Metaphyseal dysplasia

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Metaphyseal dysplasia


Metaphyseal dysplasia is a very rare disorder in which the outer part of the shafts of long bones is unusually thin with a tendency to fracture. Aside from valgus knee deformities (commonly known as knock-knee), many patients with metaphyseal dysplasia exhibit few or no symptoms. However, the disorder comes in a variety of forms, some of which cause serious problems including mental retardation, blindness, and deafness.


Metaphyseal dysplasia is frequently mistaken for craniometaphyseal dysplasia, a disorder characterized by the thickening of the bones of the head. Metaphyseal dysplasia is genetically distinct from craniometaphyseal dysplasia and has only mild effects on the skull. In fact, metaphyseal dysplasia is so subtle, often it cannot be detected by clinical observation and is uncovered only when x rays are taken for another purpose. The signs are immediately visible on x rays, however, particularly the cone-like flaring that occurs on the tubular bones of the leg. This flaring is similar in shape to the Erlenmeyer glass flasks used in laboratories.

Another name for metaphyseal dysplasia is Pyle's disease, after Edwin Pyle (1891-1961), an orthopedic surgeon in Waterbury, CT who first described it in 1931.

There are eight varieties of metaphyseal dysplasia. They are classified as: Jansen type, Schmid type, McKusick type, metaphyseal anadysplasia, Shwachman Diamond metaphyseal dysplasia, adenosine deaminase deficiency, Spahr type metaphyseal chondrodysplasia, and metaphyseal acroscyphodysplasia.

Genetic profile

Inheritance of metaphyseal dysplasia is autosomal recessive, meaning that both parents are carriers of an abnormal gene when a child exhibits symptoms. Children inheriting the gene from one parent become carriers. When both parents are carriers, each child has a 25% chance of having the disorder and a 50% chance of being a carrier. In the case of Jansen-type metaphyseal dysplasia, the chromosomal gene locus is 3p22-p21.1. In Schmid type metaphyseal dysplasia, the locus is 6q21-q22.3. For McKusick type (cartilage-hair hypoplasia), it is 9p13. In adenosine deaminase deficiency, the locus is 20q-13.11. The modes of inheritance for Jansen type, Schmid type, and adenosine deaminase deficiency are all autosomal dominant, meaning that a child may inherit the disorder if just one parent is a carrier. For all other varieties of metaphyseal dysplasia the modes are autosomal recessive, with the possible exception of metaphyseal anadysplasia, which may be X-linked recessive. In that case, whenever one parent is a carrier of the disorder, each child would have a chance of either inheriting it or being a carrier.


This disorder is very rare, and the number of recorded cases is too small to draw firm demographic conclusions. There appears to be no preference based on sex.

Signs and symptoms

The characteristic sign of metaphyseal dysplasia is splaying of the long bones, more severely than in craniometaphyseal dysplasia. Gross Erlenmeyer flask flaring is seen in the tubular bones of the leg, particularly in the femur. Unlike craniometaphyseal dysplasia, few signs occur in the skull in metaphyseal dysplasia, apart from protrusions over the eye sockets.

Metaphyseal dysplasia is also marked by expanded bones of the rib cage and pelvis, and by changes in the angle of the lower jaw. The humerus bone of the arm tends to be unusually broad. Other signs include scoliosis (a sideways curvature of the spine) and osteoporosis (a condition that makes bones brittle). Patients may complain of muscle weakness or joint pain. Dentists may notice malocclusion, an inability of the teeth to properly close. Some spinal changes are possible, associated with the flaring of tubular bones. These may include platyspondyly, a broadening of the vertebrae.

Jansen type

In addition to the above-mentioned signs, Jansen-type metaphyseal chondrodysplasia is characterized by short arms, legs, and stature (short-limbed dwarfism), which become apparent during early childhood. Affected children experience a gradual stiffening and swelling of their joints. Often, they develop a characteristic "waddling gait" and a stance that appears as if they were squatting. Some facial abnormalities may be evident at birth. These include prominent, widely spaced eyes, a receding chin, or a highly arched palate. Some affected adults develop unusually hardened bones in the back of the head, which sometimes results in deafness and/or blindness. Abnormal cartilage development may harden into rounded bone masses that may be noticeable on the hands, feet, and elsewhere. Other signs and symptoms associated with Jansen-type metaphyseal chondrodysplasia include clubbed fingers, a fifth finger permanently fixed in a bent position, fractured ribs, mental retardation, psychomotor retardation, and high blood levels of calcium. Curvature of the spine in these patients may be front-to-back as well as sideways. Testing the blood and urine for calcium can assist in confirming a diagnosis. Jansen-type metaphyseal chondrodysplasia was formerly referred to as metaphyseal dysostosis.

