American Journal of Medical Genetics 44:31-36 (1992)
Brief Clinical Report
Unusual Short Rib-Polydactyly Syndrome Yung-Chieh Tsai, Jye-Min Chang, Chan-Chao Changchien, Hock-Liew Eng, Wei-Jen Chen, ChunChung Lui, and ChurngBin Huang Department of Obstetrics and Gynecology (Y.C.T., J.M.C., C.C.CC.), Pathology (H.L.E., W.J.C.), Diagnostic Radwlogy (C.C.L.), and Pediatrics (C.B.H.), Chang Gung Memorial Hospital, Kaohsiung, Taiwan, R.O.C. We present a case of lethal short rib-polydactyly syndrome (SRPS) that cannot be categorized into the existing classification. A nosologic discussion is presented. To OUT knowledge, situs inversus totalis, as in our case, has not been described before in any SRPS. O 1992 Wiiey-Lisa, Inc.
KEY WORDS short-rib syndrome, neonatal death, lethal skeletal dysplasia, autosomal recessive inheritance, polydactyly, shortrib polydactyly syndrome INTRODUCTION The short rib-polydactyly syndromes (SRPS) are a group of lethal skeletal dysplasia with an autosomal recessive mode of inheritance. The SRPS have been classified into 3 types: 1.SRPS 1(Saldino-Noonan)[Saldino and Noonan, 1972],2. SRPS 11(Majewski) [Majewski et al., 19711,3. SRPS 111 (Verma-Naumof€J[Verma et al., 1975;Naumoff et al., 19771.The Majewski type of SRPS is characterized by short ribs, short limbs, preaxial and postaxial polydactyly, brachydactyly, syndactyly, cleft lip, cleft palate, and abnormalities of the epiglottis and viscera. Pelvis and vertebrae are grossly normal, but there is a disproportionately short oval-shape tibia [Majewski et al., 1971; Spranger et al., 1974; Motegi et al., 1979; Cooper et al., 1982; Walley et al., 19831. The Saldino-Noonan type of SRPS is characterized by short ribs and limbs, postaxial polydactyly, syndactyly, metaphyseal irregularities of the long bones with spur formation, visceral abnormalities, an abnormal pelvis with hypoplasia of the iliac bones and acetabular flatness, notch-like ossification defects around the periphery of
the vertebral bodies, normal lips, palate, and epiglottis [Saldino and Noonan, 1972; Spranger et al., 19741. SRPS 1 [Saldino-Noonan] and SRPS 111 VermaNaumoff)are thought to be allelic disorders representing variability in expression of the same mutation or different mutations at the same gene locus [Silence, 1980; Bernstein et al., 19851. They have many clinical and radiographic findings in common but can be differentiated by the configuration at the ends of long bones (pointed in type 1 and rounded with lateral spiculation in type 1111, short cranial base, and horizontal tridentshape acetabular margins (type 111) [ Yang et al., 1980, Bemstein et al., 1985;Silence et al., 19871.Beemer et al. [19831 described a new form of short-rib syndrome that shared most of the manifestation of SRPS 11but without polydactyly [Winter, 1988; Chen et al., 1989; van Maldergem et al., 19901. Yang et al. [19871 first suggested the term “Beemer short rib syndrome.” A case of the Beemer short rib syndrome with polydactyly was reported by Yang et al. [1991]. They recommended the eponym “Beemer-Langer” and used the abbreviation SR(P)S to indicate variable polydactyly. Though different subtypes of SRPSwas proposed to clarify this confusing syndrome [Spranger and Maroteaux, 19901, some authors have suggested that the SRPS are a single entity with varying expressivity [Bidot-Lopezet al., 1978; Silence, 1980; Walley et al., 1983; Bernstein et al., 19851. We report on a case that cannot be definitely categorized into the above mentioned forms, yet possesses some of the manifestations of al1 forms. These observations seem to support the contention of a single entity with varying expressivity.
CLINICAL REPORT A 36-year-oldwoman, gravida 3 para 2, a t 32 + weeks of gestation, was noted to carry a fetus with multiple abnormalities including macrocephaly, occipital bone defect, short limbs, and omphalocele by sonographic exReceived for publication July 15, 1991; revision received Janu- amination. The nonconsanguineous couple already had 2 healthy girls, and termination of the pregnancy was ary 22, 1992. requested. Cesarean section was performed due to macAddress reprint requests to Yung-Chieh Tsai, M.D., Department of Obstetrics and Gynecology, Chang Gung Memorial Hospi- roceph a1y. The male baby died immediately after birth. Gross tal, 123,TA Pei Rd., Niao Sung Kaohsiung, Taiwan, R.O.C.
