Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis

ObjectiveTo evaluate the ophthalmic phenotypes associated with T-cell immune regulator 1 (TCIRG1) mutations in Chinese patients with infantile malignant osteopetrosis (IMO).Methods and analysis27 Chinese TCIRG1-related osteoporosis infants were enrolled using direct DNA sequencing of PCR-amplified exons. 12 cases had frameshift mutation (the frameshift mutation group, group F), and 15 cases had point mutation (the point mutation group, group P). The clinical features of the two groups were compared, including age at onset, gaze qualities, optic atrophy, optic canal stenosis and waveforms of Flash visual-evoked potential (FVEP).ResultsThe clinical signs, except age at onset and FVEP, showed statistically significant differences between the two groups. The mean age at onset was 1.8 months in group F and 4.3 months in group P; 22 eyes (92%) with frameshift mutation and 16 (53%) with point mutation had poor gaze qualities, such as nystagmus and/or strabismus; optic atrophy was found in 16 eyes (67%) in group F and 6 (20%) in group P; the average optic canal diameter was 1.45 mm in the frameshift mutation cases, 1.87 mm in other cases; FVEP indicated that the waveforms in 10 eyes (42%) were not elicited in group F, yet five eyes (17%) in group P.ConclusionIn Chinese TCIRG1-related patients of IMO, the optic canal stenosis and optic atrophy were more serious in cases with frameshift mutations. However, no differences in the conduction block of optic nerve were found between the two groups.

Entrapment neuropathy of the optic nerve due to hyperostosis associated with congenital anemia

✓ The authors report on the case of a 14-year-old boy who presented with bilateral visual impairment due to optic canal stenosis caused by hyperplasia of the bone marrow arising from anemia. The patient had hereditary hemolytic anemia with unstable hemoglobin of the Christchurch type. This congenital form of anemia caused hyperplasia of the bone marrow as well as hyperostosis of the entire calvarial bone, which in turn led to optic canal stenosis. The patient underwent surgical decompression of the optic canal, resulting in significant improvement in visual acuity. Pathological findings in the calvarial bone indicated hypertrophic bone marrow with no other specific features such as neoplastic pattern or fibrous dysplasia. With the exception of objective hearing impairment, no other significant cranial neuropathy has been detected thus far. On reviewing the published literature, this case was found to be the first in which hyperostosis due to congenital anemia resulted in symptomatic entrapment neuropathy of the optic nerve. The authors concluded that surgical decompression effectively improves visual acuity.