I Med Genet 1990; 27: 467-471

Mlicrospherophakia-metaphyseal dysplasia:a 'new' dominantly inherited bone dysplasia with severe

eye involvement

Alain Verloes, Lionel Van Maldergem, Pierre de Marneffe, Jean-Louis Dufier, Pierre Maroteaux

AbstractWe report a father and son affected by a hithertounpublished bone dysplasia with moderately severedwarfism. On initial radiographs, thickening of thediaphyses of the long bones was striking. The smallbones of the extremities were almost unaffected.With age, the metaphyseal deformation becamemore prominent. The epiphyses became irregularand their growth was delayed (particularly thefemoral heads). The femoral neck showed anunusual 'lip' on the inner edge. Later, the stubbyappearance of the long bones faded and, in adult-hood, only enlarged metaphyses and deformedfemoral necks persisted. The vertebrae showedmoderate deformation with irregular flattening,and narrowing of the spinal canal with a shortenedinterpedicular distance. The eye defects consistedof high grade myopia, microspherophakia, lenscoloboma, lens luxation, and retinal detachment.The name 'microspherophakia-metaphyseal dys-plasia' is suggested for this probably autosomaldominant bone dysplasia.

Among the still growing number of bone dysplasias,brachymelia with thick diaphyses represents apuzzling and poorly classified group. We report afather and his son affected by a metaphysodiaphysealdysplasia complicated by high myopia, which couldrepresent an undescribed bone dysplasia.

Case reportsCASE 1Case 1 (Genetic file no 4056) was born in 1983 to non-consanguineous parents. His mother was 30 andoriginated from the Philippines. Birth length was43 cm, birth weight 2400 g, and OFC 33-8 cm. Wesaw him for the first time at the age of 31/2 when hisfamily was referred for diagnostic advice.

Physical examination of this boy showed micro-melic dwarfism. He was 73 cm tall. The face wasround and somewhat flat. The trunk was short, withpigeon breast and bell shaped thorax (fig 1). Lumbar

Centre for Human Genetics, University Hospital, Liege,Belgium.A Verloes

Centre for Human Genetics, Loverval, Belgium.L Van Maldergem

Department of Rheumatology, University Hospital,Liege, Belgium.P de Mameffe

Department of Ophthalmology, H6pital Laennec, Paris,France.J-L Dufier

Clinic of Medical Genetics, H6pital des Enfants Malades,Paris, France.P MaroteauxCorrespondence to Dr Verloes, Centre de Genetique, Patho-logie B23, CHU Sart Tilman, 4000 Liege, Belgium.

Received for publication 25 January 1990.Accepted for publication 22 February 1990.

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Figure I Patient I at 3112years.

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Figure 2 Patient l at 3l2years. Notefemoral neck shape andprobable fracture ofinner tibial plates. Figure 4 Patient 1 at 5years. Hyperlordosis and abnormal

vertebral shape.

Figure 5 Patient I at Syears. Constraint fractures.

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F' re3 Patientlat3il2years.Upperlimb.

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M a 'newz' dominantly inherited bone dysplasia with severe eye involvement

Figure 6 Patient 2 at 43years. Enlargedepimetaphyseal region.

hyperlordosis was prominent. The upper limbs wereshort but there was no limitation of movement in thejoints. The lower limbs were bent. Hip extension androtation were restricted. There was genu varum with aslight recurvatum and inward bowing of the tibiae.The hands and feet were not shortened.

Radiographs showed severe involvement of the longbones (fig 2). The femora and tibiae were very stubbyand there was cortical thickening. The lower femoral,upper and lower tibial, and humeral metaphyses wereenlarged and densified. Their edge was irregular andslightly convex. The epiphyses were irregular andunderdeveloped. Enlargement of the femoral necks

was striking. Their inner edge showed a thick,horizontal 'lip' (fig 2). The femoral heads were smalland flattened. Acetabular roofs and the pelvis werenormally shaped. There was hyperlordosis but thevertebrae were normally shaped. The only anomalyon hand x rays was pseudoepiphysis of the secondmetacarpal bone (fig 3).

Ophthalmological investigations showed a normalcorneal diameter, deep anterior chamber, micro-spherophakia, right lens coloboma, superoexternallens luxation on the left side and posteronasal luxationon the right side, and bilateral partial lens opacification.Visual acuity was 0-4 on the right and 0-1 on the left,and myopia was rated at -4 to -5 dioptres bilaterally.

His development was marked by progressiveaggravation of the genu varum. At 51/2 years, he was80 cm tall. X rays disclosed more irregular vertebrae(fig 4), and spontaneous, bilateral, sloping fractures ofthe inner part of the tibial metaphyses, alreadysuspected earlier, but probably promoted by themechanical constraints of the varus deformity (fig 5).Small fractures of the lateral aspects of the lowerfemoral epiphyses were also visible. Femoral osteo-tomy was performed. The cataracts worsened andwere surgically corrected at the same time. Psycho-motor development was normal. Homocystinuria wasexcluded.

CASE 2Case 2 is the father of case 1. He was born in 1946to non-consanguineous, unaffected parents. Thediagnosis of achondroplasia was suggested duringchildhood. He had high grade myopia, which wasrated at -11 to -12 dioptres bilaterally at 11 years,when the first retinal detachment occurred. Ocularhypertension was observed at 27 years, and subtotalblindness owing to retinal detachment was present at

Figure 7 Patient 2 at 43years.Square pelvis.

Ml-crospherophaki-a-metaphyseal dysplasta: 469

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Figure 8 Patient 2 at 43years. Wedge shaped vertebral bodies,narrow medullary canal, and spondylarthrosis.

