American Journal of Medical Genetics 35:64-68 (1990)
Autosomal Recessive Robinow Syndrome Ahmad S. Teebi Kuwait Medical Genetics Centre, Maternity Hospital and Satellite Genetic Clinics, A m i r i and Farwania Hospitals, Kuwazt ~~~
~
Two brothers of normal first-cousin parents were found to have Robinow syndrome. Their paternal uncle also married a first cousin and had 3 similarly affected children (2 boys, 1 girl). The 2 affected brothers had short stature, mesomelic and acromelic brachymelia, characteristic face with hypertelorism, wide palpebral fissures, midface hypoplasia and large mouth, and hypogenitalism. Parental consanguinity and affected individuals in 2 sibships of common ancestry strongly suggest autosomal recessive inheritance. Similar cases from the literature are briefly reviewed.
CLINICAL REPORTS Patient 1 The propositus (Fig. 1, IV-14) was a 10-year-old boy when examined because of hypoplastic genitalia. He was born normally a t term after a n uneventful pregnancy. Body weight was 3 kg (MI, BL was 48 cm ( - 2SD), and OFC was 35 cm (M). The infant was noted t o have hypertelorism and small genitalia. During the first few years of life his psychomotor development was normal, but compared to his sibs he was short. He had frequent upper respiratory infections in the first 2 years (8-10iyea1-1, which became less frequent afterwards. On examination he had disproportionate short stature with height 124 cm (-ZSD), span KEY WORDS: fetal face, hypoplastic geni115 cm, UBSiLBS ratio 1.5/1. Weight was 27.5 kg (M) talia, mesomelic brachymelia, and OFC was 53 cm (MI. His clinical manifestations short stature (Fig. 2A,B) included a relatively large head with frontal bossing; prominent eyes with wide palpebral fissures and normal vision; apparent hypertelorism (measurements not available); midface hypoplasia with short upINTRODUCTION turned nose, broad nasal bridge, long philtrum, trianguIn their original report, Robinow et al. [1969] de- lar mouth, gingival hypertrophy, maloccluded teeth scribed 9 individuals in a large family with a distinct with widely spaced upper incisors and crowded lower autosomal dominant syndrome transmitted over 6 gen- teeth; narrow palate; relative micrognathia and promierations. Manifestations included mesomelic short stat- nent posteriorly angulated ears with incomplete scapha ure, characteristic face, and hypogenitalism. Additional helix development. All limbs were short. The mesomelic patients were described by Pfeiffer and Muller [1971], shortness appears more marked in the upper limbs. The Wadlington et al. [1973], Vera-Roman [1973], See1et al. hands and feet were broad and stubby. There was [1974], Schinzel et al. [1974], Seemanova et al. [1974], clinodactyly of the 5th fingers and bilateral single inGellis et al. [1975], Hanssler and Schwanitz [1975], complete palmar creases, chest asymmetry, pectus carKelly et al. [19751, Giedion et al. D9751, Wadia et a]. inatum, micropenis with redundant skin and normal [1978], Portnoy [1979], Marni et al. [1980], Petit et al. scrotum and descended testes. The other organs were [1980], Ziska et al. [19811,Shprintzen et al. [19821, Val- unremarkable. l6e et al. [19821, Khayat et al. [19831, Menon et al. Radiographs showed a normal skull with no sign of [1983], Rodriguez-Costa et al. 119841,Bain et al. [19861, increased intracranial pressure, normal vertebrae (Fig. and Butler and Wadlington [1987]. These reports in- 2C) and ribs and normal pelvis but with deepened sciatic cluded both the re1atively “common,” well-documented, notches. There was mesomelic brachymelia of upper autosomal dominant entity and the apparently rare limbs with proportionate shortness of radius and ulna, entity with presumable autosomal recessive inheri- hypoplastic distal ulnar epiphyses and proximal radial tance, Here we report on a large Arab family which epiphyses with slight bowing of the radius and thinning clearly demonstrates autosomal recessive inheritance of the medial part of the distal radial epiphyses (Fig. in Robinow syndrome. 2D). Hand radiographs showed shortness of the 3rd-5th metacarpals with clinodactyly of the 5th fingers. Mesomelic brachymelia was evident also in the lower limbs, gceived for publication December 28, 1988; revision received but the feet appear normal on radiographs. Diaphyseal June 7, 1989. Address reprint requests to Dr. A.S. Teebi, P.O. Box 36660, h a s , bone length ratios are shown in Table I. Bone age was normal. G-banded chromosomes were also normal. 24751. Kuwait. 0 1990 Wiley-Liss, Inc.
