Humangenetik 28, 353--356 (1975) © by Springer-Verlag 1975
The Tetraphocomelia -- Cleft Palate Syndrome* D e s c r i p t i o n o f a N e w Case F. R . Grosse, C. P a n d e l , a n d H. R . W i e d e m a n n University of Kiel, Medical School, Department of Pediatrics Received April 10, 1975
Summary. A new case of Tetraphocomelia--eleft palate syndrome is described. The similiarity between this patient and the cases classified as Pseudothalidomide or as Robert syndrome makes a distinction between these 2 syndromes doubtful. Zusamrnen/assung. Ein Fall von Tetraphokomelie und Oberkieferspalte wird beschrieben. Die )[hnlichkeit dieses :Patienten mit l~SAlen, die als Pseudothalidomid- oder Robert-Syndrom eingeordnet werden, 15A3t die Frage aufkommen, ob eine Unterscheidung dieser beiden Syndrome sinnvoll ist. Introduction P h o c o m e l i a is p a r t o f a m a l f o r m a t i o n s p e c t r u m in 4 a p p a r e n t l y well d e f i n e d s y n d r o m e s : as t e t r a p h o c o m e l i a in t h e P~oberts a n d P s e u d o t h a l i d o n l i d e s y n d r o m e a n d u s u a l l y as P h o c o m e l i a o f a n u p p e r e x t r e m i t y in t h e H o l t - O r a m a n d t h e Radius-Platelet Hypoplasia syndrome. We are describing here a malformed infant with the main manifestations of t e t r a p h o c o m e l i a a n d cleft p a l a t e , f i t t i n g b o t h t h e P s e u d o t h a l i d o m i d e s y n d r o m e (PTS) a n d t h e R o b e r t s s y n d r o m e (RS). W e t h e r e f o r e b r i n g u p t h e q u e s t i o n w h e t h e r a d i f f e r e n t i a t i o n b e t w e e n t h e s e 2 s y n d r o m e s is justified.
Case Report The father and the mother of our patient C. K. were 31 and 24 years old, respectively, when the child was born. Both parents were healthy and there was no hint for consanguinity. An older and a younger sib of C. K. were normal and the same was said about other near relatives. C. K. was born spontaneously 11 days post expected date on 3-19-70. Pregnancy was complicated by an albuminuria in the second and third months, for which the pregnant was treated with an unknown medication. APGAI~ was 8. Birth weight, length and head circumference were 1910 g, 40 cm, and 32 cm respectively. She was seen by us immediately after delivery and at the age of 4 ~ years for surgical procedures, and these are the combined findings of the 2 admissions. 0nly one umbilical artery; microeephaly (head circumference at the second admission 46 cm), prominent metopic suture; fine silvery-blond hair; absent ear lobes; capillary heman* The application of the term phoeomelia for the malformation of the here described ease is certainly not exact in the strict sense of the word. But we feel justified to do so because of the general use of the term in the literature, because of MeKusick's suggestion to call the Pseudothalidomide or SC-syndrome the SC-Phocomelia-syndrome (Birth defects Original Article Series, Part III, Vol. 5, p. 89) and because of the definition of phoeomelia as total or partial absence of any proximal region of the limbs by Feire-Maia (ibid. p. 8/9).