O 1992 Wiley-Liss,
Inc.
32
Tsai et al.
Fig. 1. Postmorkm photograph of the fetus (see text for description).
Fig. 3. Postaxial polysyndactyly (left hand).
postmortem findings included (Figs. 1-4):generalized hydrops fetus with a 3,400gm body weight, 38 cm body length, head circumference 41 cm, chest circumference 39 cm, and an abdominal circumference 42 cm. He also had micromelic dwarfism with flattened face, prominent forehead, ocular hypertelorism, prominent epicanthal folds, small, flat, and apparently low-set hypoplastic ears. The hard palate was intact. There was a deep fissure in the midline of the upper and lower lips; the tongue was normal. The neck was relatively short. Marked edeme was noted over the scalp, face, and neck. The chest was symmetrical but rather small in size. The
Fig. 2. Deep fissure in the upper and lower lips of the fetus.
Fig. 4. Postaxial polysyndactyly of legs.
abdomen was distended and soft. An omphalocele measuring 8 x 6.5 cm with umbilical cord carrying 2 arteries and one vein was noted. The externa1 genitalia were normal. The anus was patent with meconium staining. "he back showed no deformity with the spine palpable in the midline. The limbs were short with post-axial polysyndactyly of al1 limbs (6 fingers on each of the 4 limbs). An encephalocele protruded from the occipital bone. In addition, there were situs inversus totalis with bilateral pulmonary hypoplasia and right renal hydronephrosis. "he other interna1 organs appeared grossly normal. Microscopically, the epiphyseal growth plates from
SRP Syndrome
tubular bone were attenuated with short proliferative cell columns and irregular chondro-osseoustransformation. No PAS-positive intracytoplasmic granules or inclusion bodies were observed. Radiographs of the skeleton (Figs. 5-8) indicated an occipital bone defect with flat basal angle and a rectilinear mandible with an obtuse mandibular angle, short ribs with widening of anterior ends. Small scapulae and short tubular bones with bowing of the radii, ulnae, and femora. Metaphyseal irregularity with spiking was noted in the fibula. Round dista1 ends of the femora and tibiae were noted. The number and configuration of vertebrae were normal, as was the pelvis. Polysyndactyly was present in al1 4 limbs. Chromosomes were apparently normal
(46XY). DISCUSSION The presence of short horizontal ribs, hypoplastic lung, polydactyly severe micromelia, and generalized systemic abnormalities placed this case into the category of SRPS. However, it becomes difficult when one tries to classify it into the specific types of SRPS. Table 1 illustrates the different types in comparison with our case. F’rom this table, it is obvious that SRPS 1and 111 can be ruled out because of the absence of typical metaphyseal irregularity. It is also unlikely that our case is a type 11 SRPS because the ovoid tibiae are absent. Beemer et al. [19831 have described a new form of SRPS that shared most of the manifestations of SRPS 11but without polydactyly. They are characterized clinically by median cleft lip with or without cleft palate, small chest with extremely short ribs, protuberant abdomen with omphalocele, and radiographically by bowing of the radius and ulnar, small ilia, and normal tibiae, which is longer than fibula. A case that mimicked Beemer short rib syndrome but with polydactyly was reported by Yang et al. [19911. They thus proposed that the Beemer short rib syndrome was actually a condition of short rib (polydactyly) syndrome. The abbreviation SR(P)S was used to indicate variable polydactyly and the eponym “Beemer-Langer” was recommended. Comparison of our case with some of Beemer-Langer type of SR(P)S [Beemer et al., 1983; Winter, 1988; van Maldergem et al., 1990; Lin et al., 1991; Yang et al., 19911 is tabulated in Table 11. Though our case has many common findings with the BeemerLanger type of SR(P)S,the characteristic cleft lip with or without cleft palate is absent. Besides, the histopathologic findings of attenuated epiphyseal proliferative zone with irregular chondro-osseous transformation in our case are also different from published cartilage histopathology of the Beemer-Langer type of SR(P)S [Beemer, 1987; Chen et al., 1989; Yang et al., 1987; Garcia et al., 1989; Lin et al., 1991; Yang et al., 19911. Spranger and Maroteaux [1990] proposed that there were at least 7 types of SRPS, which included type 1 (Saldino-Noonan),type 11(Verma-Naumoff),type 111(Le Marec), type IV (Yang),type V (Jeune),type VI (Majewski), type VI1 (Beemer). In their new classification, type 111 (Le Marec), IV (Yang), and V (Jeune) are new subtypes. Type 111 (LeMarec) of SRPS basically resembles
Fig. 5. Postmortem AP radiograph of the fetus.
Fig. 6. Occipital bone defect with flat basal angle.
33
34
Tsai et al.
Fig. 7. Bowing of the radii and ulnae.
Fig. 8. Lateral speculation of the fibula.
Saldino-Noonon and Verma-Naumoff types of SRPS, but the ribs are not as short as in SRP 1 and 111 and the femora are relatively well formed with round proximal ends. m e IV SRPS (Yang) is characterized by peculiar deformity of the ulna and less markedly of the radius, cleft lip/palate, and cytoplasmic inclusions in chondrocytes of the resting cartilage. Asphyxiating thoracic dysplasia, which has much longer ribs than other SRPS, is considered as type V (Jeune) in their report. The
different findings between their types 111,IV, and IV and our case are apparent, and obviously this case cannot be categorized into any of them. Kozlowski et al. [19771 reported on a case with many findings similar to SRPS type 11but without ovoid tibia and cleft lip/palate. It was later regarded as an atypical form of SRP 11by Cherstvoy et al. [19801. Our case had many similar abnormalities as his. Wider variations, such as bilateral lateral spur formation of the fibulae,
SRP Syndrome
35
TABLE 1. Distinctive Manifestations of Different m e s of SRPS and the Findings in This Case m e1 (Saldinop p e 11 Noonon) (Majewski)
Distinctive trait Externa1 appearance Polydactyly Syndact yly Flat face Flat occiput Cleft liplpalate Rudimentary epiglottis Hydrops Radiological abnormalities Metaphyseal dysplasia Pointed Round with lateral spiculation Ovoid tibia Pelvic abnormalities Vertebral abnormalities Short cranial base Triangular ossification defect (lat. aspect of acetabulum)
+ + + + -1-
+ +-
+ + +
+-
+
+/+
+ +
+
-
+
This case
+
+ -
' s p e 111 (VermaNaumoM
-
-
+
-
-
+ + + +
++/-
-
+
-
+-
encephalocele deep fissure
-1-
minimal -
-
+-
+
TABLE 11. Comparison of the SR(P)SBeemer-Langer Type with This case Beemer (1) (2) Macrocephaly Flat face Cleft liplpalate Ascites Omphalocele Short ribs Small scapulae Short tubular bone Metaphyseal irregularity Bowing of radiitulnae Bowing of femora Polydactyly Familv historv
+
+ +/+ + + + + ++
minimal -
consancr
+ + +/+ + + + ++
min im a1 -
Winter
Maldergem
Lin
Yang
+
+ + +/+ + + + + + minimal +-
+
+
+
+/+
+ + + + + min im a 1 + -
+
+
+ + + + +-
+ + + + + + +
+la +/+
-
-
-
-
+
This Case
+
+ deep fissure + + + +
-
+ +
min im a1 min im a1
+ -
"Grooved palate.
bowed radii and ulnae, omphalocele, encephalocele, and complete situs inversus, were also present. Whether our case should be considered as an atypical form of SRP 11 or another variation of Beemer-Langer type of SR(P)S remains to be determined. According to Bernstein's view, SRPS is a single syndrome with a wide spectrum of anatomical abnormalities. The skeletal manifestations are the most dramatic finding and the generalized systemic abnormalities of al1 organ systems seem to suggest a defect in regulation of cellular differentiation during early embryogenesis [Bernstein et al., 19851. The findings in our case consisting of parts of al1 known SRPS types further support this contention.
ACKNOWLEDGMENTS We gratefully acknowledge the assistance and the review of the manuscript by Dr. John M. Opitz, Department of Medical Genetics, Shodair Children's Hospital, Helena, MT. We also thank Miss Chyung-Mei Yeh for typing this manuscript.
