American Journal of Medical Genetics 35219-221 (1990)
Brief Clinical Rkport Spondylocostal Dysostosis: Dominant Type Peter Lorenz and Edgar R u p p r e c h t Departments of Clinical Genetics (P.L.) and Pediatrics (E.R.), Medical Academy Dresden T a r 1 Gustau Carus,” Dresden, German Democratic Republic We report on a f a t h e r and daughter who h a v e spondylocostal dysostosis. The girl’s ribs are more severely abnormal than those of the 2 previously reported cases of dominant spondylocostal dysostosis and are rather suggestive of the autosomal recessive type. T h e differential diagnosis of both forms is discussed. KEY
WORDS: polydysspondylia, JarchoLevin syndrome, LavyPalmer-Merrit syndrome, costovertebral dysplasia, spondylothoracal dysplasia, multiple hemivertebrae, spondylocostal dysplasia, oc-
cipito-facial-cervico-thoracoabdomino-digital syndrome, autosomal dominant inheritance, autosomal recessive inheritance
INTRODUCTION Spondylocostal dysostosis (SCD) is characterized by multiple malformations of ribs and vertebrae. Cleft, fused, wedge-shaped, and hemivertebrae may occur. The ribs may vary in number and shape or be synostotic, primarily near the costovertebral joints. These malformations are the result of presumed segmentation defects of the axial skeleton. As there are no defects of the neural tube, a defective anlage of the notochord seems to be the underlying pathogenetic defect. Shortness of neck and thorax and a bulging abdomen are obvious manifestations of the disorder. Kyphoscoliosis is common. A typical shape of the cranium with protruding occiput, a typical physiognomy, muscular hypotonia, and herniation have been described. The first comparable observation originates from Bar Fkceived for publication November 22, 1988; revision received August 8, 1989. Address reprint requests to D.M. Peter Lorenz, Department of Clinical Genetics of the Medical Academy Dresden “Carl Gustav Carus”, Fetscherstr. 74, Dresden, DDR-8019, GDR.
0 1990 Wiley-Liss, Inc.
[19031. About 172 patients have been published under various synonyms, 78 cases of the autosomal recessive type in 29 families, 2 cases of the autosomal dominant type in 6 families, and 74 sporadic cases. Recent reports came from Herold et al. [19881and Roberts et al. 119881. The term spondylocostal dysostosis, used by the “International Nomenclature of Constitutional Diseases of Bone,” was inaugurated by Franceschini et al. [19741. The clinical manifestations allow differentiation between a severe and a mild form. Patients affected by the severe form seldom survive early infancy due to pulmonary complications. This form is presumed to be transmitted exclusively in a n autosomal recessive manner. Evaluation of family histories of patients affected by the mild form shows an autosomal dominant or autosomal recessive mode of inheritance. We report on a father and daughter with SCD. CLINICAL REPORT Patient 1 She was the first child of nonconsanguineous parents who was born a t term through cesarean section after a n uneventful pregnancy. Birth weight was 3,120 g. Respiratory distress called for the immediate transfer of the patient to a neonatal ICU. Under CPAP (continuous positive airway pressure) the symptoms abated within 24 hours. However, the child had to be tube-fed for 10 weeks because of respiratory distress. Neonatally the child was noted to have a short thorax and protruding abdomen (Fig. 1). Radiography showed segmentation defects of thoracic and lumbar vertebrae (predominantly cleft and hemivertebrae). The right hemithorax showed narrowing of the posterior intercostal spaces, with the ribs diverging from back to front like the spokes of a wheel. Additionally there were anomalies of the left upper ribs (Fig. 2). Patient 2 The father of the proposita was the 6th child of nonconsanguineous, healthy parents. Pregnancy and labor were uneventful. The third child of the family died unexpectedly at age 3 years. The fourth child had a congenital heart defect and died a t age 6 months. The patient has been under constant orthopedic supervision for his short thorax with minimal functional impairment. The diagnosis then made was “congenital
220
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kyphoskoliosis” (Figs. 3, 4).Earlier radiographs were not available. Radiographs show scoliosis with the convexity to the left and to the right. Several vertebrae of the lower part of the cervical spine, the thoracic spine, and the lumbosacral region show a sagittal cleft. Wedge-shaped and hemivertebrae are also present. The number of ribs is reduced on both sides. Defective position and several synostoses of the ribs, primarily in the neighbourhood of the costovertebral joints, are seen (Figs. 5 , 6).
