American Journal of Medical Genetics 40230-233 (1991)

Short Rib Syndrome-Beemer Type in Sibs Raoul C.M. Hennekam Clinical Genetics Center Utrecht, Utrecht, The Netherlands

The short rib (polydactyly) syndrome Beemer type is a rare lethal osteochondrodysplasia characterized clinically by short limbs, me- dian cleft upper lip and palate, narrow tho- rax, and protuberant abdomen, and radiolog- ically by short ribs, short and bowed long bones, and mild platyspondyly. Two affected female sibs are described, one having a preax- ial polydactyly of the feet. The differentiation with the short rib syndrome Majewski type relies mainly on the radiological appearance of the tibia. Molecular biology may eventually prove whether the 2 conditions are truly sepa- rate entities or not.

KEY WORDS: osteochondrodysplasia, short rib syndromes, Beemer type, Majewski type, polydactyly

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INTRODUCTION The classification and nomenclature of the short rib

(polydactyly) syndromes (SRS) are confusing at best [Yang et al., 19873, and may be considered a garden of Eden for splitters and lumpers. For instance the patients described by Verma et al. [19751 and Naumoff et al. [19771 were first thought to be separate entities, then considered to be examples of the Saldino-Noonan type of SRS [Sillence, 19801, but later again split off as prob- ably separate conditions [Spranger, 19891. It was first named SRS type I11 [Naumoff et al., 19771, but the condi- tion labeled SRS type I11 in the 1983 International No- menclature of Constitutional Diseases of Bone is SRS Beemer type [Yang et al., 19871. Still, even recently SRS Verma-Naumoff type was called SRS type I11 again [Garcia et al., 19881.

Spranger [19891 divided the lethal short rib syn- dromes in 7 subtypes: asphyxiating thoracic dysplasia, Saldino-Noonan type, Verma-Naumoff type, Yang type, Le Marec type, Majewski type, and Beemer type. The SRS Beemer type was delineated by Beemer et al.

Received for publication May 24,1990; revision received Septem- ber 3, 1990.

Address reprint requests to Raoul C.M. Hennekam, M.D., Ph.D. Clinical Genetics Center Utrecht, P.O. Box 18009, 3501 CA Utrecht. The Netherlands.

0 1991 Wiley-Liss, Inc.

[19831. Probably the patients described by Black et al. [1982] represent the same condition. To date 11 patients have been described [Black et al., 1982; Beemer et al., 1983; Passarge, 1983; Beemer, 1987; Winter, 1988; Gar- cia et al., 1988; Chen et al., 1989; Dominick, 19901. Here we present 2 sibs with SRS Beemer type, one with and one without polydactyly.

CLINICAL REPORTS Case 1

Case 1 was the second-born child of healthy, noncon- sanguineous parents (father 29 and mother 27 years old, respectively). Their first child, a girl, was normal. At 29 weeks of gestation hydramnios was detected clinically. Ultrasound examination showed a growth-retarded fetus with hydrops and ascites, eventually leading to induction of delivery at 30 weeks of gestation. The child was stillborn.

Postmortem examination showed a grossly abnormal female child (Fig. 11, weighing 1375 g (50th centile), and with a length of 33 cm (<3rd centile). She was hydropic, and had a bulging forehead, broad nasal bridge, and median cleft upper lip and palate. The thorax was short and narrow, the abdomen distended, and the external genitalia normal. The limbs were short and broad. There was no polydactyly. Internal anomalies included hydrocephalus internus, cardiovascular anomalies (atresia of the ascending aorta, ventricular septa1 de- fect, patent foramen ovale), and intestinal malrotation with very short ileum and jejunum. Chromosomes were normal female, 46,XX.

Radiographs (Fig. 2) showed very short ribs, mild platyspondyly, small iliac bones, and short and some- what bowed long bones. The tibiae were not ovoid- shaped, and metaphyses were normally formed.

Case 2 The third child was born at a gestational age of 30

weeks. Delivery was induced because of severe growth retardation and hydrops on ultrasound examination. The child was stillborn.

Postmortem examination showed essentially the same anomalies as in the older sister (Fig. 3). In addi- tion, she had a preaxial polydactyly of both feet. Internal anomalies consisted of hydrocephalus internus, patent foramen ovale, and intestinal malrotation with a short ileum and jejunum. The postmortem radiographs (Fig. 4) showed virtually the same anomalies as in case 1, and

Short Rib Syndrome 231

Fig. 1. Case 1 (postmortem photo). Note large head, frontal bossing, cleft lip, narrow thorax, protuberant abdomen, and hydrops.

in addition the polydactyly of the feet. Chromosomes were normal female, 46,XX.

DISCUSSION The clinical and radiological findings in the 11 pa-

tients from the literature are compared to those of the present sibs in Table I. The major clinical characteristics are short limbs, median cleft upper lip and palate, nar- row thorax, protuberant abdomen, ascites, and hydrops. Cardiac and intestinal anomalies may be present. The main radiologic features are very short ribs, short and often bowed long bones, and mild platyspondyly. The tibia is not very short and there is no metaphyseal irregularity. The occurrence of the disorder in both sexes with equal severity, the consanguinity in 2 instances [Black et al., 1982; Beemer et al., 19831, and the lack of symptoms in the parents all point to an autosomal reces- sive pattern of inheritance.

