Pediat. Radiol. 7,215-219 (1978)
Two Peculiar Types of Enchondromatosis* J. Spranger 1, H. K e m p e r d i e c k 2 , H. Bakowski 3, and J. M. Opitz4 1Department of Pediatrics, University of Mainz, FRG; 2Department of Pediatrics, University of DiJsseldorf, FRG; SChildren's Hospital, Plettenberg, FRG; and 4Wisconsin Clinical Genetics Center of the Department of Medical Genetics and the Department of Pediatrics, University of Wisconsin Center for Health Sciences and Medical School, Madison, Wisconsin, USA
Abstract. O n the basis o f 3 p e r s o n a l observations a n d o f 6 cases f r o m the literature, two peculiar types o f e n c h o n d r o m a t o s i s are delineated: 1. Enc h o n d r o m a t o s i s with generalized, irregular vertebral lesions, and 2. G e n e r a l i z e d e n c h o n d r o m a t o s i s with mild platyspondyly. Key words: B o n e dysplasia - E n c h o n d r o m a t o s i s D y s c h o n d r o p l a s i a - O l l i e r disease
Enchondromatosis (Dyschondroplasia, Ollier disease) is characterized by multiple e n c h o n d r o mata originating in the m e t a p h y s e a l regions o f the tubular b o n e s and in fiat bones. T h e lesions are usually bilateral, b u t characteristically a s y m m e t r i c , u n e v e n l y distributed, a n d in various stages o f d e v e l o p m e n t . As a rule, the c u b o i d b o n e s , calvaria and vertebral bodies are spared. R o e n t g e n o g r a m s s h o w multiple, r o u g h l y oval r a d i o l u c e n t defects, f r e q u e n t l y with e x p a n s i o n and cortical t h i n n i n g o f the affected area [5, 7, 9]. T h e r a d i o l u c e n t t u m e factions f r e q u e n t l y contain strands o f b o n e and calcific inclusions creating a cystic a n d / o r b u b b l y appearance. E n c h o n d r o m a t a are also c o m p o n e n t s o f o t h e r disorders s u c h as Maffucci S y n d r o m e a n d metachondromatosis. W e r e p o r t three patients with two peculiar f o r m s o f e n c h o n d r o m a t o s i s w h i c h m a y constitute separate n o s o l o g i c entities.
*Supported by a Grant from the Volkswagen Foundation, and Grant USDHEW/PHS GM20130 from the National Institute of General Medical Sciences. Contributed, in part, as Paper No. 2215 from the University of Wisconsin Genetics Laboratory
1. Enchondromatosis with Irregular Vertebral Lesions Case I P. D. was a 4 year-nld boy referred for evaluation of his physical deformities. His 34 year-old, non-consanguineous parents and 3 half-siblings (2 boys from a previous marriage of the mother and a boy from a previous marriage of the father) were healthy. He was born at term weighing 2400 g and measuring 40 cm. "Growth problems" were noted immediately. Psychomotor development and I Q were normal. At 3 years, a left femoral osteotomy was performed. At 4 years he had a height of 82.5 cm (< 3 %ile),sitting height of 50 cm (50%ile for heigh0, head circumference of 51.2 cm (50 %ile),and bilateral myopia and esotropia, posterior angulation of auricles, short mandible, and protuberant right hemithorax with accentuated costal flare. The liver extended 1.5 cm below the right costal margin. The skin appeared lax and wrinkled. Fine lanugo hair covered part of the trunk and limbs. There was a S-shaped scoliosis and moderate lumbar hyperlordosis. The left leg was 6 cm shorter than the fight. The elbows, wrists, knees and ankles were unusually prominent. The left thigh and left forearm could not be fully extended, but wrist and knee joints were hyperextensible. The feet were flat and forefeet were splayed. Roentgenograms showed enchondromata of the long tubular bones. With the exception of the humeri, the left side was more severely affected than the right (Fig. 1 A, B). Hand films showed only minimal metaphyseal irregularities of the left second and third proximal phalanges. The vertebral bodies were deformed with irregular end plates (Fig. 1 C). The anterior margins of the ribs were dilated with irregular cystic defects. The skull was normal. A review of older films showed that the enchondromatous lesions of the long bones had been present at 4 months.
