's dystrophy, for which a vascular pathogenesis has been proposed. The angiograms of patients with limb-girdle dystrophy, facioscapulohumeral dystrophy, and Friedreich's ataxia were also normal.

The Rieger syndrome.

Fourteen patients with hypodontia and the ocular features of the Rieger syndrome were examined for the presence of systemic anomalies. A periumbilical defect that consisted of failure of the periumbilical skin to involute was seen in ten of the thirteen evaluated for the defect. Three others had scars over the umbilical area and had a history of surgery for herniation. In addition, four males in one family and one male from another family had hypospadias. None of several other anomalies reported to be components of the Rieger syndrome by other authors was detected in the fourteen patients. The mode of inheritance in the familial cases studied was compatible with autosomal dominance. The results of this study indicate that the Rieger syndrome is an autosomal dominant syndrome whose cardinal features are hypodontia, goniodysgenesis, and failure of the periumbilical skin to involute properly.

Retinoblastoma in a patient with a 13qXp translocation.

An infant girl with failure to thrive and bilateral retinoblastoma had a translocation of the long arm of chromosome 13 to the short arm of the X chromosome, and possible loss of a portion of the q 14 band. The lack of other major organ malformations in this patient emphasized the importance of considering chromosomal aberrations as a possible etiology of retinoblastoma in patients with nonspecific psychomotor retardation.

A clinical and histopathological study of François-Neetens speckled corneal dystrophy.

A 57-year-old black man had François-Neetens speckled dystrophy of the cornea and orbital phycomycosis. Examination of family members confirmed an auto-somal-dominant pattern of inheritance. Light and electron microscopic study of the cornea of a blind eye disclosed that the corneal opacities were represented by swollen, vacuolated keratocytes filled with histochemically demonstrable acid mucopolysaccharide and complex lipids. Thus, this dystrophy may represent a dominantly inherited metabolic disorder confined to the cornea.

Familial nanophthalmos.

Four members of one sibship had microphthalmos with fundi having an irregular "rippled* appearance with alternating light and dark red coloration. Fluorescein angiography revealed patchy choriocapillaris perfusion with unusually rapid diffusion into the retina. Genealogic and geographic data strongly suggest autosomal-recessive inheritance. Only one patient developed glaucoma. The unique combination of abnormalities in this family suggests that a new recessive mutation may be responsible.

Differential diagnosis and treatment of dislocated lenses.

Ectopia lentis continues to be a perplexing diagnostic and therapeutic problem for most ophthalmologists. However, thorough investigation, both systemic and ocular, can in most cases, establish either an environmental etiology or the nature of the heritable disorder. In cases with systemic disease and ectopia lentis, the ophthalmologist should insure that each patient obtains adequate consultation with other specialists in order that proper prophylactic and therapeutic measures are available. The Marfan syndrome, homocystinuria, and the Weill-Marchesani together account for the majority of dislocated lenses. Each of these requires a somewhat different therapeutic approach. Glaucoma should be recognized as a frequent complication in each of these conditions but is most serious in the Weill-Marchesani syndrome in which it often occurs early in life and remains unrecognized until serious damage has occurred. Because of the pupillary-block nature of the glaucoma in this condition, a prophylactic peripheral iridectomy must be seriously considered in every case while lens surgery should be undertaken if the glaucoma cannot be controlled by medical or surgical means. In homocystinuria, because of the potential vascular complications of general anesthesia, the ophthalmologist is often in a dilemma. The lens in this condition seems to be more mobile than in other ectopia lentis disorders and therefore likely to compromise vision earlier in life. However, due to the risk of vascular thrombosis, lens surgery should be delayed whenever possible until the patient is old enough to tolerate local anesthesia. Likewise, patients with the Marfan syndrome should be handled conservatively and, in general, function quite well simple with spectacle correction. Due to the high frequency of immediate surgical complications, it is advisable to avoid an open-sky technique to lens removal, using aspiration or a pars plana approach instead.

Genetic counseling of families with Best macular dystrophy.

We have examined 233 members of eight families with BMD. Of these, 169 were also examined with EOG. Sibships wherer greater than or equal to 80% of members were examined clinically and with EOG totaled 39. The results established both the validity and reliability of EOG testing in detecting people genetically affected with BMD. Hyperopia is established as an important manifestation of the disease. The visual prognosis of BMD is described.