K. Kozlowski J. Masel
Mesomelic dysplasia with periosteal thickening,radio-humeral dislocation, osteoporosisand multiple fractures
Received: 3 April 1998 /Accepted in revised form: 7 September 1998
Abstract We report a boy with a new form of mesomelic dysplasia characterised by shortstature, multifocal periosteal thickening, radio-humeral dislocation, osteoporosis andmultiple fractures with minimal trauma. Electrophoresis of fibroblast collagens detecteddefects in type III and type V collagen.
Conclusion Bone dysplasias presenting with osteopenia, abnormal trabecular pattern,bone fragility, and periosteal thickening suggest a collagenopathy. A possible collagendefect requires biochemical investigations.
Key words Mesomelic dysplasia Periostitis Radio-humeral dislocation Osteoporosis Collagenopathy
Abbreviation MD mesomelic dysplasia
Mesomelic dysplasia (MD) is a heterogenous group ofinherited bone disorders characterised by dispropor-tionate shortness of the middle segment of the extremi-ties. Dierent patterns of tibia/fibula and ulna/radiusshortening, involvement of other parts of the skeletonand/or other parts of the body (eyes,kidneys,brain) haveresulted in dierentiation of more than twenty dierenttypes of MD .
The most common type of MD is dyschondrosteosis.Otherwell dierentiated types are that ofLanger ,Nievergelt , Reinhard-Pfeier , Werner , andRobinow . The Maroteaux  and Campailla-Martinelli  types are characterised by hand and footinvolvement. The patients reported by Kozlowski et al andReardon et al  are characterised bymesomeliaof the upper extremities with other distinctive anomalies.
The remaining forms are rare, represented by single cases,few cases or single families [1, 37, 9, 14, 2024].
We report another patient with unclassified MD(Fig. 1). The unique features, besides mesomelic short-ening of the extremites, were osteoporosis, abnormaltrabecular pattern, multiple fractures, periosteal thick-ening and radio-humeral dislocation.
This boy was born to young, healthy parents after a full term,uncomplicated pregnancy and delivery. There was no parentalconsanguinity, no history of hereditary diseases or malformationsin the patients family. A brother and two sisters of the patient arenormal. The patients birth weight was 2.6 kg and he was noted tobe short.The skeletal survey showed shortening of the extremitiesand normal skull. These changes were felt to be consistent withachondroplasia. At the age of 2.5 years he sustained a fracture ofthe left fibula and a year later a fracture of the 3rd and 4th right
Eur J Pediatr (1999) 158: 308 311 Springer-Verlag 1999
K. Kozlowski (&)1
Department of Radiology,Royal Alexandra Hospital for Children, Sydney, Australia
J. MaselDepartment of Radiology, Royal Childrens Hospital,Brisbane, Australia
Present address:1New Childrens Hospital,P.O. Box 3515 Parramatta, NSW 2124, Australia
Fig. 1 16 years old. Normal face
Fig. 2 AE 8 years old. A,B Mesomelic shortening of the extremities. Periosteal thickening with the ulna being most severely aected.Abnormal trabecular pattern. C Periosteal thickening of the metatarsals. Osteopenia. D Bowed femora. Coxa valga. Abnormal trabecularpattern. E 15 years old. The tubular bones of the hands are shortened and wide. The proximal phalanges are most severely aected. Periostealthickening of the metacarpals and to a much lesser degree of the proximal and middle phalanges. Abnormal trabecular pattern. F 16 years old.Deformed left femur with ununited mid-shaft fracture. Abnormal trabecular pattern
metatarsals. Radiographs performed 4 months later showed de-layed healing of the fractures and the diagnosis of achondroplasiawas abolished. At the age of 5 years and 2 months fractures of theright humerus and left ulna occurred.
He was assessed in the Royal Childrens Hospital at the age of 5years and 5 months. His height was 90 cm ()4.5 SD). His face wasnormal. He showed short extremities with the middle segment be-ing most severely aected. His primary teeth were said to havecrumbled but the secondary teeth appeared to be normal. Radio-graphic examination documented that all the tubular bones wereshortened but those of the middle segments were most severelyaected. They were short and wide with thick cortex and periostealthickening. The upper ends of radius and ulna and the lower tibialarticular surface and adjacent talus were rounded. The radius wasdislocated posteriorly. There were healing fractures of the rightupper humerus and olecranon process of the left ulna. There wasmoderate generalised osteopenia and abnormal trabecular pattern.Radiographic measurements of the long bones in comparison withthe normal standards  were as follows: humerus 69%, femur70%, ulna 57%, radius 54%, tibia 58%, fibula 59%.
