Hereditary Multiple Exostoses

A CASE of multiple exostoses instance of multiple of a family 1845. The hereditary origin of certain cases of multiple exostoses was first clearly recognized in 1890, by which time about 40 families had been described as exhibiting two or more members. In all hereditary cases subsequently described it appears that exostoses have been associated with enchondromata either in the same family or other members of the family. Concerning their mode of inheritance, the two disorders are closely related. The outgrowths from the perichondrium are not always multiple and some members may have an isolated growth. Unnoticed small outgrowths, slight deformities or confusion with rickets may obscure the heredity factor. The trait has been observed to miss a generation and pass on to the next generation through an unaffected female. A group of 765 cases with definite familial history occurring in 183 families has been assembled (1).

A CASE of multiple exostoses was first reported in 1837 and the first instance of multiple exostoses observed in several members of a family was in 1845. The hereditary origin of certain cases of multiple exostoses was first clearly recognized in 1890, by which time about 40 families had been described as exhibiting two or more members. In all hereditary cases subsequently described it appears that exostoses have been associated with enchondromata either in the same family or other members of the family. Concerning their mode of inheritance, the two disorders are closely related. The outgrowths from the perichondrium are not always multiple and some members may have an isolated growth. Unnoticed small outgrowths, slight deformities or confusion with rickets may obscure the heredity factor. The trait has been observed to miss a generation and pass on to the next generation through an unaffected female. A group of 765 cases with definite familial history occurring in 183 families has been assembled (1).
It has been observed to occur in 716 males (69%) and 312 females of a group of 1028 cases. It is interesting that the sex ratio in the non-hereditary type is the same as the hereditary type (1).
The age of onset of the hereditary type is usually from birth through the growth period. The abnormality is found from birth in 17 per cent of the hereditary type, and in the non-hereditary type only 4.5 per cent have the abnormality at birth (1). The earliest, most common sites of the lesion involve the lower end of the femur and the upper part of the tibia. This is probably due to early appearance of the centers of ossification of these bones.
The number of outgrowths varies greatly. They may appear singly; as many as 1000 have been observed on one patient. The distribution is usually symmetrical. In most cases the patient is short in stature and the deformity is most marked in the forearm, with a bowing of the ulna and radius resulting from the union of these bones during the growing period. It has been observed that some patients have hyperextensibility of the joints. This finding is observed in Family 1 in this study.
It is thought the exostoses which are developing and will involve neighboring bones should be removed. During the growth period the uniting of the bones at their ends will result in bowing. In families where the trait is known to be present, care should be taken to remove the exostoses before deformity results.

Family 1
The mother of the present patient ( Fig. 1 No. 2) died at the age of 23 years. She was short in stature and had deformity of the extremities from the multiple exostoses. The patient's sister has had no indications of the lesions being present, nor have any of her children. The patient's father and children by a second marriage are also free of the symptoms.
The patient ( Fig. 1 No. 3) was a forty-one year old, white male accountant who entered with the chief complaint of multiple bony masses in the area of the left scapula. He had had no accidents.
The present complaint dates back to early childhood when the outgrowths of bone were first noted. They had decreased the rate of growth since the age of puberty. They had caused no pain until the past few weeks when the patient noted pain in the area of the left scapula. He had noted no limitation of motion, but had noted deformity in the extremities. Since early childhood he had noted hyperextensibility of the joints of the hands and feet.
Physical examination showed a thin, short male, 652 inches tall, weighing 109 pounds. Deformities of the extremities were marked. Except for the bony outgrowths the patient was normal on physical examination. Two exostoses were removed from the costal surface of the left scapula. The larger measured 7 x 7 x 6 cm. in size; the other measured 6 .2 x 5 x 4 cm. They both presented a bony pedicle by which they had been attached to IFIG. 4 (left) ami 5 (rioht') Rad(iograp)hs ofexostoses of individual 6, Family 1 42t their parent tissue. These measured 4 cm. in diameter for the larger and 1' 2 cm. for the smaller. The surface was lobulated in appearance and made up of cartilage whereas the central portion was dense bone. Sections taken of the exostoses portion of the masses presented well defined hyaline cartilage. The structure was well formed and there was no evidence of malignancy.
The pathological diagnosis was osteochondromata. The clinical diagnoses were hereditary multiple exostoses and hyperextensibility of the joints of the hands and feet.
His first child ( Fig. 1 No. 5) died by drowning at 22 years. This child was free of the lesions, according to the parents.
The second child ( Fig. 1 No. 6) was a six year old girl whose chief complaint was hay-fever, asthma and allergy to certain fruits. The patient and parents had noted only one bony outgrowth at the left sterno-clavicular joint. She had had hyperextensibility of the joints in the hands and feet since birth.
Her father and paternal grandmother had multiple exostoses. Her mother and brother had hay-fever, asthma and allergy to certain fruits.
Physical examination showed a thin white girl 471 2 inches in height and weighing 41/12 pounds. One bony outgrowth was palpable at the left sternoclavicular joint and one at each of the distal ends of the right and especially the left femur. The serological test for syphilis was negative. The blood count and urinalysis were normal.
X-ray examination of the head and neck revealed no exostoses. The x-ray of the thorax revealed exostoses on the left and right scapula, left clavical at the sterno-clavicular joint, the left humerus at the proximal portion and also a small one on the shaft (Fig. 6). X-ray of the hips and femurs revealed an irregular ilium bilaterally. The femur on the right in the area of the trochanter showed a beginning exostoses. The distal portion of the right and especially the left femur presented osteochondromata. The proximal portions of the right fibula and the distal portion of the right tibia and fibula were involved, (Fig. 6). The distal portion of the left radius presented an exostoses (Fig. 5).
The clinical diagnoses were hereditary multiple exostoses, hay fever and hyperextensibility of the joints of the hands and feet.
The third child was a four year old boy ( Fig. 1 No. 6) with no complaints. His father and sister have multiple exostoses and hyperextensibility of the joints of the hands and feet. His mother has hay-fever, asthma and allergy to certain foods. The patient has had hay-fever, hives, eczema and asthma. No abnormal findings were noted in the patient except for marked hyperextension of the fingers and toes.
The blood count and urinalysis were normal. The serological test for syphilis was negative. X-ray examination revealed no bony abnormality. The clinical diagnosis was hyperextensibility of the joints of the hands and feet.

