Increasing incidence of optic nerve hypoplasia/septo-optic dysplasia spectrum: Geographic clustering in Northern Canada

Abstract

Introduction: Owing to the shared embryonic origin, defects in development of optic nerves are often seen in conjunction with defects affecting the surrounding brain and pituitary gland. Optic nerve hypoplasia (ONH) and septo-optic dysplasia (SOD) represent a clinical spectrum associated with visual, pituitary and severe central nervous system structural abnormalities (SODplus). Based on changing clinical patterns, our primary objective was to examine trends in annual incidence of ONH/SOD and geographical clustering in Manitoba.

Methods: This was a retrospective 1996 to 2015 chart review with extraction of anthropometric measures, radiologic findings, parental characteristics, endocrinopathies and neurologic symptoms from all involved in care. Postal codes were used to assign map co-ordinates and identify relevant census-based deprivation indices.

Results: Ninety-three children were identified in our catchment area; Poisson regression confirmed a striking 1.11-fold annual increase (95% confidence interval 1.07 to 1.16) or ~800% over two decades. The annual incidence (averaged 2010 to 2014 chart data) reached 53.3 per 100,000, affecting 1 in 1875 live births. Most (~55%) had SODplus. Common presenting features were hypoglycemia, nystagmus, seizures and developmental delay; 40% had hormone deficiencies; 80% had reduced visual acuity, typically bilateral. Many were premature with young, primiparous mothers. Unhealthy maternal lifestyles and severe material deprivation were noted. There was disproportionate clustering in individuals from Northern Manitoba at three times the average provincial rate.

Conclusion: We noted a dramatic rise in the annual incidence of ONH/SOD, which was strongly associated with poverty and northern communities. The pattern was consistent with environmental or nutritional etiologies. Many children were severely affected with increased morbidity and health care burdens.

Keywords: Blindness; Hypopituitarism; Incidence; Poverty; Septo-optic dysplasia.

Figure 1.

(a) Normal optic nerve (arrow) and pituitary (short arrow), normal corpus callosum (line). (b) Thin optic nerve (arrow) and very small anterior pituitary (short arrow), ectopic posterior pituitary (horizontal arrow) and thin corpus callosum. (c) Closed lip schizencephaly (arrow) often found in SODplus. (d) Incidence of ONH/SOD from 1995 to June 2015 (n=93).

Figure 2.

Incidence per 100,000 youth <19y by Federal Electoral District (FED). P < 0.001 by Fiser Exact test (dotted line = average for all Manitoba districts). 1 Kenora; 2 Thunder Bay & Rainy River, ON; 3 Brandon-Souris; 4 Charleswood; 5 Churchill; 6 Dauphin; 7 Elmwood; 8 Kildonan; 9 Portage; 10 Provencher; 11 Saint Boniface; 12 Selkirk; 13 Winnipeg Centre; 14 Winnipeg North; 15 Winnipeg South; 16 Winnipeg South Centre; 17 Nunavut.

Figure 3.

Distribution of ONH/SOD/SODplus in Manitoba, West Nunamvut or North West Ontario. Dark boundaries represent Federal Electoral Districts (FEDs) with comparable populations of 80-100k (except for Nunavut at 31k). Annotations represent the number of children with ONH/SOD in each. Individual points have been jittered to improve visibility, but each dot in the urban Winnipeg area represents multiple cases.