Schmid type

Like Jansen-type metaphyseal chondrodysplasia, Schmid type metaphyseal chondrodysplasia is also characterized by short-limbed dwarfism. Other special features may include an outward "flaring" of the lower rib cage, bowed legs, leg pain, a normal spine, and a hip deformity that causes the thigh bone to angle toward the body's center. Schmid type metaphyseal chondrodysplasia was first discovered in 1943 in a family of Mormons that had experienced 40 cases of the disorder over four generations. The first affected ancestor was traced back to 1833.

McKusick type

Like Jansen type and Schmid type, McKusick type metaphyseal chondrodysplasia is marked by short-limb dwarfism. Other features include thin, light-colored hair, loose-jointed fingers, elbows that cannot be fully extended, Hirschsprung disease (a birth defect in which the usual nerve network fails to develop around the rectum, and in some cases, the colon), and abnormalities of the immune system. In the shin, the tibia bone is uncharacteristically shorter than the fibula. Patients are at increased risk of developing cancers, especially of the skin and the lymph nodes. McKusick type metaphyseal chondrodysplasia is also known as cartilage hair hypoplasia syndrome. The disorder was first recognized in 1965 among the Old Order Amish. Billy Barty (1924-2000), the actor who founded the dwarfism advocacy group Little People of America, had McKusick type metaphyseal chondrodysplasia.

Metaphyseal anadysplasia

First noticed in 1971, metaphyseal anadysplasia is a form of metaphyseal dysplasia that starts early. Instead of appearing after puberty, some signs were found to be present at birth, but disappeared after two years. For example, parts of the long bones were irregular. In the thigh bones of these patients, there was an unusually low level of red blood cell production.

Shwachman-Diamond syndrome

In addition to the skeletal system, Shwachman-Diamond syndrome also affects the pancreas. It is characterized by inadequate absorption of fats because of abnormal pancreatic development and bone marrow dysfunction. Other unusual symptoms and signs include short stature, liver abnormalities, and low levels of any or all blood cells. Reduced levels of white blood cells may cause these patients to be vulnerable to repeated bouts with pneumonia, otitis media, and other bacterial infections. Shwachman-Diamond syndrome is also referred to as Shwachman-Bodian syndrome, Shwachman-Diamond-Oski syndrome, Shwachman syndrome, and congenital lipomatosis of the pancreas. Some researchers call it pancreatic insufficiency and bone marrow dysfunction.

Adenosine deaminase deficiency

A deficiency of Adenosine deaminase (ADA), an essential, broadly distributed enzyme, causes severe combined immunodeficiency disease. This can bring about a wide range of effects, including asthma , pneumonia, sinusitis, diarrhea, problems with the liver, kidneys, spleen and skeletal system, and failure to thrive. ADA deficiency is similar to McKusick type metaphyseal chondrodysplasia in that both disorders include skeletal changes and problems with cellular immunity. ADA deficiency earned a special place in genetics history in 1990, when, in the first application of gene therapy in humans, it was corrected using genetically engineered blood.

Spahr type metaphyseal chondrodysplasia

This is one of several disorders that used to be called metaphyseal dysostosis. It is extremely rare, and its features include severely bowed legs and short-statured dwarfism. In some cases, the bowing of the knees is so severe as to require surgical correction. Spahr type is very similar to Schmid type metaphyseal chondrodysplasia, except that inheritance is believed to be autosomal recessive in Spahr type, unlike Schmid type, which is autosomal dominant.

Metaphyseal acroscyphodysplasia

This variety is also referred to as wedge-shaped epiphyses of the knees. Its special features include severely retarded growth, psychomotor retardation, abnormally small arms and legs, extremely short fingers, and curvature of the knees.


Diagnosis is usually by x ray, in which the bone deformities of metaphyseal dysplasia are very noticeable, even if not apparent in a normal clinical examination. A medical doctor will look for valgus knee deformities. A radiologist will look for Erlenmeyer-flask shaped femur bones and ensure that any deformities to cranial bones are minor, to rule out craniometaphyseal dysplasia. The radiologist will also watch for abnormally broad humerus, radius, and ulna bones.

Treatment and management

Metaphyseal dysplasia cannot be directly treated, but some individual symptoms, such as osteoporosis or joint problems, may be treated or surgically corrected.


In many cases, patients with metaphyseal dysplasia may be symptomless and very healthy. Other patients, including those with Jansen-type metaphyseal chondrodysplasia, may have more severe complications including blindness, deafness, or mental retardation.



Pyle, E. "Case of unusual bone development." Journal of Bone and Joint Surgery (1931): 3: 874-876.

Raad, M. S., and P. Beighton. "Autosomal recessive inheritance of metaphyseal dysplasia (Pyle disease)." Clinical Genetics (1978) 14: 251-256.

Turra. S., C. Gigante, G. Pavanini, C. Bardi. "Spinal involvement in Pyle's disease." Pediatric Radiology (January 2000) 25-27.

David L. Helwig