American Journal of Medical Genetics 39243-246 (1991)
Brief Clinical Report Short Rib Syndrome Beemer-Langer Type With Polydactyly: A Multiple Congenital Anomalies Syndrome S. Samuel Yang, Joel A. Roth, and Leonard 0. Langer, Jr. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Michigan (SSY); Department of Pathology, Overlook Hospital, Summit, New Jersey (JAR); and Department of Radiology, University of Minnesota Hospital, Minneapolis, Minnesota (LOL)
tion and died 19 minutes later. Labor was induced because a sonogram of the mother showed hydramnios and fetal anomalies including a small heart and cerebral anomalies with hydrocephalus. Amniocyte chromosomes were normal (46,XY). The clinically normal mother was 33 years old, gravida 5, para 1,with three previous miscarriages. The father was 34 years old. There was no consanguinity or family history of dwarfism. Postmortem radiographs (Figs. 1-41 showed 1) very short, horizontal ribs with anterior irregularity and KEY WORDS osteochondrodysplasia, sowidening; 2) small, relatively poorly ossified vertebrae nography, bones and, secondary to this, increased intervertebral spaces; 3) high position of thin clavicles due to thoracic lordosis; 4) small scapulae; 5) small ilia, due to short basilar INTRODUCTION portions and small iliac wings; 6 ) short long tubular Short rib syndrome, Beemer-Langer type was origi- bones; 7) bowed radii and ulnae; 8) relatively normally nally reported as a new short rib syndrome [Beemer et tubulated tibiae that were longer than the fibulae; 9) al., 19831.The affected individuals did not have polydac- absence of conspicuous metaphyseal spicules; 10) and tyly. The neonate reported here had postaxial polydac- short tubular bones of hands and feet, with a postaxial tyly. Therefore, we suggest that short rib (polydactyly) left sixth finger. syndrome, Beemer-Langer type, is a more accurate deAt postmortem examination, this fetus (Fig. 5) was scriptive name, using the established nomenclature for hydropic, weighed 2,440 g, and measured 41 cm crownthis group of conditions. Six patients with this condition to-heel. The head was large with hypertelorism, low have been described. Since pathological examination of nasal bridge, malformed right ear, cleft upper lip and the skeletal system is helpful in distinguishing the dif- palate, and two small nodules of heterotopic cartilage in ferent short rib polydactyly syndromes [Yang et al., the tongue. The neck was short and the chest narrow 19871 and only brief descriptions of the cartilage histo- with wide set nipples. The abdomen was protuberant pathology in SR(P)S, Beemer-Langer type have been and the genitalia ambiguous with absence of the penis. published [Yang et al., 1987; Beemer, 1987; Garcia et Autopsy disclosed a large ductus arteriosus, preductal al., 1988; Chen et al., 19891, we wish to report the post- coarctation of the aorta, malrotation of the intestines, mortem pathologic findings with emphasis on the skele- hypertrophy of the verumontanum, dilatation of the urital system of this patient, which is the first documented nary bladder, mild right hydroureter and hydroexample of this entity with polydactyly. nephrosis, atresia of the left ureteropelvic junction with mild left hydronephrosis, undescended testes in the inCLINICAL REPORT guinal canals, hydrocephalus with single ventricle (hoThis premature male fetus with disproportionate loprosencephaly), agenesis of corpus callosum, a Dandyshortness of the limbs was delivered a t 30 weeks’ gesta- Walker “cerebellar cyst,” and arachnoid cysts of occipital lobes. Received for publication January 2, 1990; revision received AuHistopathologic examination of the skeletal system gust 3, 1990. showed the resting cartilage to be unremarkable. The Address reprint requests t o S. Samuel Yang, M.D., Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, physeal growth zone was disorganized, and there was MI 48072. irregular vascular penetration of the cartilage a t the
A male fetus with short rib (polydactyly) syndrome, Beemer-Langer type was aborted at 30 weeks’ gestation because of abnormalities visualized on sonography. This is the first documented case with polydactyly in this recently defined entity. The clinical, radiological, and pathological findings, especially of the bones, are described. The differential diagnosis of this entity is discussed.