Robinow Syndrome
65
I
II
m 1V Fig. 1. Pedigree
Patient 2 The brother of the propositus (Fig. 1, IV-18) was examined at age 6 months. Pregnancy and delivery were normal. Body weight was 3.1 kg (M), BL was 49.5 cm (Mj, and OFC was 35 cm (M).On examination he weighed 5.74 kg ( - 2SD), was 61 cm long ( - 3SD), and had a n OFC of 42.8 cm (M). His clinical manifestations (Fig. 3A) are compared with those of his brother in Table 11. Developmentally he was normal. Radiographs done a t the age of 11months showed similar findings in the skull and limbs but with no evident epiphyseal changes (Fig. 3B). Diaphyseal bone length ratios are compared to patient 1 in Table I. There was evidence of abnormal wedge-shaped vertebrae (T5 and T6) and a butterfly vertebra (T8XFig. 3C) but the ribs were normal. Bone age was normal. Family Data (Fig. 1) Members of the family are Muslim Arabs of Palestinian origin from a small village in the West Bank of the Jordan River. The parents are phenotypically normal first cousins of average height. Father and mother were 31 and 26 years old, respectively, when the propositus was born. They have 6 normal children (3 boys and 3 girls) in addition to male twins who died on the first day of life (details unknown). The father’s brother is married also to a first cousin (living in Jordan) and has 3 similarly affected children (2 boys and a girl) documented by photographs. The eldest is 7 years old and the youngest is 3.
DISCUSSION Robinow syndrome (RS) or “fetal face syndrome” is characterized by shortness of stature and of limbs, distinct facial appearance with hypertelorism, wide palpebral fissures, short upturned nose, and hypoplastic genitalia [Bain et al., 1986; Butler and Wadlington, 19871. The limb shortness is described consistently as mesomelic brachymelia; however, rhizomelic brachymelia, generalized shortness of limbs, or even normal limbs have also been noted [Bain et al., 19861.Vertebral anomalies, first reported by Wadlington et al. [1973], were subsequently found in 21/32 ofRS patients [Butler and Wadlington, 19871. In addition, other skeletal anomalies, namely rib defects, scoliosis and pectus excavatum were less frequently described. Robinow syndrome is genetically heterogeneous. The inheritance is either autosomal dominant or autosomal recessive. The autosomal dominant entity appears relatively common, and the illustrative families hitherto reported [Robinow et al., 1969; Shprintzen et al., 1982; Vallee et al., 1982; Bain et al., 19861 make this mode of inheritance quite certain [McKusick, 19881. Among them, there are examples of male t o male transmission [Shprintzen et al., 1982; Bain et al., 19861. On the other hand, a number of families suggest autosomal recessive inheritance [Wadlington et al., 1973; Seemanova et al., 1974; Wadia et al., 19781. These include 3 affected sib pairs (a male and a female), normal parents, and one instance of parental consanguinity [Wadia et al., 19781. In addition, there are several instances of reported
TABLE I. Diaphyseal Bone Length Ratios in the 2 Sibs With RS
Patient 1 (10 years) Patient 2 (11 months)
Radius Humerus
SD.
Tibia Femur
SD
Humerus Femur
SD
Radius Tibia
SD
0.65
-5
0.75
-3.5
0.63
-3.0
0.54
-4.5
0.67
-4
0.78
-1
0.75
-1.3
0.65
-4
“Standard deviation from mean (MI according to Robinow and Churnlea 11982).
66
Teebi
Robinow Syndrome TABLE 11. Manifestations in the 2 Sibs With Robinow Syndrome Manifestations
Age
Sex Craniofacial Macrocephaly F r o n t a l bossing Proptosis Hypertelorism Wide palpebral fissures Short u p t u r n e d nose Broad nasal bridge Long p h i l t r u m Triangular m o u t h Gingival hyperplasia Dental malocclusion Narrow p a l a t e Relative micrognathia Posteriorly angulated ears with incomplete s c a p h a helix development Acral Acromelic brachymelia Mesomelic brachymelia Clinodactyly of the 5th finger Single incomplete p a l m a r crease
Genital Micropenis Cryptorchidism
Patient 1 (IV-14) 10 years Male
Patient 2
(IV-18) 6 months Male
+ + + + + + + + + -I+ + +
+ + t + + + +-
4
I
+ + + +
+ +
+
+ -
? -
+
I
+ unilateral (right)
Others Disproportionate s h o r t stature Chest deformity
Vertebral changes Epiphyseal changes N o r m a l IQ/DQ Chromosomes
+
+
pectus carinatum
pectus excavatum
+ +
46.XY
+ +
[Onichi, 19761 and unreported autosomal recessive cases (Robinow, personal communication). Bain et al. [19861suggested that the main discriminating factor is the occurrence of multiple rib and vertebral anomalies in the autosomal recessive form together with more severe mesomelic brachymelia. Accordingly, a n attempt has been made to categorize their 2 sporadic cases as being autosomal dominant. The 2 patients described here have all the cardinal manifestations of RS, i.e., the characteristic fetal face with hypertelorism, shortness of limbs and stature, and hypogenitalism; the younger brother had vertebral abnormalities similar to those previously encountered in RS. The brachymelia is predominantly mesomelic. The upper limbs show severe mesomelic shortness far greater than the lower compared to normal standards [Robinow and Chumlea, 19821. The pedigree with 5 affected patients in 2 sibships with normal first-cousin parents who are traced to a
67
common ancestor strongly suggests and illustrates the autosomal recessive inheritance in RS and supports its genetic heterogeneity. The intrafamilial variability encountered in this family with regards to the vertebral anomalies suggests that they are not useful factors in distinguishing the 2 forms, since the propositus did not have vertebral or rib anomalies. On the other hand the suggestion that mesomelic brachymelia is more severe in the recessively inherited cases may be justified. However, I think that a n interfamilial variability also exists among the autosomal recessive and autosomal dominant cases. The overlap between the 2 entities creates nosologic difficulties.