Family 2
The original patient was the fourth child in the fourth generation. She was a twenty-three year old white female salesclerk (Fig. 6 Generation IV, No. 4).
Her father and paternal grandmother had multiple exostoses, also the grandmother's father had the abnormality. The grandmother was the second wife. The progeny of the first wife, consisting of nine children, were all normal.
The patient first noted a lesion on the right arm at five years of age. She had broken her arm previously and thought the first lesion was related to the healing process. She stated that she thought the lesions were only noted after injury.
About two years before examination the patient fell while skating and injured her back. One year before examination, she noted the onset of weakness of the legs associated with increasing numbness and tingling. There was a definite decrease in the motor power of the legs. Temperature discrimination and position sense were diminished. There was a loss of pain sensation below the third lumbar vertebra. The deep reflexes were hyperactive, with a sustained ankle clonus and bilateral positive Babinski reflexes.
The blood examination and urinalysis were negative. Physical examination was negative except for the deformity present.
X-ray examination of the pelvis, with special reference to the ribs and shoulder girdle, the right femur, both upper extremities, and both hands show an extensive involvement of virtually the entire skeleton with multiple bone exostoses, of both major types, spicule and cauliflower. Fig. 7 and 8.
The right ulna is rather markedly bowed, with dislocation and deformity of I FIG. 6. Familial multiple exostoses, Family 2 the right radial head. An interesting variation is present inl the hands; the third, fourth and fifth metacarpal bones are unusually short. A spinogram demonstrated a complete block to the flow of oil opposite the tenth dorsal vertebra, with some deformity on the right side opposite the eleventh and twelfth dorsal vertebra. Later a laminectomy was done with a good result. The lesion was established to be a large osteochondroma.
Due to osteochondromatous deformity of the pelvis a cesarian section was necessary in a later pregnancy.
The diagnosis was multiple bony exostoses involving the entire skeleton visualized, of both the spicule and cauliflower type, with other bony anomalies of development.
A summary of the third and fourth generations gives some indication of how the hereditary trait is carried. In these two generations there were two unaffected males, and eight unaffected females, making a total of ten unaffected members. There were six affected males and three affected females, making a total of nine positive members. There was one unaffected female carrier who had no exostoses; however, her one son had multiple exostoses. This type of female carrier may account for the many negative females. The ratio of affected to normal inl complete sibships is approximately one to one, suggesting the action of an autosomal dominant gene, probably with reduced penetrance.
This family, as in all other families so involved, shows marked variation in the severity of the abnormality. 2. Four new cases are presented, along with their x-ray findings. 3. The inheritance follows the pattern of a dominant characteristic, with incomplete penetrance in the female.
4. The outgrowths involve neighboring bones early, therefore it is thought advisable to remove the exostoses that are developing to involve other bones and thus perhaps prevent the abnormality. This type of abnormality is often seen in the radius and ulna. 5. Where the family history of the disease is present early examination and treatment are advisable.