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Fig. 3. Postmortem radiograph, left lower limb of the fetus.
Fig. 1. Postmortem AP radiograph of the fetus
Fig. 4. Postmortem radiograph of the vertebral bodies, upper and lower limbs.
Fig. 2. Postmortem radiograph, left upper limb of the fetus.
metaphyseal border. Moreover, the zone of hypertrophy appeared prominent due to closely arranged large chondrocytic lacunae (Fig. 6). This prominent zone of hypertrophy was demonstrated in proximal humerus, radius, femur, tibia, and distal femur. The same zone was disor-
ganized but not prominent in the vertebra, distal humerus, and radius. Isolated large irregular islands of cartilage were present in the metaphyses of proximal humerus and femur. The cartilage of vertebral bodies had prominently serrated cartilage bone junction with widened zones of provisional calcification (Fig. 7).
DISCUSSION The term Beemer short rib syndrome was first suggested for this condition by Yang et al. 119871. The diag-
Short Rib Syndrome
245
Fig. 5. Postmortem photograph of the fetus. Postaxial polydactyly of left hand is discernible.
Fig. 7. Photomicrograph of the vertebral body with irregular cartilage-bonejunction. The physeal zone of hypertrophy is not prominent. Hematoxylin and eosin, x 54.
Fig. 6. Photomicrograph of the physis with prominent, but disorganized zone of hypertrophy. Hematoxylin and eosin, x 54.
nostic radiographic criteria are as outlined in the current case report except that no polydactyly has been reported in previous patients. The occurrence ofpolydactyly in this patient demonstrates that the condition is actually a short rib (polydactyly) syndrome (SR(P)S) similar to the Saldino-Noonan and Verma-Naumoff types. Polydactyly seems to be rare in the condition being discussed; it is common in the Saldino-Noonan and Verma-Naumofftypes. We suggest the use of parentheses around the word polydactyly to indicate that this is an inconstant feature in these three types. In short rib polydactyly syndrome (SRPS) Majewski type, polydactyly has been a constant feature to date; therefore, no parentheses are used. The eponymic nomenclature of SR(P)SBeemer-Langer type is preferred in this article since Dr. Langer, a co-author of the original article, was instrumental in recognizing and delineating this condition as an entity [Beemer et al., 19831. Six patients with the characteristic radiographic combination of skeletal abnormalities of the Beemer-Langer type have been documented [Beemer et al., 1983 (2 cases); Wladimiroff et a]., 1981 (1 case); Garcia et al., 1988 (1case); Winter, 1988 (1case); Chen et al., 1989 (1
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case)]. Garcia et al. Ll9881 considered their patient a n example of Majewski syndrome, but the clinical and radiographic findings are those of the Beemer-Langer type. The illustrations included in the letter to the editor by Passarge [1983] about two sibs with a short rib syndrome without polydactyly shows broader iliac bones than those of any of the other patients, and i t is doubtful that these sibs had the Beemer-Langer type. It is impossible from the information available to be certain whether Benalkgue et al.’s [1987] patient with cloverleaf skull had the same condition as Passarge’s patients, the Beemer-Langer type, or asphyxiating thoracic dysplasia type 2 (Jeune). It is probable that SR(P)SBeemer-Langer type is a n autosomal recessive condition as the parents of one of the original cases were consanguineous and a subsequent sib was similarly affected [Beemer et al., 19831. The other short rib polydactyly syndromes have been demonstrated to be autosomal recessive conditions. SR(P)S Beemer-Langer type is characterized clinically by median cleft lip,’ small chest with extremely short ribs, protuberant abdomen with umbilical hernia, and ambiguous genitalia in some affected 46,XY individuals. The radiographic skeletal findings are similar to those of SRPS Majewski type in that metaphyseal bone spicules are either not present or very inconspicuous in these two conditions. Prominent spicules are present in SR(P)S Saldino-Noonan type and in SR(P)S VermaNaumoff type. The differences between the Majewski type and the Beemer-Langer type include undertubulated tibiae which are shorter than the fibulae in the Majewski type in contrast t o more normally modeled tibiae, which are longer than the fibulae in the BeemerLanger type. There is definite bowing of the ulna and radius in the Beemer-Langer type, with minimal or no bowing in the Majewski type. The ilia are small, both the basilar portions and iliac wings, in the BeemerLanger type while the pelvis in the Majewski type is normal. Preaxial and/or postaxial polydactyly is present in the Majewski type, but documented polydactyly, which was postaxial, has been present in the BeemerLanger type only in the patient reported in this article. The patient with this condition and polydactyly mentioned by Spranger [Beemer, 19871 was probably our patient, whose radiographs were seen by him in consultation before this new entity was established. Chondroectodermal dysplasia (Ellis-van Creveld) and asphyxiating thoracic dysplasia type 2 (Jeune) [Yang et al., 19871 are not usually differential diagnostic possibilities because of the longer ribs in those conditions
‘Absent in Chen e t al.’s 119891 patient.