354
F. I~. Grosse et al. Fig. l a and b. Patient at the age of 4 ~ years. For description see text
Fig. 2. Full body X-ray at the age of 2 days Fig. 3. X-ray of the pelvis. Age 41/2 years gioma of glabella and lids; prominent nasal septum, hypoplastic alae nasi; hypotelorism; bilateral convergent strabism; bilateral epieanthic folds; midline cleft of the hard and soft palate; development of a round, firm displacable mass in front of the larynx after the fourth month of life. Short forearms; radii not palpable; limitation of extension in the elbow-joints; markedly radiMly deviated hands with shortened abducted thumbs and hypoplastic indices; short clinodactylous fifths fingers; partial cutaneous syndactyly between fingers 3 and 4 and 4 and 5; extremely short legs apparently without knee-joints, the left leg being externally rotated; pes adductas bilaterally, more on the right than the left (Fig. 1 a and b). X-ray examinations (skeletal survey) confirmed our clinical findings and revealed in addition: plump claviculae, ratber high and short body of the vertebrae; high and narrow pelvis with horizontal pubic bones and rudimentary ischiae bones; complete absence of the
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radii; plump proximal portion of the ulnae; on the right y-shaped fusion of the first and second and of the fourths and fifths metacarpal bones; on the left complete fusion of the first 2 metacarpals, the thumb articulating with the radio-distal area of the "first" metacarpal and the index in the usual manner with the distal aspect; again y-shaped fusion of the metacarpals 4 and 5; only one long bone of the legs present, presumably the tibia; bilaterally proximal fusion of the fourth and fifths metatarsal bone; somewhat hypoplastie middle and distal phalanges of the toes (Figs. 2 and 3). IVP and gastro-intestinM X-ray were normal. Routine laboratory tests brought normal results as well as a chromosome analysis. Dermatoglyphics markedly hypoplastie, the skin on the volar aspects being orange peel like. On the right from thumb to little finger one ulnar loop and four whorls, on the left five whorls. Completely irregular and hypoplastic flexion creases on the palms, increased white lines. Because of swallowing difficulties the child was fed via a naso-gastric tube during infancy. In the first few days she developed a light respiratory distress syndrome. Her psychomotor development turned out to be very slow; at age of 41/2years she did not speak, but was happy, active, and alert, and easy to get in contact with. She could sit and crawl on her extremities. Her weight was commensurate with her height of 64 cm and her head circumference was 46 em. At this age also her cleft palate was repaired and the prelaryngeal mass excised which proved to be an epidermoid cyst.
Discussion The m a n i f e s t a t i o n s this child p r e s e n t e d w i t h are in s u m m a r y : 1. complete cleft of t h e p a l a t e , 2. n e a r l y s y m m e t r i c r e d u c t i v e m a l f o r m a t i o n s of t h e limbs, 3. p r i m a r y shortness of s t a t u r e , 4. m u l t i p l e m i n o r anomalies of t h e face a n d skull e.g. microg n a t h i a , h y p o p l a s t i c cartilages of t h e nose, c a p i l l a r y h e m a n g i o m a , s i l v e r y - b l o n d hair, 5. m e n t a l r e t a r d a t i o n . The s p e c t r u m of these m a l f o r m a t i o n s fits r a t h e r e x a c t l y t h e P T S as described b y H e r r m a n n et al. (1969) a n d Lenz (personal c o m m u n i c a tion), b u t t h e r e is considerable o v e r l a p on t h e R S : cleft p a l a t e has been described o n l y in case 4 of t h e P T S ( H e r r m a n n et al., 1969) in