ACKNOWLEDGMENTS I a m grateful to Dr. M. Robinow for encouraging me to write this paper. Also, I thank Dr. A.G. Al-Ansari, FRCR, for radiological report and Mrs. Regina Ratos for typing the manuscript.
REFERENCES Bain MD, Winter RM, Burn J f1986):Robinow syndrome without mesomelic “brachymelia”: A report of five cases. J Med Genet 23:350--354. Butler MG, Wadlington WB (1987):Robinow syndrome: Report of two patients and review of literature. Clin Genet 31:77-85. Gellis SS, Feingold M, Bull M (1975):Picture of the month Fetal face syndrome (Robinow syndrome). Am J Dis Child 129:351-352. Giedion A, Battaglia GF, Bellini F, Fanconi G (1975): A radiological diagnosis of fetal face (Robinow) syndrome imesomelic dwarfism and small genitalia). Helv Paediatr Acta 30:409-423. Hanssler H, Schwanitz G (1975): Report on a variant of the fetal face syndrome with acral dysostosis. Klin Padiatr 187:2774-2777. Kelly TE, Benson R, Temtamy S, Plotnick L, Levin S (1975): The Robinow syndrome: An isolated case with a detailed study of the phenotype. Am J Dis Child 129:383-386. Khayat D, Schiason G, Frija J , SzpirglasH (1983):Robinow’ssyndrome. Arch Fr Pediatr 40:327-330. Marni E, Monafo V, Zanol MG, Pedroni E (1980): The fetal face syndrome or Robinow syndrome. Description of acase. Minerva Pediatr 32:47-52. McKusick VA (1988): “Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes,” 8th Ed. Baltimore: Johns Hopkins University Press, p 665. Menon PS, Thomas S, Mathews AR, Verma IC, Gupta A (1983):Robinow syndrome. Indian Pediatr 20:783-787. Onichi S (1976): Robinow syndrome. Pehatr J 17521-525. Petit P, Fryns J P , Goddeeris P, Perlmutter-Cremer N (1980):The Robinow syndrome. Ann Genet 23:221-223. Pfeiffer RA, Muller H (19711: Ein Komplex multipler Missbildungen bei zwei nicht vcrwandten Kindern. Pediatr Padol 6262-267, Portnoy Y (1979): Robinow syndrome. Clin Pediatr 18:707-708. Robinow M, Chumlea W (1982): Standards for limb bone length ratios in children. Radiology 143:433-436. Robinow M, Silverman FN, Smith HO (1969): A newly recognized dwarfing syndrome. Am J Dis Child 117:645-651. Rodriguez-Costa T, Garcia De Leon R, Cases-Fernandez C, Puchemira A, Perez-Bryan J (1984):Robinow syndrome: Presentation of a case and review of literature. An Esp Pediatr 20x55-61.
Fig. 2. A: Patient 1, characteristic phenotype; B: Hypoplastic genitalia; C: Normal vertebrae; D: Mesomelic shortness of radius and ulna.
68
Teebi
Fig. 3. A: Patient 2, characteristic phenotype with hypoplastic genitalia; B: Mesomelic shortness of radius and ulna; C: Vertebral anomalies (T5 and T6) and a butterfly verbetra (T8).
Schinzel A, Zellweger H, Grella A, Prader A (1974): Fetal face syndrome with acral dysostosis. Helv Paediatr Acta 29:55-60. See1 RE:, Warner I, Passarge E (19743: Robinow’s fetal face-dwarfism syndrome. Monatsschr Kinderheilkd 122:663-664. Seemanova E, Jhasek JE, Sevcikova M, Jodl J, Kreisinger K (1974): Fetal face syndrome with mental retardation. Hum Genet 23:78-81. Shprintzen RJ, Goldberg RB, Saenger P, Sidoti EJ (1982): Male t o male transmission of Robinow’s syndrome. Am J Dis Child 136:594-597 Vera-Roman J M (1973):Robinow dwarfing syndrome accompanied by penile agenesis and hemivertebrae. Am J Dis Child 126:206-208.
Wadia RS, Shirole DB, Dikshit MS (1978): Recessively inherited costovertebral segmentation defect with mesomelia and peculiar facies (Covesdem syndrome). J Med Genet 15:123-127. Wadlington WB, Tucker VL, Schirnke RN (1973): Mesomelic dwarfism with hemivertebrae and small genitalia (the Robinow syndrome). Am J Dis Child 126:202-205. Vall6e L, Van Nerom PY, Ferraz FG, Delecour M, Maroteaux P, Farriaux JP, Fontaine G (1982): Robinow’s syndrome with dominant transmission. