American Journal of Medical Genetics 78:61–66 (1998) A Rare Form of Spondylometaphyseal Dysplasia-Type A4 T. Duetting,1* A. Schulze,2 J. Troeger,1 and J. Spranger3 1 Department of Pediatric Radiology, Ruprecht-Karls University, Heidelberg, Germany Department of Pediatrics, Ruprecht-Karls University, Heidelberg, Germany 3 Department of Pediatrics, Johannes Gutenberg University, Mainz, Germany 2 We present 2 cases of a previously apparently unreported spondylo-metaphyseal dysplasia comprising dwarfism, severe metaphyseal changes, ovoid vertebrae and mild platyspondyly with anterior tonguing of the vertebral bodies. The inheritance may be autosomal recessive. Am. J. Med. Genet. 78:61–66, 1998. © 1998 Wiley-Liss, Inc. a classification scheme [Maroteaux, and Spranger, 1991], but no detailed descriptions were provided. This is an attempt to more clearly delineate this form of spondylometaphyseal dysplasia. KEY WORDS: bone dysplasia; spondylometaphyseal dysplasia; dwarfism; platyspondyly; autosomal recessive inheritance; coxa vara deformity A 12 6/12 month old Turkish boy was admitted because of short stature. He is the first child of seconddegree consanguineous parents. Intrauterine growth appeared somewhat retarded until the 7th month of pregnancy, but was compensated at birth. Birth was at term with a weight of 2,500 g, a length of 48 cm and a head circumference (OFC) of 33 cm. Delivery and postnatal development were uneventful, except for progressive shortness. On presentation in our hospital at the age of 12 6/12 months, the boy’s weight was 7 kg, his length 61 cm, both below the 3rd centile. The OFC was 47 cm. Shortness was disproportionate affecting the limbs more than the trunk. Psychomotor and neurological development were normal; the child stood and walked without support. Results of routine laboratory tests were normal. At the age of 23 months, weight was 8,330 g, length 66 cm, and OFC 48 cm. Clinically the boy showed a coxa vara deformity with a waddling gait. INTRODUCTION The spondylometaphyseal dysplasias are a heterogenous group of disorders characterized by vertebral changes and abnormal radiographic appearance of the metaphyses. These changes appear in various forms with different severity [Taybi and Lachman, 1996]. Best known and most common are the types named after Kozlowski [Kozlowski et al., 1967, 1976; Lachman et al., 1979; Michel et al., 1970; Riggs et al., 1971], Schmidt-Sutcliffe (corner fracture type) [Langer et al., 1990; Schmidt et al., 1963; Sutcliffe, 1966], and Sedaghatian [Peeden et al., 1992; Sedaghatian, 1980]. Many other forms were described in single reports and manifest a great complexity. Lachman [Taybi and Lachman, 1996] divided them into uncommon [Kozlowski et al., 1988; Murdock et al., 1969] and rare types [Bagga et al., 1989; Borochowitz et al., 1988; Campbell et al., 1992; Felman et al., 1974; GarciaCastro et al., 1982; Goldblatt et al., 1991; Gustavson et al., 1978; Hasegawa et al., 1994; Horton et al., 1983; Kozlowski et al., 1976, 1979]. Here we report on two patients with the same form of a spondylometaphyseal dysplasia. This type has previously been mentioned in *Correspondence to: Dr. Med. Tanja Duetting, Department of Pediatric Radiology, Ruprecht-Karls University, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany. Received 21 January 1998; Accepted 26 March 1998 © 1998 Wiley-Liss, Inc. CLINICAL REPORTS Patient 1 Patient 2 This patient, a girl, is the first child of nonconsanguineous parents, both of whom have 4 brothers or sisters. There was no family history of dwarfism, nor any other genetic disorder. Pregnancy was normal, delivery in the 37th week from a breech position. Birth weight was 2,360 g, length 46 cm. On examination at age 19 months, a weight of 8,310 g, a length of 68.7 cm and a OFC of 47.2 cm were measured. She had shortlimb dwarfism especially of lower limbs. Motor and neurological examination showed no abnormal findings, routine laboratory findings were normal. At the age of 4 3/12 years weight was 12.9 kg and length 84 cm. Except for the known deformities of the limbs and clinodactyly of the 5th fingers, no clinical abnormalities were recorded. Laboratory data were normal. Fig. 1. Fig. 1. Patient 1, boy at 12 and 23 months of age A. (12 months): AP view of pelvis and hips. The iliac wings are somewhat squared with a decreased cranio-caudal dimension and narrow sacrosciatic notches. The acetabular roofs are horizontal with a separate medial notch, the ischia are broad. The femoral neck is dysplastic with