Discussion. A search o f the literature turned up 3 almost identical cases: a 7 year-old boy [71, a 20 yearold w o m a n followed since birth, (5, case 1), and a 5 year-old girl published as "a micromelic type o f spondylo-meta-epiphyseal dysplasia" . T h e 3 patients and our patient differ from the usual patient with enchondromatosis by 1) the generalized vertebral involvement, and 2 ) t h e discrepancy between
J. Spranger et al.: The Enchondromatoses
Fig. 1 A-C. Patient 1, 4 years. A and B Large cystic masses containing irregular strands of bone and calcifications are seen in the distal metaphyses of the left femur, radius and ulna. Small lesions are present at other sites. Both femora are deformed, the left femur, ulna and radius are shortened and their shafts are slightly expanded. The left capital femoral epiphysis is not ossified; on the right it is irregular. The hands are not involved. C The vertebral bodies are slightly foreshortened and irregularly deformed
the severe involvement of the long bones and the conspicuous absence of enchondromata in the short tubular bones. The abovementioned 3 patients with enchondromatosis and spinal involvement were isolated cases. The parents and a total of 6 siblings of our and Kozlowki's case  were normal.
Examination showed a 2 1/2 year-old boy measuring 89.5 cm (10%ile), weighing 12.9 kg (10%ile), with dolichocephaly, prominent forehead, narrow maxilla with highly arched palate, normal teeth, clear corneae with a diameter of 13 mm (megalocorneae). The patient had a pectus excavatum, short, stubby fingers, and unusually prominent joints. Liver and spleen were not enlarged and there were no herniae. Neurologic and psychologic evaluation gave normal results. Routine laboratory values including serum calcium, phosphorus and alkaline phosphatase were normal.
2. Generalized Enchondromatosis with Mild Platy-
spondyly Case 2 P. S., a male, was born measuring 52 cm and weighing 3500 g. His psychomotor development was moderately retarded; he sat without support at 10 months and walked at 18 months.
S. V., a male, was born weighing 4000 g and measuring 55 cm. The pregnancy was complicated by an EPH gestosis lasting from mens V to IX. His parents, 4 older and a younger siblings were healthy. Parental consanguinity was denied. At about 5 months retarded psychomotor development and prominent finger joints were noted. The patient learned
J. Spranger et al.: The Enchondromatoses
Fig. 2 A and B. Patient 2. A 2 years. There are irregular radiolucent defects of the iliac crest, acetabular roof, the upper margins of the ischiadic bones and the proximal portions of the femoral shafts. Note the symmetry of the lesions. B 21/2 years. The metacarpals and phalanges are short. The metaphyses of the second to fifth proximal and middle phalanges are expanded by radiolucent tumefactions containing variable amounts of irregular strands of bone. The metaphyses of the distal ulna and radius and of the first metacarpal and proximal phalanx are irregularly ossified with cystic radiolucencies extending into the shafts. The distal phalanges and the carpal bones are normal
Table 1. Classification of the enchondromatoses Name of condition
Major radiographic features
State of delineation
1, 2, 5, 7, 9
Multiple enchondromata of the tubular and flat bones, unevenly distributed, in various stages of development, sparing calvaria and vertebrae
II. Maffucci syndrome
Same as Ollier disease, with multiple cutaneous hemangiomata
Multiple enchondromata with prominent marginal or solid calcifications, exostoses, rapid progression and regression, affecting preferably the short tubular bones
Irregular distributed mostly discrete enchondromata of long tubular bones; generalized severe platyspondyly
autosomal recessive ?
V. Enchondromatosis with 3, 5, 7 irregular vertebral present case lesions
Multiple enchondromata of the long tubular and fiat bones, generalized, irregular dysplasia of the vertebral bodies
no hereditary factor known
VI. Generalized Enchondromatosis
Generalized, evenly distributed enchondromata with severe involvement of the hands and feet, mild platyspondyly and skull deformity
no hereditary factor known
2, 10 present case
J. Spranger et al.: The Enchondromatoses
Fig. 3 A-E. Patient 3, 6 years. A Note prominent forehead and symmetrically swollen joints. B The vertebral bodies are moderately flattened with anterior protrusion of their central partlons in the lumbar spine. C The metaphyses of the distal femora and the tibiae are irregularly ossified with longitudinal areas of decreased density being separated by osseous septa. The distal ends of the tibial shafts are slightly expanded. The contours of the epiphyses are irregular. The lateral portions of the right distal tibial epiphysis are not ossified. D The tubular bones are shortened with a bubbly appearance of the metaphyses and submetaphyseal portions of the shafts. Extra ossification centers are present in the second to fifth metatarsals. The contours of the tarsal bones are irregular. E The hand changes are almost identical to those of patient 2 (Fig. 2 C)