c o m b i n a t i o n w i t h cleft lip, b u t in cases 1 a n d 2 t h e p a l a t e was felt to be h i g h l y arched. I n t h e RS, however, cleft lip-palate, u s u a l l y bilateral, is a f a i r l y c o n s t a n t feature. Absence of t h e f e m u r - - a s in our e a s e - - i s n o t k n o w n to be p a r t of t h e P T S , b u t case 2 h a d s h o r t femurs. I n t h e R S on t h e o t h e r h a n d no f e m u r was p r e s e n t b i l a t e r a l l y in 6 a n d u n i l a t e r a l l y in 1 of 22 eases collected b y F r e e m a n et al. (1974). H y p e r t e l o r i s m is a l m o s t always m e n t i o n e d in t h e I~S b u t in o n l y one of t h e 4 cases of PTS, our case showed hypotelorism. The difficulties to d i s c r i m i n a t e e x a c t l y b e t w e e n these 2 s y n d r o m e s becomes s t r i k i n g l y a p p a r e n t b y looking a t t h e classification of some cases b y H e r r m a n n et al. ( 1 9 6 9 ) - - t h e first describers of t h e P T S - - a n d b y F r e e m a n et al. who p e r f o r m e d t h e m o s t r e c e n t review on t h e R S : The 2 cases of O ' B r i a n a n d M u s t a r d (1929) - - 2 sibs whose p a r e n t s were double first c o u s i n s - - i m p r e s s e d H e r r m a n n et al. as p r o b a b l e e x a m p l e s of t h e PTS, while F r e e m a n et al. classified t h e i n d e x case as R S a n d t h e sib as questionable RS. The case of A p p e l t et al. (1966) is n o t definitely e x c l u d e d from t h e P T S b y H e r r m a n n et al., b u t listed as e x a m p l e of t h e R S b y F r e e m a n et al. Because of these difficulties t h e p r e s e n t a u t h o r s are inclined n o t to differentiate between these two s y n d r o m e s until t h r t h e r criteria for differential diagnosis arise. W e do n o t w a n t to s a y t h a t 2 such s y n d r o m e s a c t u a l l y do n o t exist, b u t we w a n t to s t a t e t h a t a t t h e p r e s e n t t i m e t h e y c a n n o t be d e m a r c a t e d w i t h c e r t a i n t y from each other.
356
F. 1~. Grosse et al.
The inheritance of this (these) syndrome(s) is autosomal recessive a n d therefore from the s t a n d p o i n t of genetic counselling it is certainly no m i s t a k e to lump. The degree of the malformations respectively their presence can be explained b y different expressivity of the m u t a n t genes. B u t we w a n t to repeat our above statem e n t in different words: heterogeneity c a n n o t be excluded. After a review of the literature (Doerffer, 1928; E n g e l h a r t a n d Pischinger, 1939; Falk, 1908 ; Grille, 1963 ; Gruber, 1937 ; Krueger, 1906 ; Mayer, 1829 ; O ' B r i a n a n d Mustard, 1921; Slingenberg, 1908; Stroer, 1939; Virchow, 1898; Weppler, 1937; W e r t h e m a n n , 1952) Appelt et al. a p p a r e n t l y were the first to recognize the comb i n a t i o n of tetraphocomelia a n d clefts of the maxilla as a syndrome. T h e y unf o r t u n a t e l y missed the short c o m m u n i c a t i o n of R o b e r t s (1919) whose n a m e now is a t t a c h e d to this syndrome, at least in the English literature.
References Appelt, H., Gerken, H., Lenz, W. : Tetraphokomelie mit Lippen-Kiefer-Gaumenspalte und Clitorishypertrophie - - Ein Syndrom. Paediat. Paedol. 2, 119--124 (1966) Doerffer, C. : Ein Fall yon Phokomelie. Mschr. Geburtsh. Gyngk. 72, 195--198 (1926) Engelhart, E., Pisehinger, A. : Uber eine durch RSntgenstrahlen verursachte menschliche MiBbildung. Mfinch. med. Wschr. 86, 1315--1316 (1939) Falk, E.: Eine seltene menschliche Mililbildung und ihre Bedeutung ffir die Entwicklungsgeschichte. Virchows Arch. path. Anat. 192, 544--564 (1908) Freeman, M. V. R., Williams, O. W., Schimke, R. ~q., Temtamy, S. A., Vachier, E., German, J.: The Roberts syndrome. Clin. Genet. 