REFERENCES Beemer FA (1987):Short rib syndrome classification. Am J Med Genet [Suppl] 3:209-210. Beemer FA, Langer LO Jr, Klep-de Pater JM, Hemmes AM, Bylsma JB, Pauli RM, Myers TL, Haws 111CC (1983): Anew short rib syndrome: Report of two cases. Am J Med Genet 14:115-123. Bernstein R, Isdaie J , Pinto M, Du Toit Zaaijman J, Jenkins T (1985): Short rib-polydactyly syndrome: a single or heterogenous entity? A re-evaluation prompted by four cases. J Med Genet 2246-53. Bidot-Lopez P, Ablow RC, Ogden JA, Mahoney MJ (1978): A Case of Short Rib Polydactyly. Pediatrics 61(3):427-432. Cherstvoy ED, Lurie IW, Shved iA,Lazjuk GI, Ostrowskaya TI, Usoev SS (1980): Diffculties in classification of the short rib-polydactyly syndrome. Eur J Pediatr 133(1):57-61. Chen K, Mckeever PA, Young ID (1989): Short rib syndrome without polydactyly. J Med Genet 26346-347. Cooper CP, Hall CM (1982): Lethal Short-Rib Polydactyly Syndrome of the Majewski Type: A Report of Three Case. Ped Radio1 144:513517. Garcia H, Drescher H, Kuchelmeister K, Lenz W, Roessner A (1988): Short rib-polydactyly syndromes. Klin Padiatr 200(2):140-144.
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Kozlowski K, Masel J, Morris L, Ryan J , Collins E, Van Vliet P, Woolnough H (1977):Neonatal Death Dwarfkm (Report of 17 cases). Aust Radiol 21:164-183. Lin AE, Doshi N, Flom L, Tenenholz B, Filkins KL (1991):BeemerLanger Syndrome With Manifestations of a n Orofaciodigital syn&me. Am J Med Genit 39(3):247-251. Majewski F, Pfeiffer RA, Lenz W, Muller R, Feil G, Seiler R (1971): Polysyndactyly, short limbs, and genital rnalformations-a new syndrome? Z Kinderheilkd 111(2):118-138. Motegi T, Kusunoki M, Nishi T,Hamada T, Sato N, Irnamura T,Mohri N (1979):Short Rib-Polydactyly Syndrome, Majewski Type, in Two Male siblings. Hum Genet 49:269-275. Naumoff P, Young LW, Mazer J , Amortequi AJ (1977):Short rib polydactyly Syndrome Type 3.Ped Radiol 122:443-447. Saldino RM, Noonan CD (1972):Severe thoracic dystrophy with striking micromelia, abnormal osseous development, including the spine, and multiple visceral anomalies. Arn J Roentgenol 114(3):257-263. Silence D, Kozlowski K, Bar-Ziv J, Fiihrurnann-Rieger A, Fuhrmann W, Pascu F (1987):Perinatally lethal short rib-polydactyly syndromes. 1.Variability in known syndromes. Pediatr Radiol 17:474480. Silence DO (1980):Invited editorial comment Non-Majewski short ribpolydactyly syndrome. Arn J Med Genet 7:223-229. Spranger J, Grirnm B, Weller M, WeiBenbacher G,Hemnann J, Gilbert E,Krepler R (1974):Short Rib-Polydactyly (SRP) syndrome, Types Majewski and Saldino-Noonan. Z Kinderheilk 116(2):73-94.
Spranger J, Maroteaux P (1990):The lethal osteochondrcdysplasias. Advances in Human Genetics 19:l-103. van Maldergern L, Gillerot Y, Salmin E, Verloes A, Koulischer L (1990): Lethal short-rib with median cleft and without polydactyly: a fourth case. Pediatr Radiol 20367-368. Verma IC, Bhargava S,Agarwal S (1975):An autosomal recessive form of lethal chondrodystrophy with severe thoracic narrowing, rhizoacromelic type of rnicrornelia, polydactyly and genital anomalies. Birth defects 11(6):167-174. Walley VM, Coates CF, Gilbert JJ, Valentine GH, Davies EM (1983): Brief Clinical Report: Short Rib-Polydactyly Syndrome, Majewski Type. Am J Med Genet 14:445-452. Winter RM (1988):A lethal short-rib without polydactyly. J Med Genet 25349-357. Yang SS, Langer LO, Cacciarelli A, Dahms BB, Unger ER, Roskarnp J, Dinno ND, Chen H (1987):Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib-polydactyly syndrorne spectrurn: A clinicopathologic study. Am J Med Genet [Suppl] 3:191-207. Yang SS, Lin CS, Al Saadi A, Nangia BS, Bemstein J (1980):Short ribpolydactyly syndrome, type 3 with chondrocyte inclusion: report of a case and review of the literature. Am J Med Genet 7(2):205-213. Yang SS, Roth JA, Langer LO Jr (1991):Short Rib Syndrorne Beemer Langer Type With Polydactyly: A Multiple Congenital Anomalies Syndrome. Arn J Med Genet 39(3): 243-246
Brief Clinical Report
Unusual Short Rib-Polydactyly Syndrome Yung-Chieh Tsai, Jye-Min Chang, Chan-Chao Changchien, Hock-Liew Eng, Wei-Jen Chen, ChunChung Lui, and ChurngBin Huang Department of Obstetrics and Gynecology (Y.C.T., J.M.C., C.C.CC.), Pathology (H.L.E., W.J.C.), Diagnostic Radwlogy (C.C.L.), and Pediatrics (C.B.H.), Chang Gung Memorial Hospital, Kaohsiung, Taiwan, R.O.C. We present a case of lethal short rib-polydactyly syndrome (SRPS) that cannot be categorized into the existing classification. A nosologic discussion is presented. To OUT knowledge, situs inversus totalis, as in our case, has not been described before in any SRPS. O 1992 Wiiey-Lisa, Inc.
