Chondrodysplasia, metaphyseal (McKusick type)

Also known as cartilage hair hypoplasia syndrome, this is a specific genetic form of short-limbed dwarfism with skeletal features that also include normal head, inability to fully extends the elbows, chest cage deformity, bow legs (genu varum), and the tibia shorter than the fibula. The fingers are usually loose-jointed and the fingernails foreshortened. Biopsy shows hypoplasia (underdevelopment) of cartilage to be the nature of the skeletal abnormality. The hair is unusually fine, sparse and light-colored. Microscopically, it has an abnormally small caliber. Many patients with cartilage hair hypoplasia have a major immunologic defect that is manifested, for example, as an unusual susceptibility to chickenpox. In addition to lymphopenia (lack of lymphocytes), some patients have anemia and neutropenia (lack of neutrophiliuc white blood cells). There is an increased malignancy risk, especially lymphoma and skin cancer. A condition called aganglionic megacolon (Hirschsprung disease) is also found in some patients. Cartilage hair hypoplasia was first recognized by Victor McKusick and colleagues in 1965 as a distinct entity in the Old Order Amish, a religious isolate, but was later identified in other groups. In the original study of the Amish, 6 cases of fatal varicella (chickenpox) pneumonia were noted. Inheritance of the syndrome is autosomal recessive. The gene is on chromosome 9 in band 9p13. The child who receives the gene from both parents has the syndrome. Not everyone with the syndrome is dwarfed. Patients may be relatively tall; at least 1 Amish woman with the syndrome is 55 inches tall. There is a remarkable degree of variability in all features of the syndrome. The hair may be seemingly completely unaffected; some patients suffer no apparent immunologic or hematologic defect. Diagnosis of the syndrome in the first year or so of life may be difficult. Perhaps the best known person with the syndrome was Billy Barty (1924-2000), the diminutive actor, who founded Little People of America, an important advocacy group for persons with all forms of dwarfism.