5, 1--16 (1974) Grille, 1%. A. : ~ber einen Fall yon Phokomelie. Dtsch. med. Wschr. 33, 1332--1333 (1963) Gruber, G. B. : Die Morphologie der Miflbildungendes Menschen und der Tiere (eds. E. Schwalbe, G. B. Gruber), Vol. 3, p. 310. Jena: Gustav Fischer 1937 Herrmann, J., Feingold, M., Tuffli, G. A., Opitz, J. M. : A familial dysmorphogenetic syndrome of limb deformities, characteristic facial appearance and associated anomalies: The "pseudothalidomide" or "SC-syndrome'. Birth Defects: Original Article Series, the first conference on the clinical delineation of birth defects, Part III. Limb malformations. New York, March, The National Foundation-March of Dimes, Vol. 5, pp. 81--89 (1969) Krueger, R. : Die Phocomelie und ihre ~berggnge, p. 92. Berlin: Verlag August Hirschwald 1906 Lenz, W. : Personal communication (1975) Mayer: Uber Verdoppelungen des Uterus und ihre Arten, nebst Bemerkungen fiber Hasenscharte und Wolfsrachen. J. Chir. Augenh. lg, 525 (1829); as quoted in Krueger (1906) O'Brian, H. R., Mustard, H. S. : An adult living case of total phocomelia. J. Amer. med. Ass. 77, 1964--1967 (1921) Roberts, J. B. : A child with double cleft lip and palate, protrusion of the intermaxillary portion of the upper jaw and imperfect development of the bones of the four extremities. Ann. Surg. g0, 252--253 (1919) Slingenberg, B. : MiBbildungen yon Extremitgten. Virchows Arch. path. Anat. 193, 1--92 (1908) Stroer, W. F. It. : ~ber das Zusammentreffen yon I-Iasenscharte mit ernsten Extremit~tenmiBbildung. Erbarzt 7, 101--107 (1939) Virchow, R. : Zeitschrift f. Ethnologic, 30. Jahrg., 1898, as cited by Krueger (1906), as case 65 Wepler, P. : Die sogenannte Fhokomelie. Dtsch. reed. Wschr. 63, 1302--1305 (1937) Werthemann, A. : Die EntwicklungsstSrungender Extremit~ten. In: Handbuch der speziellen pathologischen Anatomie und I-Iistologie, IX/6, p. 113. Berlin-GSttingen-Heidelberg: Springer 1952 Prof. Dr. H. R. Wiedemann Universit~ts-Kinderklinik D-2300 Kiel 1, FrSbelstraBe 15/17 Federal Republic of Germany
The Tetraphocomelia -- Cleft Palate Syndrome* D e s c r i p t i o n o f a N e w Case F. R . Grosse, C. P a n d e l , a n d H. R . W i e d e m a n n University of Kiel, Medical School, Department of Pediatrics Received April 10, 1975
Summary. A new case of Tetraphocomelia--eleft palate syndrome is described. The similiarity between this patient and the cases classified as Pseudothalidomide or as Robert syndrome makes a distinction between these 2 syndromes doubtful. Zusamrnen/assung. Ein Fall von Tetraphokomelie und Oberkieferspalte wird beschrieben. Die )[hnlichkeit dieses :Patienten mit l~SAlen, die als Pseudothalidomid- oder Robert-Syndrom eingeordnet werden, 15A3t die Frage aufkommen, ob eine Unterscheidung dieser beiden Syndrome sinnvoll ist. Introduction P h o c o m e l i a is p a r t o f a m a l f o r m a t i o n s p e c t r u m in 4 a p p a r e n t l y well d e f i n e d s y n d r o m e s : as t e t r a p h o c o m e l i a in t h e P~oberts a n d P s e u d o t h a l i d o n l i d e s y n d r o m e a n d u s u a l l y as P h o c o m e l i a o f a n u p p e r e x t r e m i t y in t h e H o l t - O r a m a n d t h e Radius-Platelet Hypoplasia syndrome. We are describing here a malformed infant with the main manifestations of t e t r a p h o c o m e l i a a n d cleft p a l a t e , f i t t i n g b o t h t h e P s e u d o t h a l i d o m i d e s y n d r o m e (PTS) a n d t h e R o b e r t s s y n d r o m e (RS). W e t h e r e f o r e b r i n g u p t h e q u e s t i o n w h e t h e r a d i f f e r e n t i a t i o n b e t w e e n t h e s e 2 s y n d r o m e s is justified.
Case Report The father and the mother of our patient C. K. were 31 and 24 years old, respectively, when the child was born. Both parents were healthy and there was no hint for consanguinity. An older and a younger sib of C. K. were normal and the same was said about other near relatives. C. K. was born spontaneously 11 days post expected date on 3-19-70. Pregnancy was complicated by an albuminuria in the second and third months, for which the pregnant was treated with an unknown medication. APGAI~ was 8. Birth weight, length and head circumference were 1910 g, 40 cm, and 32 cm respectively. She was seen by us immediately after delivery and at the age of 4 ~ years for surgical procedures, and these are the combined findings of the 2 admissions. 0nly one umbilical artery; microeephaly (head circumference at the second admission 46 cm), prominent metopic suture; fine silvery-blond hair; absent ear lobes; capillary heman* The application of the term phoeomelia for the malformation of the here described ease is certainly not exact in the strict sense of the word. But we feel justified to do so because of the general use of the term in the literature, because of MeKusick's suggestion to call the Pseudothalidomide or SC-syndrome the SC-Phocomelia-syndrome (Birth defects Original Article Series, Part III, Vol. 5, p. 89) and because of the definition of phoeomelia as total or partial absence of any proximal region of the limbs by Feire-Maia (ibid. p. 8/9).
354
F. I~. Grosse et al. Fig. l a and b. Patient at the age of 4 ~ years. For description see text
Fig. 2. Full body X-ray at the age of 2 days Fig. 3. X-ray of the pelvis. Age 41/2 years gioma of glabella and lids; prominent nasal septum, hypoplastic alae nasi; hypotelorism; bilateral convergent strabism; bilateral epieanthic folds; midline cleft of the hard and soft palate; development of a round, firm displacable mass in front of the larynx after the fourth month of life. Short forearms; radii not palpable; limitation of extension in the elbow-joints; markedly radiMly deviated hands with shortened abducted thumbs and hypoplastic indices; short clinodactylous fifths fingers; partial cutaneous syndactyly between fingers 3 and 4 and 4 and 5; extremely short legs apparently without knee-joints, the left leg being externally rotated; pes adductas bilaterally, more on the right than the left (Fig. 1 a and b). X-ray examinations (skeletal survey) confirmed our clinical findings and revealed in addition: plump claviculae, ratber high and short body of the vertebrae; high and narrow pelvis with horizontal pubic bones and rudimentary ischiae bones; complete absence of the
The Tetraphocomelia - - Cleft Palate Syndrome
355
radii; plump proximal portion of the ulnae; on the right y-shaped fusion of the first and second and of the fourths and fifths metacarpal bones; on the left complete fusion of the first 2 metacarpals, the thumb articulating with the radio-distal area of the "first" metacarpal and the index in the usual manner with the distal aspect; again y-shaped fusion of the metacarpals 4 and 5; only one long bone of the legs present, presumably the tibia; bilaterally proximal fusion of the fourth and fifths metatarsal bone; somewhat hypoplastie middle and distal phalanges of the toes (Figs. 2 and 3). IVP and gastro-intestinM X-ray were normal. Routine laboratory tests brought normal results as well as a chromosome analysis. Dermatoglyphics markedly hypoplastie, the skin on the volar aspects being orange peel like. On the right from thumb to little finger one ulnar loop and four whorls, on the left five whorls. Completely irregular and hypoplastic flexion creases on the palms, increased white lines. Because of swallowing difficulties the child was fed via a naso-gastric tube during infancy. In the first few days she developed a light respiratory distress syndrome. Her psychomotor development turned out to be very slow; at age of 41/2years she did not speak, but was happy, active, and alert, and easy to get in contact with. She could sit and crawl on her extremities. Her weight was commensurate with her height of 64 cm and her head circumference was 46 em. At this age also her cleft palate was repaired and the prelaryngeal mass excised which proved to be an epidermoid cyst.
