Medicine: Inbreeding & Dwarfism

For geneticists the fascinating fact about the Old Order Amish, one of the sects of the Pennsylvania Dutch country’s “Plain People,” is that they all are descended from about 200 immigrants of 200 years ago. A few Amish leave the ancestral acres and simple (no motors, no worldly entertainments) way of life, but virtually no new blood has been introduced to create genetic confusion. For such a group, to survive is to inbreed, and the Amish have more than survived; they now number 44,000. In 1963, to take advantage of this unique opportunity into the land of the black buggy, the beard and the modest bonnet went Johns Hopkins’ Dr. Victor A. McKusick, an epidemiologist as well as a geneticist. And last week at Bar Harbor out came a detailed report on two forms of dwarfism, one recognized only a generation ago, the other brand-new to medical science.

Samuel’s Seed. The first form is confined, so far as the U.S. is concerned, to the region of Pennsylvania’s Lancaster County around a town called Intercourse. Named the “Ellis-van Creveld Syndrome” after the Scottish and Dutch pediatricians who first reported it in 1940, it has no common name and is so uncommon elsewhere in the world that only about 50 cases had been reported until McKusick’s Hopkins team moved into Pennsylvania. There they found proof of at least 49 cases since 1860, with 24 still living. Most exciting, genetically at least: the Amish keep such exact genealogical records that McKusick was able to trace all 60 parents to whom the 49 were born. And all were descended from a single immigrant and his wife.

It was in 1744 that Samuel King arrived in the U.S. He or his wife (it is impossible now to tell which) had one chromosome marred by a defective gene. Since the gene is a recessive, none of their children showed any sign of its curse, nor did their children’s children. If they had married normally into the U.S. population at large, probably the gene would have stayed quiescent, with only an infinitesimal chance of sad results. But within a couple of generations, King’s descendants began to marry second or third cousins. Eventually, it had to happen: a man who carried the gene married a cousin, of some degree or remove, who also carried it. Their unfortunate offspring inherited a double dose of the bad gene.

Snipped Fingers. The first known case, said Dr. McKusick at Bar Harbor, was born in 1860. Though the Amish average a couple of inches shorter than the general U.S. population, there is no mistaking the deformity. Ellis-van “Creveld dwarfs range in height from only 40 to 60 inches. They have six fingers on each hand, the extra one being on the outside of the hand beyond the little finger. Sometimes (but not consistently) there is a sixth toe on one foot or both. Although it is not conspicuous at birth, many dwarf babies have an abnormal heart with only three chambers instead of four (no septum between the auricles), and a weakness or deficiency of cartilage in the chest and around the windpipe. One-fourth of the dwarf children die of such defects within two weeks of birth. Another fourth of the dwarf babies have less severe heart defects, and survive. Half of them appear to have no heart defects and may achieve a near-normal life span. One such man is now 58. He is one of eight living adult dwarfs (20 or over), and there are 16 children and teenagers.

Most parents have the children’s extra fingers amputated when they are a few months old. The children show no mental retardation or IQ loss. And they probably fare better in the closed Amish community than in the less tolerant world .outside.

Fine Hair. Equally bizarre, and also transmitted through a recessive gene, is the new form of dwarfism found by Dr. McKusick among the Amish in more than a dozen communities. It is a new kind of genetic defect. Doctors who earlier noticed cases of this kind of dwarfism among the Amish mistook it for achondroplasia, a form made familiar by Velásquez’s paintings of dwarfs as court jesters, with short arms and legs, a large head and a “scooped-out” nose. But Dr. McKusick’s team found significant differences. These Amish dwarfs do not have big heads or misshapen noses. Aside from their short arms and legs (from a defect in their cartilage), their only other physical abnormality is their hair. It is light-colored, even in a dark-haired family. It is sparse and very fine (i.e., small diameter). It is brittle and never grows long enough for an Amish mother to braid a dwarf daughter’s locks. Since the main features of this form of dwarfism are underdevelopment of cartilage and hair, Dr. McKusick has named it “cartilage-hair hypoplasia,” or CHH. Only two similar cases have now been found among non-Amish in France and two more in Minnesota.

Certainly, the prevalence of these bad genes has had little effect on fertility: five CHH dwarf men have married normal women and have had normal children. But one CHH dwarf married a CHH woman, and she has borne three CHH dwarf children.