than in the Beemer-Langer type. There are similarities in the limb and iliac bones in these three conditions. The histopathologic findings of a prominent but disorganized physeal hypertrophic zone in the Beemer-Langer type described in this article appears distinct when compared to the other types of short rib polydactyly syndromes and are compatible with two earlier, very brief pathologic descriptions of this entity [Yang et al., 1987; Beemer, 19871.However, the histopathologic findings of the cartilage reported by Garcia et al. [19881 and by Chen et al. [1989] demonstrated only a disorganized physeal growth plate without significant chondrocytic hypertrophy. Additional cases are needed to clarify whether the discrepancy is due to heterogeneity of the cases or to variability of cartilage histopathology in different anatomic sites. Similar pathologic changes were observed in the ribs and vertebral bodies of a patient who had the histologic changes of asphyxiating thoracic dysplasia type 2 (Jeune) in the femoral heads and who fit this latter diagnosis by radiographic criteria [Yang et al., 19871. We think the clinical and radiological findings allow separation of the Langer-Beemer type from the other types of short rib polydactyly syndromes. More cases with more anatomic sites evaluated should clarify the role of histopathology in the diagnosis of this entity.
ACKNOWLEDGMENTS The authors gratefully acknowledge the assistance of Alexander Cacciarelli, M.D., Pediatric Radiology, Department of Diagnostic Radiology, and the review of the manuscript by Jay Bernstein, M.D., Research Institute, William Beaumont Hospital, Royal Oak, Michigan. REFERENCES Beemer FA (1987):Short rib syndrome classification.Am J Med Genet [Suppll 3:209-210. Beemer FA, Langer LO, Jr., Klep-de Pater JM, Hemmes AM, Bylsma JB, Pauli RM, Myers TL, Haws CC, I11 (1983): A New Short Rib Syndrome: Report of two cases. Am J Med Genet 14:115-123. Benallegue A, Lacete F, Maroteaux P (1987):Crdne en trefle associe a une atteinte generalisee du squelette proche de a dysplasie thoracique asphyxiante. Ann Genet 30:113-117. Chen K, McKeever PA, Young ID (1989): Short rib syndrome without polydactyly. J Med Genet 26:346-347. Garcia H, Drescher H, Kochelmeister K, Lenz W, Roessner A (1988): Short rib polydactyly syndromes. Klin Padiatr 200:140-144. Passarge E (1983): Familial occurrence of a short rib syndrome with hydrops fetalis but without polydactyly. Am J Med Genet 14:403405. Yang SS, Langer LO Jr, Cacciarelli A, Dahms BB. Unger ER, Roskamp J , Dinno ND, Chen H (1987):Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib polydactyly syndrome spectrum: A clinicopathologic study. Am J Med Genet [Suppl] 3:191-207. Winter R (1988): A lethal short rib syndrome without polydactyly. J Med Genet 25:349-351. Wladimiroff JW, Beemer FA, Hemmes AM (1981):Early diagnosis of skeletal dysplasia by real-time ultrasound. Lancet 1:661-662.