Fig. 2. Chest radiograph of patient 1.
DISCUSSION SCD can be subsumed into the etiologically heterogeneous group of segmentation defects ofthe axial skeleton (dyssegmental dysplasia, COVESDEM syndrome, Klippel-Feil anomaly, myelomeningocele with vertebral segmentation defects, oculo-auriculo-vertebral dysplasia). However, malformations of ribs and vertebrae may occur as facultative components of several syndromes (campomelic syndrome, cerebro-costo-mandibular syndrome, asphyxiating thoracic dysplasia, MURCS association, VACTERL association). Differential diagnosis between these conditions, although sometimes rather difficult, is of paramount importance for genetic counselling. In SCD there is a n autosomal dominant and a n autosomal recessive type. Nosology is difficult in sporadic patients. Several attempts have been made t o distinguish between the 2 types on the basis of the clinical manifestations [Casamassima et al., 1981; Devos et al., 1978; Solomon et al., 19781. The severity of the thoracic deformity and the potentially fatal respiratory problems were used as a nosologic criterion. For instance, Solomon et al. 119781classified patients with a “fan-like”thorax under the autosomal recessive type, 15 of 18 patients he included in this group had already died by 18 months. Ayme and Preus U9861 subjected 39 previously re-
Figs. 3, 4.Patient 2 at age 28 years.
Figs. 5, 6. Patient 2: radiographs of the spine.
Fig. 1. Patient 1 at age 7 days.
Dominant Spondylocostal Dysostosis
ported patients to a cluster analysis. They did not succeed in establishing a correlation between the mild form of the disorder and a definite mode of inheritance. The proposita in our case shows severe rib anomalies and a unilateral “fan-like’’ thorax, which Solomon et al. 119781 described in patients with the autosomal recessive form. In this respect, the signs of the family described here differ, at least in the proposita’s case, from those published in the literature, which are certainly associated with the autosomal dominant type. So far, 6 cases have been reported, which by analysis of the respective pedigrees must be assumed to be of the autosoma1 dominant type. Rimoin et al. [19681reported on a boy and his father with disproportionate shortness. Both had a short thorax, while the neck was normal. The mobility of the spine was severely restricted. Radiograph showed malformations of the thoracic and lumbar vertebrae only; the ribs were in part hypoplastic and synostotic. The paternal grandmother and her father, who unfortunately could not be re-examined, were reported to have been affected as well. Riitt and Degenhardt [1959] report on a family in which the mother and 3 of her 4 children were affected. The youngest of the affected children had a different father. Here again, mainly thoracic and lumbar vertebrae were involved. Comparable malformations were found by Kubryk and Borde [19811in a woman and her 2 sons. Peralta et al. [1967] report on a family in which the propositus, father, grandfather, and uncle are affected. The propositus had respiratory problems when eating during early infancy, while the other persons were almost asymptomatic. In this case, cervical, thoracic, and lumbar vertebrae were malformed. There were only slight deformities of the ribs. The symptoms of the 2 patients (mother and daughter)described by van der Sar [1951] were relatively severe. However, they do not include malformations of the ribs a s are found in severe cases of SCD. Another family was described by Waaler and Aarskog [1980]. In this case, 2 of the 4 affected persons (mother and her 3 children) had mild hydrocephalus. The mental development of these patients was normal without any treatment for hydrocephalus. Unyortunately, no radiographs were included in this publication. Thus, in autosomal dominant cases malformations affect mainly the vertebral bodies. These malformations are in part extremely severe and may cause considerable shortness of the thorax,
221
Malformations of the ribs as severe as in our proposita have not been reported in any of these patients. This questions the statement that rib defects resulting in a “fan-like’’ appearance of the thorax are exclusively seen in the autosomal recessive type of SCD. Therefore, it must be concluded that i t is impossible to differentiate between the 2 genetic types of SCD on the basis of the clinical manifestations. The variable severity of the costovertebral malformations in both types of SCD seems to be due to additional factors. This is supported by the simultaneous occurrence of the mild and severe clinical form in same families afflicted with doubtlessly autosomal recessive or autosomal dominant SCD.