KEY WORDS short-rib syndrome, neonatal death, lethal skeletal dysplasia, autosomal recessive inheritance, polydactyly, shortrib polydactyly syndrome INTRODUCTION The short rib-polydactyly syndromes (SRPS) are a group of lethal skeletal dysplasia with an autosomal recessive mode of inheritance. The SRPS have been classified into 3 types: 1.SRPS 1(Saldino-Noonan)[Saldino and Noonan, 1972],2. SRPS 11(Majewski) [Majewski et al., 19711,3. SRPS 111 (Verma-Naumof€J[Verma et al., 1975;Naumoff et al., 19771.The Majewski type of SRPS is characterized by short ribs, short limbs, preaxial and postaxial polydactyly, brachydactyly, syndactyly, cleft lip, cleft palate, and abnormalities of the epiglottis and viscera. Pelvis and vertebrae are grossly normal, but there is a disproportionately short oval-shape tibia [Majewski et al., 1971; Spranger et al., 1974; Motegi et al., 1979; Cooper et al., 1982; Walley et al., 19831. The Saldino-Noonan type of SRPS is characterized by short ribs and limbs, postaxial polydactyly, syndactyly, metaphyseal irregularities of the long bones with spur formation, visceral abnormalities, an abnormal pelvis with hypoplasia of the iliac bones and acetabular flatness, notch-like ossification defects around the periphery of
the vertebral bodies, normal lips, palate, and epiglottis [Saldino and Noonan, 1972; Spranger et al., 19741. SRPS 1 [Saldino-Noonan] and SRPS 111 VermaNaumoff)are thought to be allelic disorders representing variability in expression of the same mutation or different mutations at the same gene locus [Silence, 1980; Bernstein et al., 19851. They have many clinical and radiographic findings in common but can be differentiated by the configuration at the ends of long bones (pointed in type 1 and rounded with lateral spiculation in type 1111, short cranial base, and horizontal tridentshape acetabular margins (type 111) [ Yang et al., 1980, Bemstein et al., 1985;Silence et al., 19871.Beemer et al. [19831 described a new form of short-rib syndrome that shared most of the manifestation of SRPS 11but without polydactyly [Winter, 1988; Chen et al., 1989; van Maldergem et al., 19901. Yang et al. [19871 first suggested the term “Beemer short rib syndrome.” A case of the Beemer short rib syndrome with polydactyly was reported by Yang et al. [1991]. They recommended the eponym “Beemer-Langer” and used the abbreviation SR(P)S to indicate variable polydactyly. Though different subtypes of SRPSwas proposed to clarify this confusing syndrome [Spranger and Maroteaux, 19901, some authors have suggested that the SRPS are a single entity with varying expressivity [Bidot-Lopezet al., 1978; Silence, 1980; Walley et al., 1983; Bernstein et al., 19851. We report on a case that cannot be definitely categorized into the above mentioned forms, yet possesses some of the manifestations of al1 forms. These observations seem to support the contention of a single entity with varying expressivity.
CLINICAL REPORT A 36-year-oldwoman, gravida 3 para 2, a t 32 + weeks of gestation, was noted to carry a fetus with multiple abnormalities including macrocephaly, occipital bone defect, short limbs, and omphalocele by sonographic exReceived for publication July 15, 1991; revision received Janu- amination. The nonconsanguineous couple already had 2 healthy girls, and termination of the pregnancy was ary 22, 1992. requested. Cesarean section was performed due to macAddress reprint requests to Yung-Chieh Tsai, M.D., Department of Obstetrics and Gynecology, Chang Gung Memorial Hospi- roceph a1y. The male baby died immediately after birth. Gross tal, 123,TA Pei Rd., Niao Sung Kaohsiung, Taiwan, R.O.C.
O 1992 Wiley-Liss,
Inc.
32
Tsai et al.
Fig. 1. Postmorkm photograph of the fetus (see text for description).
Fig. 3. Postaxial polysyndactyly (left hand).
postmortem findings included (Figs. 1-4):generalized hydrops fetus with a 3,400gm body weight, 38 cm body length, head circumference 41 cm, chest circumference 39 cm, and an abdominal circumference 42 cm. He also had micromelic dwarfism with flattened face, prominent forehead, ocular hypertelorism, prominent epicanthal folds, small, flat, and apparently low-set hypoplastic ears. The hard palate was intact. There was a deep fissure in the midline of the upper and lower lips; the tongue was normal. The neck was relatively short. Marked edeme was noted over the scalp, face, and neck. The chest was symmetrical but rather small in size. The
Fig. 2. Deep fissure in the upper and lower lips of the fetus.
Fig. 4. Postaxial polysyndactyly of legs.
abdomen was distended and soft. An omphalocele measuring 8 x 6.5 cm with umbilical cord carrying 2 arteries and one vein was noted. The externa1 genitalia were normal. The anus was patent with meconium staining. "he back showed no deformity with the spine palpable in the midline. The limbs were short with post-axial polysyndactyly of al1 limbs (6 fingers on each of the 4 limbs). An encephalocele protruded from the occipital bone. In addition, there were situs inversus totalis with bilateral pulmonary hypoplasia and right renal hydronephrosis. "he other interna1 organs appeared grossly normal. Microscopically, the epiphyseal growth plates from
SRP Syndrome
tubular bone were attenuated with short proliferative cell columns and irregular chondro-osseoustransformation. No PAS-positive intracytoplasmic granules or inclusion bodies were observed. Radiographs of the skeleton (Figs. 5-8) indicated an occipital bone defect with flat basal angle and a rectilinear mandible with an obtuse mandibular angle, short ribs with widening of anterior ends. Small scapulae and short tubular bones with bowing of the radii, ulnae, and femora. Metaphyseal irregularity with spiking was noted in the fibula. Round dista1 ends of the femora and tibiae were noted. The number and configuration of vertebrae were normal, as was the pelvis. Polysyndactyly was present in al1 4 limbs. Chromosomes were apparently normal
(46XY). DISCUSSION The presence of short horizontal ribs, hypoplastic lung, polydactyly severe micromelia, and generalized systemic abnormalities placed this case into the category of SRPS. However, it becomes difficult when one tries to classify it into the specific types of SRPS. Table 1 illustrates the different types in comparison with our case. F’rom this table, it is obvious that SRPS 1and 111 can be ruled out because of the absence of typical metaphyseal irregularity. It is also unlikely that our case is a type 11 SRPS because the ovoid tibiae are absent. Beemer et al. [19831 have described a new form of SRPS that shared most of the manifestations of SRPS 11but without polydactyly. They are characterized clinically by median cleft lip with or without cleft palate, small chest with extremely short ribs, protuberant abdomen with omphalocele, and radiographically by bowing of the radius and ulnar, small ilia, and normal tibiae, which is longer than fibula. A case that mimicked Beemer short rib syndrome but with polydactyly was reported by Yang et al. [19911. They thus proposed that the Beemer short rib syndrome was actually a condition of short rib (polydactyly) syndrome. The abbreviation SR(P)S was used to indicate variable polydactyly and the eponym “Beemer-Langer” was recommended. Comparison of our case with some of Beemer-Langer type of SR(P)S [Beemer et al., 1983; Winter, 1988; van Maldergem et al., 1990; Lin et al., 1991; Yang et al., 19911 is tabulated in Table 11. Though our case has many common findings with the BeemerLanger type of SR(P)S,the characteristic cleft lip with or without cleft palate is absent. Besides, the histopathologic findings of attenuated epiphyseal proliferative zone with irregular chondro-osseous transformation in our case are also different from published cartilage histopathology of the Beemer-Langer type of SR(P)S [Beemer, 1987; Chen et al., 1989; Yang et al., 1987; Garcia et al., 1989; Lin et al., 1991; Yang et al., 19911. Spranger and Maroteaux [1990] proposed that there were at least 7 types of SRPS, which included type 1 (Saldino-Noonan),type 11(Verma-Naumoff),type 111(Le Marec), type IV (Yang),type V (Jeune),type VI (Majewski), type VI1 (Beemer). In their new classification, type 111 (Le Marec), IV (Yang), and V (Jeune) are new subtypes. Type 111 (LeMarec) of SRPS basically resembles
Fig. 5. Postmortem AP radiograph of the fetus.
Fig. 6. Occipital bone defect with flat basal angle.
33
34
Tsai et al.
Fig. 7. Bowing of the radii and ulnae.
Fig. 8. Lateral speculation of the fibula.
Saldino-Noonon and Verma-Naumoff types of SRPS, but the ribs are not as short as in SRP 1 and 111 and the femora are relatively well formed with round proximal ends. m e IV SRPS (Yang) is characterized by peculiar deformity of the ulna and less markedly of the radius, cleft lip/palate, and cytoplasmic inclusions in chondrocytes of the resting cartilage. Asphyxiating thoracic dysplasia, which has much longer ribs than other SRPS, is considered as type V (Jeune) in their report. The
different findings between their types 111,IV, and IV and our case are apparent, and obviously this case cannot be categorized into any of them. Kozlowski et al. [19771 reported on a case with many findings similar to SRPS type 11but without ovoid tibia and cleft lip/palate. It was later regarded as an atypical form of SRP 11by Cherstvoy et al. [19801. Our case had many similar abnormalities as his. Wider variations, such as bilateral lateral spur formation of the fibulae,
SRP Syndrome
35
TABLE 1. Distinctive Manifestations of Different m e s of SRPS and the Findings in This Case m e1 (Saldinop p e 11 Noonon) (Majewski)
Distinctive trait Externa1 appearance Polydactyly Syndact yly Flat face Flat occiput Cleft liplpalate Rudimentary epiglottis Hydrops Radiological abnormalities Metaphyseal dysplasia Pointed Round with lateral spiculation Ovoid tibia Pelvic abnormalities Vertebral abnormalities Short cranial base Triangular ossification defect (lat. aspect of acetabulum)
+ + + + -1-
+ +-
+ + +
+-
+
+/+
+ +
+
-
+
This case
+
+ -
' s p e 111 (VermaNaumoM
-
-
+
-
-
+ + + +
++/-
-
+
-
+-
encephalocele deep fissure
-1-
minimal -
-
+-
+
TABLE 11. Comparison of the SR(P)SBeemer-Langer Type with This case Beemer (1) (2) Macrocephaly Flat face Cleft liplpalate Ascites Omphalocele Short ribs Small scapulae Short tubular bone Metaphyseal irregularity Bowing of radiitulnae Bowing of femora Polydactyly Familv historv
+
+ +/+ + + + + ++
minimal -
consancr
+ + +/+ + + + ++
min im a1 -
Winter
Maldergem
Lin
Yang
+
+ + +/+ + + + + + minimal +-
+
+
+
+/+
+ + + + + min im a 1 + -
+
+
+ + + + +-
+ + + + + + +
+la +/+
-
-
-
-
+
This Case
+
+ deep fissure + + + +
-
+ +
min im a1 min im a1
+ -
"Grooved palate.
bowed radii and ulnae, omphalocele, encephalocele, and complete situs inversus, were also present. Whether our case should be considered as an atypical form of SRP 11 or another variation of Beemer-Langer type of SR(P)S remains to be determined. According to Bernstein's view, SRPS is a single syndrome with a wide spectrum of anatomical abnormalities. The skeletal manifestations are the most dramatic finding and the generalized systemic abnormalities of al1 organ systems seem to suggest a defect in regulation of cellular differentiation during early embryogenesis [Bernstein et al., 19851. The findings in our case consisting of parts of al1 known SRPS types further support this contention.
ACKNOWLEDGMENTS We gratefully acknowledge the assistance and the review of the manuscript by Dr. John M. Opitz, Department of Medical Genetics, Shodair Children's Hospital, Helena, MT. We also thank Miss Chyung-Mei Yeh for typing this manuscript.