Discussion The m a n i f e s t a t i o n s this child p r e s e n t e d w i t h are in s u m m a r y : 1. complete cleft of t h e p a l a t e , 2. n e a r l y s y m m e t r i c r e d u c t i v e m a l f o r m a t i o n s of t h e limbs, 3. p r i m a r y shortness of s t a t u r e , 4. m u l t i p l e m i n o r anomalies of t h e face a n d skull e.g. microg n a t h i a , h y p o p l a s t i c cartilages of t h e nose, c a p i l l a r y h e m a n g i o m a , s i l v e r y - b l o n d hair, 5. m e n t a l r e t a r d a t i o n . The s p e c t r u m of these m a l f o r m a t i o n s fits r a t h e r e x a c t l y t h e P T S as described b y H e r r m a n n et al. (1969) a n d Lenz (personal c o m m u n i c a tion), b u t t h e r e is considerable o v e r l a p on t h e R S : cleft p a l a t e has been described o n l y in case 4 of t h e P T S ( H e r r m a n n et al., 1969) in c o m b i n a t i o n w i t h cleft lip, b u t in cases 1 a n d 2 t h e p a l a t e was felt to be h i g h l y arched. I n t h e RS, however, cleft lip-palate, u s u a l l y bilateral, is a f a i r l y c o n s t a n t feature. Absence of t h e f e m u r - - a s in our e a s e - - i s n o t k n o w n to be p a r t of t h e P T S , b u t case 2 h a d s h o r t femurs. I n t h e R S on t h e o t h e r h a n d no f e m u r was p r e s e n t b i l a t e r a l l y in 6 a n d u n i l a t e r a l l y in 1 of 22 eases collected b y F r e e m a n et al. (1974). H y p e r t e l o r i s m is a l m o s t always m e n t i o n e d in t h e I~S b u t in o n l y one of t h e 4 cases of PTS, our case showed hypotelorism. The difficulties to d i s c r i m i n a t e e x a c t l y b e t w e e n these 2 s y n d r o m e s becomes s t r i k i n g l y a p p a r e n t b y looking a t t h e classification of some cases b y H e r r m a n n et al. ( 1 9 6 9 ) - - t h e first describers of t h e P T S - - a n d b y F r e e m a n et al. who p e r f o r m e d t h e m o s t r e c e n t review on t h e R S : The 2 cases of O ' B r i a n a n d M u s t a r d (1929) - - 2 sibs whose p a r e n t s were double first c o u s i n s - - i m p r e s s e d H e r r m a n n et al. as p r o b a b l e e x a m p l e s of t h e PTS, while F r e e m a n et al. classified t h e i n d e x case as R S a n d t h e sib as questionable RS. The case of A p p e l t et al. (1966) is n o t definitely e x c l u d e d from t h e P T S b y H e r r m a n n et al., b u t listed as e x a m p l e of t h e R S b y F r e e m a n et al. Because of these difficulties t h e p r e s e n t a u t h o r s are inclined n o t to differentiate between these two s y n d r o m e s until t h r t h e r criteria for differential diagnosis arise. W e do n o t w a n t to s a y t h a t 2 such s y n d r o m e s a c t u a l l y do n o t exist, b u t we w a n t to s t a t e t h a t a t t h e p r e s e n t t i m e t h e y c a n n o t be d e m a r c a t e d w i t h c e r t a i n t y from each other.
356
F. 1~. Grosse et al.
The inheritance of this (these) syndrome(s) is autosomal recessive a n d therefore from the s t a n d p o i n t of genetic counselling it is certainly no m i s t a k e to lump. The degree of the malformations respectively their presence can be explained b y different expressivity of the m u t a n t genes. B u t we w a n t to repeat our above statem e n t in different words: heterogeneity c a n n o t be excluded. After a review of the literature (Doerffer, 1928; E n g e l h a r t a n d Pischinger, 1939; Falk, 1908 ; Grille, 1963 ; Gruber, 1937 ; Krueger, 1906 ; Mayer, 1829 ; O ' B r i a n a n d Mustard, 1921; Slingenberg, 1908; Stroer, 1939; Virchow, 1898; Weppler, 1937; W e r t h e m a n n , 1952) Appelt et al. a p p a r e n t l y were the first to recognize the comb i n a t i o n of tetraphocomelia a n d clefts of the maxilla as a syndrome. T h e y unf o r t u n a t e l y missed the short c o m m u n i c a t i o n of R o b e r t s (1919) whose n a m e now is a t t a c h e d to this syndrome, at least in the English literature.