REFERENCES Ayme S, Preus M (1986): Spondylocostalispondylothoracicdysostosis: The clinical basis for prognosticating and genetic counseling. Am J Med Genet 24:599-606. Bar P (1903):Nouveau-ne presentant une singuliere malformation de la colonne vertebrale (telescopage vertebral). Sac Obstet Paris 19 novembre 1903. Casamassima AC, Morton CC, Nance WE, KodroffM, Caldwell R, Kelly T, Wolf B (1981): Spondylocostal dysostosis associated with anal and urogenital anomalies in a Mennonite sibship. Am J Med Genet 8:117-127. Devos EA, Leroy JG, Braeckman JJ, Bulcke LJV, Langer LO (1978): Spondylocostal dysostosis and urinary tract anomaly: Definition and review of a n entity. Eur J Pediatr 128:7-15. Fkanceschini P, Grassi E, Fabris C, Bogetti G, Randaccio M (1974): The autosomal recessive form of spondylocostal dysostosis. Radiology 1123673-675, Herald HZ, Edlitz M, Baruchin A (1988):Spondylothoracic dysplasiaA Report of Ten Cases with Follow-up. Spine 13:478-481. Kubryk N, Borde M (1981): La dysostose spondylo-costale. Pediatrie 17:137-146. Peralta A, Lopez C, Gracia R, Crespo LM (1967): Polidispondilia familiar. Rev Pediatr Obstet Gynecol [Pediatr] VII:93-96. Rimoin DL, Fletcher BD, McKusick VA 11968):Spondylocostal dysplasia. Am J Med 45:948-953. Roberts AP, Canner AN, Tblmie JL, Connor J M (1988): Spondylothoracic and spondylocostal dysostosis. J Bone Joint Surg LBrl 70:123-126. Riitt A, Degenhardt KH (1959): Beitrag zur Atiologie und Pathogenese van Wirbelsaulenmissbildungen. Arch Orthop Unfallchir 57:lZO-139. Solomon L, Jimenez B, Reiner L (1978): Spondylothoracic dysostosis. Arch Pathol Lab Med 102:201--205. van der Sar A (1951): Hereditary multiple hemivertebrae. Doc Med Geographica Tropica 4:23-29. Waaler PE, Aarskog D (1980): Syndrome of Hydrocephalus, costovertebral dysplasia and Sprengel anomaly with autosomal dominant inheritance. Neuropediatrics 11:291-297.
Brief Clinical Rkport Spondylocostal Dysostosis: Dominant Type Peter Lorenz and Edgar R u p p r e c h t Departments of Clinical Genetics (P.L.) and Pediatrics (E.R.), Medical Academy Dresden T a r 1 Gustau Carus,” Dresden, German Democratic Republic We report on a f a t h e r and daughter who h a v e spondylocostal dysostosis. The girl’s ribs are more severely abnormal than those of the 2 previously reported cases of dominant spondylocostal dysostosis and are rather suggestive of the autosomal recessive type. T h e differential diagnosis of both forms is discussed. KEY
WORDS: polydysspondylia, JarchoLevin syndrome, LavyPalmer-Merrit syndrome, costovertebral dysplasia, spondylothoracal dysplasia, multiple hemivertebrae, spondylocostal dysplasia, oc-
cipito-facial-cervico-thoracoabdomino-digital syndrome, autosomal dominant inheritance, autosomal recessive inheritance
INTRODUCTION Spondylocostal dysostosis (SCD) is characterized by multiple malformations of ribs and vertebrae. Cleft, fused, wedge-shaped, and hemivertebrae may occur. The ribs may vary in number and shape or be synostotic, primarily near the costovertebral joints. These malformations are the result of presumed segmentation defects of the axial skeleton. As there are no defects of the neural tube, a defective anlage of the notochord seems to be the underlying pathogenetic defect. Shortness of neck and thorax and a bulging abdomen are obvious manifestations of the disorder. Kyphoscoliosis is common. A typical shape of the cranium with protruding occiput, a typical physiognomy, muscular hypotonia, and herniation have been described. The first comparable observation originates from Bar Fkceived for publication November 22, 1988; revision received August 8, 1989. Address reprint requests to D.M. Peter Lorenz, Department of Clinical Genetics of the Medical Academy Dresden “Carl Gustav Carus”, Fetscherstr. 74, Dresden, DDR-8019, GDR.
0 1990 Wiley-Liss, Inc.