Brief Clinical Report Short Rib Syndrome Beemer-Langer Type With Polydactyly: A Multiple Congenital Anomalies Syndrome S. Samuel Yang, Joel A. Roth, and Leonard 0. Langer, Jr. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Michigan (SSY); Department of Pathology, Overlook Hospital, Summit, New Jersey (JAR); and Department of Radiology, University of Minnesota Hospital, Minneapolis, Minnesota (LOL)
tion and died 19 minutes later. Labor was induced because a sonogram of the mother showed hydramnios and fetal anomalies including a small heart and cerebral anomalies with hydrocephalus. Amniocyte chromosomes were normal (46,XY). The clinically normal mother was 33 years old, gravida 5, para 1,with three previous miscarriages. The father was 34 years old. There was no consanguinity or family history of dwarfism. Postmortem radiographs (Figs. 1-41 showed 1) very short, horizontal ribs with anterior irregularity and KEY WORDS osteochondrodysplasia, sowidening; 2) small, relatively poorly ossified vertebrae nography, bones and, secondary to this, increased intervertebral spaces; 3) high position of thin clavicles due to thoracic lordosis; 4) small scapulae; 5) small ilia, due to short basilar INTRODUCTION portions and small iliac wings; 6 ) short long tubular Short rib syndrome, Beemer-Langer type was origi- bones; 7) bowed radii and ulnae; 8) relatively normally nally reported as a new short rib syndrome [Beemer et tubulated tibiae that were longer than the fibulae; 9) al., 19831.The affected individuals did not have polydac- absence of conspicuous metaphyseal spicules; 10) and tyly. The neonate reported here had postaxial polydac- short tubular bones of hands and feet, with a postaxial tyly. Therefore, we suggest that short rib (polydactyly) left sixth finger. syndrome, Beemer-Langer type, is a more accurate deAt postmortem examination, this fetus (Fig. 5) was scriptive name, using the established nomenclature for hydropic, weighed 2,440 g, and measured 41 cm crownthis group of conditions. Six patients with this condition to-heel. The head was large with hypertelorism, low have been described. Since pathological examination of nasal bridge, malformed right ear, cleft upper lip and the skeletal system is helpful in distinguishing the dif- palate, and two small nodules of heterotopic cartilage in ferent short rib polydactyly syndromes [Yang et al., the tongue. The neck was short and the chest narrow 19871 and only brief descriptions of the cartilage histo- with wide set nipples. The abdomen was protuberant pathology in SR(P)S, Beemer-Langer type have been and the genitalia ambiguous with absence of the penis. published [Yang et al., 1987; Beemer, 1987; Garcia et Autopsy disclosed a large ductus arteriosus, preductal al., 1988; Chen et al., 19891, we wish to report the post- coarctation of the aorta, malrotation of the intestines, mortem pathologic findings with emphasis on the skele- hypertrophy of the verumontanum, dilatation of the urital system of this patient, which is the first documented nary bladder, mild right hydroureter and hydroexample of this entity with polydactyly. nephrosis, atresia of the left ureteropelvic junction with mild left hydronephrosis, undescended testes in the inCLINICAL REPORT guinal canals, hydrocephalus with single ventricle (hoThis premature male fetus with disproportionate loprosencephaly), agenesis of corpus callosum, a Dandyshortness of the limbs was delivered a t 30 weeks’ gesta- Walker “cerebellar cyst,” and arachnoid cysts of occipital lobes. Received for publication January 2, 1990; revision received AuHistopathologic examination of the skeletal system gust 3, 1990. showed the resting cartilage to be unremarkable. The Address reprint requests t o S. Samuel Yang, M.D., Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, physeal growth zone was disorganized, and there was MI 48072. irregular vascular penetration of the cartilage a t the
A male fetus with short rib (polydactyly) syndrome, Beemer-Langer type was aborted at 30 weeks’ gestation because of abnormalities visualized on sonography. This is the first documented case with polydactyly in this recently defined entity. The clinical, radiological, and pathological findings, especially of the bones, are described. The differential diagnosis of this entity is discussed.
