A new genetic syndrome among the Old Order Amish of Smicksburg Pennsylvania

Abstract

The Old Order Amish are a religious sect well known for their simple way of life and are of interest to geneticists due to the unique opportunity they provide for the study of genetic diseases. The Old Order Amish have a high rate of consanguinity and therefore have a higher proportion of recessive genetic conditions than non-Amish populations. We have evaluated individuals described as having developmental delays from an Old Order Amish community located in Smicksburg, PA. Approximately 22% of couples in this community are known to be consanguineous. We evaluated one family in which four of the fourteen siblings (two males and two females) had what appeared to be a syndrome previously undescribed among Amish or non-Amish populations. Features seen in all of the siblings included moderate to severe mental retardation, hypotonia, microcephaly, a short philtrum, hypoplastic alae nasi, and a long columella. Three of the siblings had short stature, deep set eyes, prominent lips, pectus excavatum, and hyperextensible joints. Two of the siblings had prominent eyebrows, knee contractures, atrophy of the interossei muscles, disconjugate gaze and hyperreflexia. Other less common findings included delayed sexual maturation, subluxable patellae and cataracts. The individual with cataracts had an ulcerativc ocular illness at age 13 years with subsequent cataract formation. Chromosome analysis, and metabolic testing including urine organic and amino acids were completed and were normal. The parents denied consanguinity Two maternal aunts and an uncle are said to be similarly affected, however they have not consented to an evaluation. Two maternal cousins, brothers to each other and both evaluated by us, also have some overlapping but nonspecific features. The family would not permit photographs at the time of the evaluation.