J. Spranger et al.: The Enchondromatoses to sit at 18 months and to walk at 4 years. At 5 years a left supravesical ureteral stenosis with secondary hydronephrosis was diagnosed and surgically corrected. At 5 1/2 years he had a height of 96 cm (< 3 %ile), weight of 16.0 kg (10 %ile) and head circumference of 52 cm (50 %ile), a prominent forehead, high-arched palate, small teeth, dysplastic auricles with a hypoplastic helix on the left and a deeply notched antitragus on the right, and a 5 x 5 cm large capillary hemangioma over the right buttock. The lumbar lordosis was accentuated, and the interphalangeal joints, wrists, knees and ankles were unusually prominent (Fig. 3 A). His gait was broad-based and clumsy. Muscle tone, motor coordination, muscle reflexes and joints mobility were normal. The patient did not speak spontaneously but imitated sounds and words. A Denver test showed a developmental age of 2 years. An audiogram was normal. Routine laboratory values including serum calcium, phosphorus, alkaline phosphatase, BUN, electrolytes, urinary protein, amino acids and mucopolysaccharides were normal. The radiographic findings in the two patients were almost identical. The neurocranium was dolichocephalic. The vertebral bodies were mildly flattened with regular end plates (Fig. 3B). The iliac crests, acetabular roofs, ischiae and proximal portions of the femoral shafts appeared eroded by numerous cystic lesions (Fig. 2 A). There were mild metaphyseal irregularities in the knees and moderately severe enchondromatous lesions in the distal metaphyses of the tibiae (Fig. 3 C). The most prominent changes were present in the hands and feet (Fig. 2 B, 3 D, E) with enchondromatous lesions of varying degree in most tubular bones. The enchondromata were symmetrically distributed and in similar stages of development. There was widespread, but mild involvement of the epiphyses and tarsal bones.
Discussion. A search of the literature turned up 3 similarly, though more severely affected patients [2, 10]. Together with our cases they differ from the c o m m o n type of enchondromatosis by the following features: 1) The involvement of almost all metaphyses of the long and particularly of the short tubular bones. The enchondromatous lesions are in almost the same stage of development leading to the regular, metaphyseal-chondrodysplasia-like appearance of the bones. However, it should be noted that the distal phalanges of our patients and the left femur and tibia of Fairbank's patient  were less affected than other bones. 2) The presence of bone changes apparently unrelated to the enchondromatous process such as platyspondyly and skull changes. The reported cases were unrelated and no similar cases were present in their families.
The enchondromata in Ollier disease appear to be the result of regionally confined dysplasias. In contrast, the newly delineated types of enchondro-
matosis display strong elements of a generalized dysplasia such as the systemic vertebral changes and the symmetric metaphyseal involvement in one of them. These elements of a general bone dysplasia can be so prominent that a metaphyseal chondrodysplasia may be diagnosed [3, 10]. However, radiographically the basic lesions are enChondromata and itis in the group of enchondromatoses where the 2 disorders should be classified (Table 1). The lack of etiologic or pathogenetic clues precludes a decision whether we are dealing with variable expressions of one and the same disorder or with different entities. At our present stage of knowledge it appears justified and necessary to report two different phenotypes and to point to the possibility of further heterogeneity of the enchondromatoses cited in Table 1. References 1. Bethge, J. F. J.: Die Olliersche Krankheit. Dtsch. Med. Wochenschr. 87, 535 (1962) 2. Fairbank, H. A.: Dyschondroplasia. J. Bone Joint Surg. [Br.] 30, 689 (1948) 3. Kozlowski, K.: Micromelic type of spondylo-meta-epiphyseal dysplasia. Pediatr. Radiol. 2, 61 (1974) 4. Lewis, R. J., Ketcham, A. S.: Maffucci's syndrome: functional and neoplastic significance. J. Bone Joint Surg. [Am.] 55, 1465 (1973) 5. Mainzer, F., Minagi, H., Steinbach, H. L.: The variable manifestations of enchondromatosis. Radiology 99, 377 (1971) 6. Maroteaux, P.: La m6tachondromatose. Z. Kinderheilkd. 109, 246 (1971) 7. Rubin, P.: Dynamic Classification of Bone Dysplasias, p. 214. Chicago: Year Book Medical Publishers 1964 8. Schorr, S., Legum, C., Ochshorn, M.: Spondyloenchondrodysplasia. Radiology 118, 133 (1976) 9. Spranger, J., Langer, L. O., Wiedemann, H. R.: Bone Dysplasias. An Atlas of Constitutional Disorders of Skeletal Development. Stuttgart, Chicago: Fischer/Saunders 1974 10. VanCrefeld, S., Kozlowski, K., Petron, K., van der Valk, A.: Metaphyseal chondrodysplasia calcificans. Br. J. Radiol. 44, 773 (1971)
Date offinal acceptance: May 30, 1978
Prof. Dr. J. Spranger Universitgts-Kinderklinik Langenbeckstral3e 1 D-6500 Malnz Federal Republic of Germany