mildly delayed ossification and a markedly widened physis, the angle between shaft and neck is about 150 degrees. The metaphyseal margin is irregular with a bigger, nearly shaftwide fragment lying over the metaphyseal plate (subepiphyseal plate-pseudofracture), on both sides. The epiphyses appear slightly small, normally formed and well ossified. B. (12 months): AP view of left lower limb. The distal femoral and proximal tibial metaphyses are widened with an irregular sclerosed contour of the endplates and a small fragment on the medial margin of the tibia, appearing like a corner fracture. The shafts are shortened. C. (23 months): AP view of left lower limb. The metaphyses have an undulating, irregular contour, the metaphysis of the femoral neck is fragmented, the angle between shaft and neck is about 130 degrees with a developing coxa vara deformity. Mild genu varum deformity is also present. D. (12 months) and E. (23 months): AP view of left upper limb. The metaphysis of the short humerus is widened, with a smoothly undulating margin. The metaphyses of the distal radius and ulna are widened and cupped. F. (12 months) and G. (23 months): AP view of left hand. The tubular bones of the hand are short and broad with moderate concave alteration of the metaphyses, metaphyseal widening and disassociational carpal ossification delay. Bone age and mineralization are normal. H. (12 months) and I. (23 months): Lateral view of spine. There is a slightly accentuated lumbar lordosis and possibly a developing thoraco-lumbar junctional area kyphosis. The vertebral bodies have an ovoid form with prominent anterior tonguing. Platyspondyly is quite mild. Fig. 2. SMD-Type A4 65 These changes were most marked in the femoral neck (Fig. 1A,C). In the pelvis, the iliac wings were short in their cranio-caudal dimensions with narrow sacrosciatic notches, horizontal, poorly formed acetabular roofs and broad ischia (Fig. 1A; Fig. 2A). The femoral neck was underossified with a very wide physis, an irregular metaphysis and a slightly small proximal femoral epiphyseal ossification center. Radiographically there was no significant coxa vara deformity (Fig. 1A; Fig. 2A,B). The spine showed mild (Fig. 1H,I; Fig. 2G) platyspondyly with a slightly accentuated lumbar lordosis, which aggravated until the 4th year in patient 2, whereas platyspondyly did not progress (Fig. 2H). The vertebral bodies had an ovoid form with anterior tonguing (Fig. 1H,I; Fig. 2G,H). In the hands, the metaphyses of the short tubular bones had mild cupping and widening in one and severe cupping and flaring in the other, and the diaphyses were short (Fig. 1F,G; Fig. 2E,F). The bone age in patient 2 was dissociated with retarded ossification of the carpal bones and accelerated epiphyseal development with similar epiphyseal/carpal dissociation in the other without epiphyseal acceleration (Fig. 2E,F). In the thorax, the anterior ends of the ribs were broad and irregular; lung and heart appeared normal (Fig. 1H). The skull was normal (not shown). DISCUSSION Fig. 2. Patient 2, girl at 19 months of age and 4 3/12 years of age A. (19 months): AP view of pelvis and lower limbs. The iliac wings are somewhat squared with horizontal acetabular roofs and narrowing of the sciatic notches. The ischia are broad. The femoral neck is quite short with an angle between the shaft and neck of about 145 degrees. The capital femoral epiphysis is somewhat small and there is very significant physeal widening present. Distally the metaphyses are broadened with irregular outlines, less marked than in patient 1. The diaphyses are short, the knee epiphyses are normal. B. (4 3/12 years): AP view of left lower limb. The physis is less wide and the capital femoral epiphysis is still small. The angle between shaft and neck is still 145 degrees, there is no varus-deformity. C. (19 months) and D. (4 3/12 years): AP view of left upper limb. The long tubular bones are short, more proximally than distally. The humeral diaphyseal expansion is pronounced at 19 months, and less striking at 4 3/12 years. The metaphyses are deformed. The contour of the metaphyses of the proximal humerus and of the distal radius and ulna is irregular and undulating. E. (19 months): AP view of left hand. The metaphyses are severely cupped, the tubular bones are short and broad. The bone age is significantly dissociated, with no ossification of the carpal bones, but with acceleration of the ossification of epiphyseal centers. The mineralization is normal. F. (4 3/12 years): AP view of left hand. There