Figure 9 Patient 2 at 43years. Note insufficient interpediculardistance.

the age of 30. Coronal and zonular opacities of the lenswere noted, but microphakia or spherophakia werenot mentioned in the records. Recently, light per-ception has been improved by partial lens dislocation.When we saw him at the age of 41, he was 139 cm

tall, with micromelia and a shortened, bell shapedthorax. Limb deformation was less marked than in hisson. He complained of hip pain. No prepubertalx rays could be found. On adult pictures, enlargedepimetaphyses were visible (fig 6). The pelvis wassquare and acetabular roofs were not horizontal. Thefemoral heads were enlarged with bilateral coxa vara(fig 7). The vertebral plates were irregular and thelesions were more severe at the thoracic level;vertebrae D6, D9, and LI were wedge shaped (fig 8).The spinal canal was narrowed on side view. On frontview, the interpedicular distance was narrowed anddid not increase in the lower lumbar vertebrae (fig 9).

DiscussionThe family reported here showed a unique pattern ofbone defects. On initial radiographs, the diaphysealthickening was striking in the long bones, though thesmall bones of the extremities remained almostunaffected. With age, the metaphyseal deformationbecame more prominent, epiphyseal irregularitiesoccurred, and the femoral neck showed an unusual'lip'. Later, the stubby appearance of the long bonesfaded and, in adulthood, only enlarged metaphysesand deformed femoral necks persisted. The vertebraeshowed moderate deformation.Few bone dysplasias are associated with lens

anomalies. In Kniest spondyloepiphyseal dysplasiacongenita,' there is typical metaphyseal swelling andsevere delay of epiphyseal ossification. Cleft palateis common. The same retardation in epiphysealmaturation is observed in 'common' spondylo-epiphyseal dysplasia. Stickler syndrome,2 3 theneonatal Weissenbacher-Zweymuller syndrome,4Wagner hyalidoretinal degeneration,5 Marshallsyndrome,6 and micrognathic dwarfism7 are clinicalexpressions of a complex family of bone dysplasias(commonly called as a whole Stickler syndrome,although their exact nosology and delineation remainscontroversial''0). Most of them show a moderatemetaphyseal involvement. A common feature is the,high grade myopia with frequent retinal detachment.Weill-Marchesani syndromel" associates micro-spherophakia and stunted growth. Bone anomaliesinclude brachydactyly, moderate shortness of the longbones, and slight vertebral deformation. Inheritanceis autosomal recessive, although shortness of stature issometimes reported in parents. Chondrodysplasiacalcificans metaphysealis is characterised by shortstature, progressive deformity, metaphyseal dysplasiawith calcium deposit, and myopia.'2 Myopia is also a

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M crospherophakt'a-metaphyseal dysplasia: a!'new' dominantly inherited bone dysplasia with severe eye involvement

feature of dysosteosclerosis,13 which includes general-ised osteosclerosis, platyspondyly, submetaphysealtranslucencies, and ectodermal changes. The radio-logical pictures of our two cases do not fit any of thesesyndromes.The cases reported here may be considered as

expressing a 'new' bone dysplasia with severe eyeinvolvement. We suggest it should be called micro-spherophakia-metaphyseal dysplasia. Autosomaldominant inheritance is likely.

1 Maroteaux P, Spranger J. La maladie de Kniest. Arch Fr Pediatr1973;30:735-50.

2 Stickler GB, Belau PG, Farrell FJ, et al. Hereditary progressivearthro-ophthalmopathy. Mayo Clin Proc 1%5;40:433-55.

3 Herrmann J, France TD, Spranger JW, Opitz JM, Wiffler C.The Stickler syndrome (hereditary arthroophthalmopathy).Birth Defects 1975;11(2):76-103.

4 Weissenbacher G, Zweymuller E. Gleichzeitiges Vorkommen

eines Syndroms vom Pierre Robin und einer fetalen chondro-dysplasie. Monatsschr Kinderheilkd 1964;112:3 15-7.

5 Jansen LMAA. Degeneration hyaloideo-retinalis hereditaria.Ophthalmologica 1%2;144:458-64.

6 Marshall D. Ectodermal dysplasia: report of a kindred withocular abnormalities and hearing defect. Am Ophihalmol1958;45: 143-56.

7 Maroteaux P, Roux C, Fruchter Z. Le nanisme micrognathe.Presse Med 1970;78:2371-4.

8 Winter R, Baraitser M, Laurence KM, Donnai D, Hall CM. TheWeissenbacher-Zweymuller, Stickler and Marshall syndromes:further evidence for their identity. Am J Med Genet 1983;16:189-99.

9 Ayme S, Preus M. The Marshall and Stickler syndromes:objective rejection of lumping. Med Genet 1984;21:34-8.

10 Libefarb RM, Hirose T, Holmes LB. The Wagner-Sticklersyndrome: a study of 22 families. Pediatr 1981;99:394-9.

11 Ferrier S, Nussle D, Friedli B, Ferrier PE. Le syndrome deMarchesani (spherophakie-brachymorphie). Helv Paediatr Acta1980;35:185-98.

12 Van Creveld S, Kozlowski K, Pietron K, Van der Valk A.Metaphyseal chondrodysplasia calcificans. A report of twocases. BrJ Radiol 1971;44:773-9.

13 Spranger JW, Albrecht C, Rohwedder HJ, Wiedemann HR. Diedysosteosklerose: eine sonderform der generalisierten osteo-sclerose. Fortschr Roentgenstr 1%8;109:504-12.

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