0 1991 Wiley-Liss, Inc.
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Fig. 3. Postmortem radiograph, left lower limb of the fetus.
Fig. 1. Postmortem AP radiograph of the fetus
Fig. 4. Postmortem radiograph of the vertebral bodies, upper and lower limbs.
Fig. 2. Postmortem radiograph, left upper limb of the fetus.
metaphyseal border. Moreover, the zone of hypertrophy appeared prominent due to closely arranged large chondrocytic lacunae (Fig. 6). This prominent zone of hypertrophy was demonstrated in proximal humerus, radius, femur, tibia, and distal femur. The same zone was disor-
ganized but not prominent in the vertebra, distal humerus, and radius. Isolated large irregular islands of cartilage were present in the metaphyses of proximal humerus and femur. The cartilage of vertebral bodies had prominently serrated cartilage bone junction with widened zones of provisional calcification (Fig. 7).
DISCUSSION The term Beemer short rib syndrome was first suggested for this condition by Yang et al. 119871. The diag-
Short Rib Syndrome
245
Fig. 5. Postmortem photograph of the fetus. Postaxial polydactyly of left hand is discernible.
Fig. 7. Photomicrograph of the vertebral body with irregular cartilage-bonejunction. The physeal zone of hypertrophy is not prominent. Hematoxylin and eosin, x 54.
Fig. 6. Photomicrograph of the physis with prominent, but disorganized zone of hypertrophy. Hematoxylin and eosin, x 54.
nostic radiographic criteria are as outlined in the current case report except that no polydactyly has been reported in previous patients. The occurrence ofpolydactyly in this patient demonstrates that the condition is actually a short rib (polydactyly) syndrome (SR(P)S) similar to the Saldino-Noonan and Verma-Naumoff types. Polydactyly seems to be rare in the condition being discussed; it is common in the Saldino-Noonan and Verma-Naumofftypes. We suggest the use of parentheses around the word polydactyly to indicate that this is an inconstant feature in these three types. In short rib polydactyly syndrome (SRPS) Majewski type, polydactyly has been a constant feature to date; therefore, no parentheses are used. The eponymic nomenclature of SR(P)SBeemer-Langer type is preferred in this article since Dr. Langer, a co-author of the original article, was instrumental in recognizing and delineating this condition as an entity [Beemer et al., 19831. Six patients with the characteristic radiographic combination of skeletal abnormalities of the Beemer-Langer type have been documented [Beemer et al., 1983 (2 cases); Wladimiroff et a]., 1981 (1 case); Garcia et al., 1988 (1case); Winter, 1988 (1case); Chen et al., 1989 (1
246
Yang et al.
case)]. Garcia et al. Ll9881 considered their patient a n example of Majewski syndrome, but the clinical and radiographic findings are those of the Beemer-Langer type. The illustrations included in the letter to the editor by Passarge [1983] about two sibs with a short rib syndrome without polydactyly shows broader iliac bones than those of any of the other patients, and i t is doubtful that these sibs had the Beemer-Langer type. It is impossible from the information available to be certain whether Benalkgue et al.’s [1987] patient with cloverleaf skull had the same condition as Passarge’s patients, the Beemer-Langer type, or asphyxiating thoracic dysplasia type 2 (Jeune). It is probable that SR(P)SBeemer-Langer type is a n autosomal recessive condition as the parents of one of the original cases were consanguineous and a subsequent sib was similarly affected [Beemer et al., 19831. The other short rib polydactyly syndromes have been demonstrated to be autosomal recessive conditions. SR(P)S Beemer-Langer type is characterized clinically by median cleft lip,’ small chest with extremely short ribs, protuberant abdomen with umbilical hernia, and ambiguous genitalia in some affected 46,XY individuals. The radiographic skeletal findings are similar to those of SRPS Majewski type in that metaphyseal bone spicules are either not present or very inconspicuous in these two conditions. Prominent spicules are present in SR(P)S Saldino-Noonan type and in SR(P)S VermaNaumoff type. The differences between the Majewski type and the Beemer-Langer type include undertubulated tibiae which are shorter than the fibulae in the Majewski type in contrast t o more normally modeled tibiae, which are longer than the fibulae in the BeemerLanger type. There is definite bowing of the ulna and radius in the Beemer-Langer type, with minimal or no bowing in the Majewski type. The ilia are small, both the basilar portions and iliac wings, in the BeemerLanger type while the pelvis in the Majewski type is normal. Preaxial and/or postaxial polydactyly is present in the Majewski type, but documented polydactyly, which was postaxial, has been present in the BeemerLanger type only in the patient reported in this article. The patient with this condition and polydactyly mentioned by Spranger [Beemer, 19871 was probably our patient, whose radiographs were seen by him in consultation before this new entity was established. Chondroectodermal dysplasia (Ellis-van Creveld) and asphyxiating thoracic dysplasia type 2 (Jeune) [Yang et al., 19871 are not usually differential diagnostic possibilities because of the longer ribs in those conditions
‘Absent in Chen e t al.’s 119891 patient.