is a progression of cupping and epiphyseal accelerated ossification and still significant carpal/epiphyseal dissociation. G. (19 months): Lateral view of spine. The spine shows a slightly accentuated lumbar lordosis and ovoid vertebral bodies with anterior tonguing. A single lumbar intervertebral disc is calcified (arrow). H. (4 3/12 years): Lateral view of spine. The mild platyspondyly is not progressive, there is only a mild aggravation of lumbar lordosis, but no scoliosis. The disc calcification seems to have resorbed. Radiologic Evaluation The radiographic manifestations of both cases can be summarized as follows: The long bones and short tubular bones of the hands were short, more proximally than distally, the metaphyses were widened (Fig. 1D,E; Fig. 2C), partly irregular and fragmented with the occasional appearance of ‘‘corner fractures’’ (Fig. 1B). This spondylometaphyseal dysplasia presents with a short limb type dwarfism in the second year of life. The proximal tubular bones seem to be more affected than the mesial and distal ones. Neurological and mental development are normal. Scoliosis was not present until the 5th year of life in one, but there was a mild accentuation of lumbar lordosis in both. Coxa vara deformity with waddling gait seems to be mild in early life but presumably becomes more pronounced. Parental consanguinity, observed in the first patient, suggests an autosomal recessive inheritance pattern. Radiographically, this is a moderately severe spondylometaphyseal dysplasia with characteristic proximal femoral physeal (growth plate) widening and ovoid, anteriorly tongued pointed vertebral bodies with more severe long bone metaphyseal changes in case 1 but milder hand changes. We suggest this is clinical variability in the same skeletal dysplasia. The entity has so far not been fully delineated in the literature, but our patient 2 was the prototype of type A4 of the classification of Maroteaux and Spranger . In this classification (Table I), type A4 refers to a form with severe metaphyseal changes of the femoral neck and flattened vertebral bodies with tongue like deformity as apparent in these patients. Metaphyseal progression only occured in case 1, while the mild long bone metaphyseal involvement in case 2 as well as the severe hand changes with ossification dysharmony and epiphyseal maturation acceleration were not listed in the classification as diagnostic attributes. The present cases can easily be differentiated from the common forms of spondylo-metaphyseal dysplasia: The Kozlowski type [Kozlowski et al., 1967] has accen- 66 Duetting et al. TABLE I. Classification of Spondylometaphyseal Dysplasias By Maroteaux and Spranger  (Modified) Severe changes of the femoral neck: • A1: Mild vertebral abnormalities, discrete metaphyseal changes • A2: Mild vertebral abnormalities, more severe metaphyseal changes • A3: Round vertebral bodies, severe metaphyseal changes like A2 • A4: Ovoid, flattened vertebral bodies with anterior tongue like deformity Moderate changes of the femoral neck: • B1: Slight irregularity of the vertebral bodies, short tubular bones of the hand with irregular metaphyses • B2: Generalized platyspondyly (close to brachyolmy) Discrete changes of the femoral neck: • C1: Squared form of the vertebral bodies with irregular contour • C2: Moderately flattened and long vertebral bodies • C3: Trapezoidal aspect of the vertebral bodies tuated kyphoscoliotic changes and less severe metaphyseal alterations. An autosomal dominant inheritance is apparent. In contrast to the corner fracture type [Langer et al., 1990], our cases also show mostly smoothly limited metaphyses, small iliac wings and different spine changes. Of the uncommon and rare forms, the Algerian type [Kozlowski et al., 1988] is marked by severe kyphoscoliosis and genu valgum deformity. Murdock and Walker’s patient [Murdock, Walker, 1969] had sclerotic vertebral end plates, no or mild platyspondyly, genua valga and severe metaphyseal changes. In the Borochowitz type [Borochowitz et al., 1988], the metaphyseal and vertebral changes are less severe than in our patients. In brachyolmia [Horton et al., 1983], only minimal to no metaphyseal changes are noted, the Japanese type [Hasegawa et al., 1994] shows moderate platyspondyly but only mild metaphyseal involvement. Gustavson et al.  described a form with similar metaphyseal changes but only moderate platyspondyly without anterior tonguing and only minimal changes in the hands. 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