The discrimination between SRS Beemer type and SRS Majewski type is difficult, if not impossible, on clinical grounds only. Polydactyly has been the most

important differentiating characteristic, but the pres- ence of polydactyly in one of the presently reported sibs, and in another patient studied by Spranger [Beemer, 19871, makes this a less reliable sign. Although a rudi- mentary epiglottis and kidney abnormalities are not often reported in SRS Beemer type, they may be present [Black et al., 1982; Beemer et al., 1983; Passarge, 19831. All other internal anomalies may be found in both disor- ders, but in differing frequencies. The differences in radiologic studies are the lack of platyspondyly, and above all the presence of the very short ovoid tibiae in SRS Majewski type. To the best of our knowledge no familial cases have been described in which one case had such shaped tibiae, and the other did not. Until this has been reported, it seems prudent to separate the 2 condi- tions [Yang et al., 19871. Eventually molecular biology may prove whether the differences between SRS Beemer type and SRS Majewski type are caused by genetic het- erogeneity or by variability of expression.

ACKNOWLEDGMENTS I am indebted to Drs. F.A. Beemer (Utrecht, The

Netherlands) and H. Chr. Dominick (Ludwigshafen, BRD) for further information on their patients.

REFERENCES Beemer FA (1987): Editorial comment: Short-rib syndrome classifica-

tion. Am J Med Genet Suppl 3:209-210. Beemer FA, Langer LO, Klep-De Pater JM, Hemmes AM, Bijlsma 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.

Black IL, Fitzsimmons J , Fitzsimmons E, Thomas AJ (1982): Parental consanguinity and the Majewski syndrome. J Med Genet 19:141- 157.

Chen K, McKeever PA, Young ID (1989): Short rib syndrome without polydactyly. J Med Genet 26:346-349.

Dominick HChr (1990): Personal communication. Garcia H, Drescher H, Kuchelmeister K, Lenz W, Roessner A (1988):

Short rib-polydactyly syndromes. Klin Padiatr 200:140-144. Naumoff P, Young LW, Marer J , Amortegui AJ (1977): SHort-rib-

polydactyly syndrome type 111. Radiology 122:443-447. Passarge E (1983): Letter to the editor: Familial occurrence of a short

rib syndrome with hydrops fetalis but without polydactyly. Am J Med Genet 14:403-405.

Sillence DO (1980): Invited editorial comment: Non-Majewski short rib-polydactyly syndrome. Am J Med Genet 7:223-229.

Spranger J (1989): Radiologic nosology of bone dysplasias. Am J Med Genet 34:96-104.

Verma IC, Bhargavas, Agarwal S (1975): An autosomal massive form of lethal chondrodystrophy with severe thoracic narrowing, rhizoacromelic type of micromelia, polydactyly and genital anoma- lies. Birth Defects OAS XI (b):167-174.

Winter RM (1988): A lethal short rib syndrome without polydactyly. J Med Genet 25349-350.

Yang SS, Langer LO, Cacciarelli A, Dahms BB, Unger ER, Roskamp J , Dinno ND, Chen H (1987): Three conditions in neonatal asphyxiat- ing thoracic dysplasia (Jeune) and short rib-polydactyly syndrome spectrum: A clinicopathologic study. Am J Med Genet Suppl3:191- 207.

232 Hennekam

Fig. 2. Radiographs of case 1. Note very short ribs, small iliac bones, platyspondyly, and short and bowed long bones.

Fig. 3. Case 2 (postmortem photo). Note resemblance with case 1 and preaxial polydactyly of the feet. Fig. 4. Radiographs of case 2. Note resemblance with case 1.

Short Rib Syndrome 233

TABLE I. Comparison of the Findings of the Present Cases With SRS Beemer Type Compared to Those From the Literature*

2 M <3

3 F

5 6 7 8 M M M F 10 50 <3

+ + + + + + + + +

9 M 15

10 F

<3

13 Total F 8F/5M 25

+ 11/12 + 10111 + loll0 + 10111

2/10

+ 11/13 + 13/13

5/13

+ 10/12 + 8/12

5/11 + 8/11

+ 5/11

- 2/12 3/10 + 13/13

+ 1/13

+ 13/13 + 11/12

+ 6/12 + 7/12 + 13/13 + 9/12

-

-

-

-

1 F

<3

4

F 25

11 F

<3

12 F

<3 Sex Birth length

(centile) Macrocephaly Frontal bossing Flat nasal bridge Median cleft upper

lip and palate Rudimentary

epiglottis Hy drops Narrow thorax Cardiovascular

anomalies Distended abdomen Ascites Omphalocele Intestinal

malrotation Gastrointestinal

anomalies Kidney anomalies Genital anomalies Short limbs Preaxial

polydactyly Short ribs Highly placed

clavicles Platyspondyly Small iliac bones Short long bones Bowed long bones

+ + + +

+ + + +

+ + + +

+ + + +

+ + + -

+ + + +

+ + + + 4-

+ + + + +

+ + + + + -

+ + +

+ + -

+ + +

+ + +

+ + + -

+ + + -

+ + + +

+ + + +

+ + + -

+ - + 4-

+ + +

- + - +

+ + + + - - - -

+ + + + + + + + + +

+ + +

+ + + + + + + + + + + +

+ + + +

+ + + +

+ + + -

- + + + + + + + + - +

- -

+ + * M, male; F, female; + , present; - , absent; centiles at birth length according to gestational age. References: 1, Black et al. [19821; 2-4, Beemer et al. [1983]; 5-6, Passarge [1983]; 7, Beemer [19871; 8, Winter [19881; 9, Garcia et al. [1988l; 10, Chen et al. [19891; 11, Dominick [19901; 12-13, present cases. Two cases [Beemer et al., 1983; Beemer, 19871 are not tabulated because of lack of sufficient data.