than in the Beemer-Langer type. There are similarities in the limb and iliac bones in these three conditions. The histopathologic findings of a prominent but disorganized physeal hypertrophic zone in the Beemer-Langer type described in this article appears distinct when compared to the other types of short rib polydactyly syndromes and are compatible with two earlier, very brief pathologic descriptions of this entity [Yang et al., 1987; Beemer, 19871.However, the histopathologic findings of the cartilage reported by Garcia et al. [19881 and by Chen et al. [1989] demonstrated only a disorganized physeal growth plate without significant chondrocytic hypertrophy. Additional cases are needed to clarify whether the discrepancy is due to heterogeneity of the cases or to variability of cartilage histopathology in different anatomic sites. Similar pathologic changes were observed in the ribs and vertebral bodies of a patient who had the histologic changes of asphyxiating thoracic dysplasia type 2 (Jeune) in the femoral heads and who fit this latter diagnosis by radiographic criteria [Yang et al., 19871. We think the clinical and radiological findings allow separation of the Langer-Beemer type from the other types of short rib polydactyly syndromes. More cases with more anatomic sites evaluated should clarify the role of histopathology in the diagnosis of this entity.
ACKNOWLEDGMENTS The authors gratefully acknowledge the assistance of Alexander Cacciarelli, M.D., Pediatric Radiology, Department of Diagnostic Radiology, and the review of the manuscript by Jay Bernstein, M.D., Research Institute, William Beaumont Hospital, Royal Oak, Michigan. REFERENCES Beemer FA (1987):Short rib syndrome classification.Am J Med Genet [Suppll 3:209-210. Beemer FA, Langer LO, Jr., Klep-de Pater JM, Hemmes AM, Bylsma JB, Pauli RM, Myers TL, Haws CC, I11 (1983): A New Short Rib Syndrome: Report of two cases. Am J Med Genet 14:115-123. Benallegue A, Lacete F, Maroteaux P (1987):Crdne en trefle associe a une atteinte generalisee du squelette proche de a dysplasie thoracique asphyxiante. Ann Genet 30:113-117. Chen K, McKeever PA, Young ID (1989): Short rib syndrome without polydactyly. J Med Genet 26:346-347. Garcia H, Drescher H, Kochelmeister K, Lenz W, Roessner A (1988): Short rib polydactyly syndromes. Klin Padiatr 200:140-144. Passarge E (1983): Familial occurrence of a short rib syndrome with hydrops fetalis but without polydactyly. Am J Med Genet 14:403405. Yang SS, Langer LO Jr, Cacciarelli A, Dahms BB. Unger ER, Roskamp J , Dinno ND, Chen H (1987):Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib polydactyly syndrome spectrum: A clinicopathologic study. Am J Med Genet [Suppl] 3:191-207. Winter R (1988): A lethal short rib syndrome without polydactyly. J Med Genet 25:349-351. Wladimiroff JW, Beemer FA, Hemmes AM (1981):Early diagnosis of skeletal dysplasia by real-time ultrasound. Lancet 1:661-662.