At the age of 7 years his height was 102 cm ()4.2 SD) andweight 17.5 kg ()2 SD). His head, face, ears and hair were normal.The sclerae were white. The palate, tongue and teeth were normal.The skin was normal. The ophthalmological examination showedno abnormality. His big toes were short and broad. The internalorgans were unremarkable and the external genitalia were normal.Mental development was slightly delayed.
The radiographic examinations performed at the ages of 8 and15 years documented persistence of the mesomelic shortening of theextremities (Fig 2AD). The shafts of the ulnae and tibiae werethick. There was some widening of the shaft of the fibula but that ofthe radius returned to normal. The upper end of the forearm bonesremained malformed. The dislocation of the radius at the elbowjoint persisted. The lower tibial articular surface and adjacent taluswere rounded. There was irregular periosteal thickening of themetacarpals and metatarsals. The lower thoracic and upper lumbarvertebrae were biconvex with posterior wedging and there wasspondylolisthesis of L5. Bone density was decreased and the tra-becular pattern was irregular. There was a healing fracture in themid-shaft of the left tibia at the age of 8 years and an un-unitedfracture of the left femur. There was increase of the osteoporosis atthe age of 15 years. The skull and the cervical spine were normal.The chest and pelvis showed no gross abnormality.
Between 1517 years of age he sustained fractures of the rightfemur, left femur, right tibia, and right patella, all after minortrauma (Fig 2E).
Biochemical investigations at the age of 15 years showed serumcalcium levels of 2.522.56 mmol/l (normal 2.152.55), slightly in-creased serum phosphate levels 1.521.63 mmol/l (normal0.801.50), and a low serum creatinine 0.050.06 mmol/l (normal0.060.12). All other biochemical investigations including alkalinephosphatase and serum proteins were normal. The routine bloodand urine examinations were normal. His karyotype was normal46XY.
He was again seen at the age of 18 years. His height was136 cm ()6.2 SD) and weight 60 kg (2550 percentile). Serumcalcium and phosphate values were normal. Preliminary bio-chemical analysis of fibroblast collagens indicated that while typeI collagen was normal in amount and electrophoretic migration,type III collagen was reduced and type V collagen 2(V) chain hadan abnormal electrophoretic migration (Bateman and Chan, un-published results).
Disproportionate shortening of the middle segments ofthe extremities in relation to the proximal and distalsegments fulfills the criteria of MD. Unusual features inthis case were osteopenia, periosteal thickening, multi-ple fractures with minor trauma and delayed healing,
and radial dislocation at the elbow joint. Injuries pre-ceding the fractures included dropping a toy on his foot,kicking a football and climbing into a four-wheel drivecar.
Multiple fractures are a feature of many bone dys-plasias and many metabolic bone disorders with os-teopenia including osteogenesis imperfecta, idiopathicosteoporosis, geroderma osteodysplastica and osteo-porosis-pseudoglioma syndrome. All of them showosteopenia and tendency to multiple fractures but noneof them presents with mesomelia and radial dislocationat the elbow joint. Abnormal skull in osteogenesisimperfecta, senile facies and thin skin in gerodermaosteodysplastica, later appearance of clinical symptomsin idiopathic osteoporosis and blindness in osteoporo-sis-pseudoglioma syndrome and absence of mesomelicshortening in all of them excluded those diagnoses onclinical criteria alone. All the osteosclerotic bone dis-orders which show multiple fractures were rejected, asosteosclerosis was never a feature in our case. The mostcommon metabolic disorders with osteoporosis andoccasional fractures in childhood are vitamin D defi-ciency rickets and hypophosphataemic rickets. Therewere neither clinical, biochemical or radiographic fea-tures of rickets. The diagnosis of hypophosphataemicrickets is unacceptable as bowing of the long bones wasabsent in our patient, the values of serum phosphatewere slightly increased and the serum alkaline phos-phatase was normal. Finally, mesomelic shortening ofthe extremities and radial dislocation are not a featurein either of them. There were neither clinical, radio-graphic or biochemical data suggestive of parathyroidor renal disease.
The subtle biochemical abnormalities, periostealthickening severe osteopenia with multiple fractures,delayed bone healing and radial head dislocation areprobably related to the collagen defects. What the rela-tion is between the mesomelic shortening of the ex-tremities and relevant, preliminary abnormal collagenfindings in our patient we do not know. The unusualclinical history and unique pattern of bone changes al-lows us to designate the disease as a new form of MD.However, we cannot exclu