[19031. About 172 patients have been published under various synonyms, 78 cases of the autosomal recessive type in 29 families, 2 cases of the autosomal dominant type in 6 families, and 74 sporadic cases. Recent reports came from Herold et al. [19881and Roberts et al. 119881. The term spondylocostal dysostosis, used by the “International Nomenclature of Constitutional Diseases of Bone,” was inaugurated by Franceschini et al. [19741. The clinical manifestations allow differentiation between a severe and a mild form. Patients affected by the severe form seldom survive early infancy due to pulmonary complications. This form is presumed to be transmitted exclusively in a n autosomal recessive manner. Evaluation of family histories of patients affected by the mild form shows an autosomal dominant or autosomal recessive mode of inheritance. We report on a father and daughter with SCD. CLINICAL REPORT Patient 1 She was the first child of nonconsanguineous parents who was born a t term through cesarean section after a n uneventful pregnancy. Birth weight was 3,120 g. Respiratory distress called for the immediate transfer of the patient to a neonatal ICU. Under CPAP (continuous positive airway pressure) the symptoms abated within 24 hours. However, the child had to be tube-fed for 10 weeks because of respiratory distress. Neonatally the child was noted to have a short thorax and protruding abdomen (Fig. 1). Radiography showed segmentation defects of thoracic and lumbar vertebrae (predominantly cleft and hemivertebrae). The right hemithorax showed narrowing of the posterior intercostal spaces, with the ribs diverging from back to front like the spokes of a wheel. Additionally there were anomalies of the left upper ribs (Fig. 2). Patient 2 The father of the proposita was the 6th child of nonconsanguineous, healthy parents. Pregnancy and labor were uneventful. The third child of the family died unexpectedly at age 3 years. The fourth child had a congenital heart defect and died a t age 6 months. The patient has been under constant orthopedic supervision for his short thorax with minimal functional impairment. The diagnosis then made was “congenital
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kyphoskoliosis” (Figs. 3, 4).Earlier radiographs were not available. Radiographs show scoliosis with the convexity to the left and to the right. Several vertebrae of the lower part of the cervical spine, the thoracic spine, and the lumbosacral region show a sagittal cleft. Wedge-shaped and hemivertebrae are also present. The number of ribs is reduced on both sides. Defective position and several synostoses of the ribs, primarily in the neighbourhood of the costovertebral joints, are seen (Figs. 5 , 6).
Fig. 2. Chest radiograph of patient 1.
DISCUSSION SCD can be subsumed into the etiologically heterogeneous group of segmentation defects ofthe axial skeleton (dyssegmental dysplasia, COVESDEM syndrome, Klippel-Feil anomaly, myelomeningocele with vertebral segmentation defects, oculo-auriculo-vertebral dysplasia). However, malformations of ribs and vertebrae may occur as facultative components of several syndromes (campomelic syndrome, cerebro-costo-mandibular syndrome, asphyxiating thoracic dysplasia, MURCS association, VACTERL association). Differential diagnosis between these conditions, although sometimes rather difficult, is of paramount importance for genetic counselling. In SCD there is a n autosomal dominant and a n autosomal recessive type. Nosology is difficult in sporadic patients. Several attempts have been made t o distinguish between the 2 types on the basis of the clinical manifestations [Casamassima et al., 1981; Devos et al., 1978; Solomon et al., 19781. The severity of the thoracic deformity and the potentially fatal respiratory problems were used as a nosologic criterion. For instance, Solomon et al. 119781classified patients with a “fan-like”thorax under the autosomal recessive type, 15 of 18 patients he included in this group had already died by 18 months. Ayme and Preus U9861 subjected 39 previously re-
Figs. 3, 4.Patient 2 at age 28 years.
Figs. 5, 6. Patient 2: radiographs of the spine.
Fig. 1. Patient 1 at age 7 days.