References Appelt, H., Gerken, H., Lenz, W. : Tetraphokomelie mit Lippen-Kiefer-Gaumenspalte und Clitorishypertrophie - - Ein Syndrom. Paediat. Paedol. 2, 119--124 (1966) Doerffer, C. : Ein Fall yon Phokomelie. Mschr. Geburtsh. Gyngk. 72, 195--198 (1926) Engelhart, E., Pisehinger, A. : Uber eine durch RSntgenstrahlen verursachte menschliche MiBbildung. Mfinch. med. Wschr. 86, 1315--1316 (1939) Falk, E.: Eine seltene menschliche Mililbildung und ihre Bedeutung ffir die Entwicklungsgeschichte. Virchows Arch. path. Anat. 192, 544--564 (1908) Freeman, M. V. R., Williams, O. W., Schimke, R. ~q., Temtamy, S. A., Vachier, E., German, J.: The Roberts syndrome. Clin. Genet. 5, 1--16 (1974) Grille, 1%. A. : ~ber einen Fall yon Phokomelie. Dtsch. med. Wschr. 33, 1332--1333 (1963) Gruber, G. B. : Die Morphologie der Miflbildungendes Menschen und der Tiere (eds. E. Schwalbe, G. B. Gruber), Vol. 3, p. 310. Jena: Gustav Fischer 1937 Herrmann, J., Feingold, M., Tuffli, G. A., Opitz, J. M. : A familial dysmorphogenetic syndrome of limb deformities, characteristic facial appearance and associated anomalies: The "pseudothalidomide" or "SC-syndrome'. Birth Defects: Original Article Series, the first conference on the clinical delineation of birth defects, Part III. Limb malformations. New York, March, The National Foundation-March of Dimes, Vol. 5, pp. 81--89 (1969) Krueger, R. : Die Phocomelie und ihre ~berggnge, p. 92. Berlin: Verlag August Hirschwald 1906 Lenz, W. : Personal communication (1975) Mayer: Uber Verdoppelungen des Uterus und ihre Arten, nebst Bemerkungen fiber Hasenscharte und Wolfsrachen. J. Chir. Augenh. lg, 525 (1829); as quoted in Krueger (1906) O'Brian, H. R., Mustard, H. S. : An adult living case of total phocomelia. J. Amer. med. Ass. 77, 1964--1967 (1921) Roberts, J. B. : A child with double cleft lip and palate, protrusion of the intermaxillary portion of the upper jaw and imperfect development of the bones of the four extremities. Ann. Surg. g0, 252--253 (1919) Slingenberg, B. : MiBbildungen yon Extremitgten. Virchows Arch. path. Anat. 193, 1--92 (1908) Stroer, W. F. It. : ~ber das Zusammentreffen yon I-Iasenscharte mit ernsten Extremit~tenmiBbildung. Erbarzt 7, 101--107 (1939) Virchow, R. : Zeitschrift f. Ethnologic, 30. Jahrg., 1898, as cited by Krueger (1906), as case 65 Wepler, P. : Die sogenannte Fhokomelie. Dtsch. reed. Wschr. 63, 1302--1305 (1937) Werthemann, A. : Die EntwicklungsstSrungender Extremit~ten. In: Handbuch der speziellen pathologischen Anatomie und I-Iistologie, IX/6, p. 113. Berlin-GSttingen-Heidelberg: Springer 1952 Prof. Dr. H. R. Wiedemann Universit~ts-Kinderklinik D-2300 Kiel 1, FrSbelstraBe 15/17 Federal Republic of Germany
