Background The Old Order Amish in Milverton, Ontario, represent a genetically isolated group which originated with 12 founding families in 1824. Due to inbreeding and founder effect, certain genetic disorders have become highly prevalent in Ontario Amish.

Objective This study aims to describe the spectrum of genetic disorders observed in the Old Order Amish of Southwestern Ontario (population size ˜ 2500).

Design and method Over the past 25 years, we have documented the clinical phenotype, and molecular aetiology of genetic disorders in Old Order Amish children.

Results A disorder characterised by acute encephalopathy with fever, visual hallucinations, hearing loss, and retinal dystrophy was observed in 7 out of about 220 families, caused by mutation in the histidyl t-RNA synthetase (HARS) gene. Acute respiratory distress syndrome may lead to sudden death. This disorder was first reported in the Amish in Pennsylvania. Other disorders observed in the Ontario Amish but not in American Amish include endocrine-osteodysplasia syndrome (ICK), cerebral atrophy (TMPRSS4), cystinosis (CTNS), sodium diarrhoea (SPINT2), juvenile-onset glaucoma (CYP1B1), epidermolysis bullosa simplex, and Fraser syndrome (FRAS1). Lethal disorders include a central hypoventilation syndrome, a disorder with oligohydramnios and renal hypoplasia, and ichthyosis-microcephaly. In total, the causative mutations have been found for 8 disorders, while another 5 disorders are presumed autosomal recessive.  Knowledge of these disorders enabled molecular diagnosis of a child affected concurrently with two conditions within 5 days of birth.

Conclusion Awareness of genetic disorders common in this population will aid in early diagnosis and management, and avoid the diagnostic odyssey.