Dominant Spondylocostal Dysostosis
ported patients to a cluster analysis. They did not succeed in establishing a correlation between the mild form of the disorder and a definite mode of inheritance. The proposita in our case shows severe rib anomalies and a unilateral “fan-like’’ thorax, which Solomon et al. 119781 described in patients with the autosomal recessive form. In this respect, the signs of the family described here differ, at least in the proposita’s case, from those published in the literature, which are certainly associated with the autosomal dominant type. So far, 6 cases have been reported, which by analysis of the respective pedigrees must be assumed to be of the autosoma1 dominant type. Rimoin et al. [19681reported on a boy and his father with disproportionate shortness. Both had a short thorax, while the neck was normal. The mobility of the spine was severely restricted. Radiograph showed malformations of the thoracic and lumbar vertebrae only; the ribs were in part hypoplastic and synostotic. The paternal grandmother and her father, who unfortunately could not be re-examined, were reported to have been affected as well. Riitt and Degenhardt [1959] report on a family in which the mother and 3 of her 4 children were affected. The youngest of the affected children had a different father. Here again, mainly thoracic and lumbar vertebrae were involved. Comparable malformations were found by Kubryk and Borde [19811in a woman and her 2 sons. Peralta et al. [1967] report on a family in which the propositus, father, grandfather, and uncle are affected. The propositus had respiratory problems when eating during early infancy, while the other persons were almost asymptomatic. In this case, cervical, thoracic, and lumbar vertebrae were malformed. There were only slight deformities of the ribs. The symptoms of the 2 patients (mother and daughter)described by van der Sar [1951] were relatively severe. However, they do not include malformations of the ribs a s are found in severe cases of SCD. Another family was described by Waaler and Aarskog [1980]. In this case, 2 of the 4 affected persons (mother and her 3 children) had mild hydrocephalus. The mental development of these patients was normal without any treatment for hydrocephalus. Unyortunately, no radiographs were included in this publication. Thus, in autosomal dominant cases malformations affect mainly the vertebral bodies. These malformations are in part extremely severe and may cause considerable shortness of the thorax,
221
Malformations of the ribs as severe as in our proposita have not been reported in any of these patients. This questions the statement that rib defects resulting in a “fan-like’’ appearance of the thorax are exclusively seen in the autosomal recessive type of SCD. Therefore, it must be concluded that i t is impossible to differentiate between the 2 genetic types of SCD on the basis of the clinical manifestations. The variable severity of the costovertebral malformations in both types of SCD seems to be due to additional factors. This is supported by the simultaneous occurrence of the mild and severe clinical form in same families afflicted with doubtlessly autosomal recessive or autosomal dominant SCD.
REFERENCES Ayme S, Preus M (1986): Spondylocostalispondylothoracicdysostosis: The clinical basis for prognosticating and genetic counseling. Am J Med Genet 24:599-606. Bar P (1903):Nouveau-ne presentant une singuliere malformation de la colonne vertebrale (telescopage vertebral). Sac Obstet Paris 19 novembre 1903. Casamassima AC, Morton CC, Nance WE, KodroffM, Caldwell R, Kelly T, Wolf B (1981): Spondylocostal dysostosis associated with anal and urogenital anomalies in a Mennonite sibship. Am J Med Genet 8:117-127. Devos EA, Leroy JG, Braeckman JJ, Bulcke LJV, Langer LO (1978): Spondylocostal dysostosis and urinary tract anomaly: Definition and review of a n entity. Eur J Pediatr 128:7-15. Fkanceschini P, Grassi E, Fabris C, Bogetti G, Randaccio M (1974): The autosomal recessive form of spondylocostal dysostosis. Radiology 1123673-675, Herald HZ, Edlitz M, Baruchin A (1988):Spondylothoracic dysplasiaA Report of Ten Cases with Follow-up. Spine 13:478-481. Kubryk N, Borde M (1981): La dysostose spondylo-costale. Pediatrie 17:137-146. Peralta A, Lopez C, Gracia R, Crespo LM (1967): Polidispondilia familiar. Rev Pediatr Obstet Gynecol [Pediatr] VII:93-96. Rimoin DL, Fletcher BD, McKusick VA 11968):Spondylocostal dysplasia. Am J Med 45:948-953. Roberts AP, Canner AN, Tblmie JL, Connor J M (1988): Spondylothoracic and spondylocostal dysostosis. J Bone Joint Surg LBrl 70:123-126. Riitt A, Degenhardt KH (1959): Beitrag zur Atiologie und Pathogenese van Wirbelsaulenmissbildungen. Arch Orthop Unfallchir 57:lZO-139. Solomon L, Jimenez B, Reiner L (1978): Spondylothoracic dysostosis. Arch Pathol Lab Med 102:201--205. van der Sar A (1951): Hereditary multiple hemivertebrae. Doc Med Geographica Tropica 4:23-29. Waaler PE, Aarskog D (1980): Syndrome of Hydrocephalus, costovertebral dysplasia and Sprengel anomaly with autosomal dominant inheritance. Neuropediatrics 11:291-297.