REFERENCES Beemer FA (1987):Short rib syndrome classification. Am J Med Genet [Suppl] 3:209-210. Beemer FA, Langer LO Jr, Klep-de Pater JM, Hemmes AM, Bylsma JB, Pauli RM, Myers TL, Haws 111CC (1983): Anew short rib syndrome: Report of two cases. Am J Med Genet 14:115-123. Bernstein R, Isdaie J , Pinto M, Du Toit Zaaijman J, Jenkins T (1985): Short rib-polydactyly syndrome: a single or heterogenous entity? A re-evaluation prompted by four cases. J Med Genet 2246-53. Bidot-Lopez P, Ablow RC, Ogden JA, Mahoney MJ (1978): A Case of Short Rib Polydactyly. Pediatrics 61(3):427-432. Cherstvoy ED, Lurie IW, Shved iA,Lazjuk GI, Ostrowskaya TI, Usoev SS (1980): Diffculties in classification of the short rib-polydactyly syndrome. Eur J Pediatr 133(1):57-61. Chen K, Mckeever PA, Young ID (1989): Short rib syndrome without polydactyly. J Med Genet 26346-347. Cooper CP, Hall CM (1982): Lethal Short-Rib Polydactyly Syndrome of the Majewski Type: A Report of Three Case. Ped Radio1 144:513517. Garcia H, Drescher H, Kuchelmeister K, Lenz W, Roessner A (1988): Short rib-polydactyly syndromes. Klin Padiatr 200(2):140-144.
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Tsai et al.
Kozlowski K, Masel J, Morris L, Ryan J , Collins E, Van Vliet P, Woolnough H (1977):Neonatal Death Dwarfkm (Report of 17 cases). Aust Radiol 21:164-183. Lin AE, Doshi N, Flom L, Tenenholz B, Filkins KL (1991):BeemerLanger Syndrome With Manifestations of a n Orofaciodigital syn&me. Am J Med Genit 39(3):247-251. Majewski F, Pfeiffer RA, Lenz W, Muller R, Feil G, Seiler R (1971): Polysyndactyly, short limbs, and genital rnalformations-a new syndrome? Z Kinderheilkd 111(2):118-138. Motegi T, Kusunoki M, Nishi T,Hamada T, Sato N, Irnamura T,Mohri N (1979):Short Rib-Polydactyly Syndrome, Majewski Type, in Two Male siblings. Hum Genet 49:269-275. Naumoff P, Young LW, Mazer J , Amortequi AJ (1977):Short rib polydactyly Syndrome Type 3.Ped Radiol 122:443-447. Saldino RM, Noonan CD (1972):Severe thoracic dystrophy with striking micromelia, abnormal osseous development, including the spine, and multiple visceral anomalies. Arn J Roentgenol 114(3):257-263. Silence D, Kozlowski K, Bar-Ziv J, Fiihrurnann-Rieger A, Fuhrmann W, Pascu F (1987):Perinatally lethal short rib-polydactyly syndromes. 1.Variability in known syndromes. Pediatr Radiol 17:474480. Silence DO (1980):Invited editorial comment Non-Majewski short ribpolydactyly syndrome. Arn J Med Genet 7:223-229. Spranger J, Grirnm B, Weller M, WeiBenbacher G,Hemnann J, Gilbert E,Krepler R (1974):Short Rib-Polydactyly (SRP) syndrome, Types Majewski and Saldino-Noonan. Z Kinderheilk 116(2):73-94.
Spranger J, Maroteaux P (1990):The lethal osteochondrcdysplasias. Advances in Human Genetics 19:l-103. van Maldergern L, Gillerot Y, Salmin E, Verloes A, Koulischer L (1990): Lethal short-rib with median cleft and without polydactyly: a fourth case. Pediatr Radiol 20367-368. Verma IC, Bhargava S,Agarwal S (1975):An autosomal recessive form of lethal chondrodystrophy with severe thoracic narrowing, rhizoacromelic type of rnicrornelia, polydactyly and genital anomalies. Birth defects 11(6):167-174. Walley VM, Coates CF, Gilbert JJ, Valentine GH, Davies EM (1983): Brief Clinical Report: Short Rib-Polydactyly Syndrome, Majewski Type. Am J Med Genet 14:445-452. Winter RM (1988):A lethal short-rib without polydactyly. J Med Genet 25349-357. Yang SS, Langer LO, Cacciarelli A, Dahms BB, Unger ER, Roskarnp J, Dinno ND, Chen H (1987):Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib-polydactyly syndrorne spectrurn: A clinicopathologic study. Am J Med Genet [Suppl] 3:191-207. Yang SS, Lin CS, Al Saadi A, Nangia BS, Bemstein J (1980):Short ribpolydactyly syndrome, type 3 with chondrocyte inclusion: report of a case and review of the literature. Am J Med Genet 7(2):205-213. Yang SS, Roth JA, Langer LO Jr (1991):Short Rib Syndrorne Beemer Langer Type With Polydactyly: A Multiple Congenital Anomalies Syndrome. Arn J Med Genet 39(3): 243-246
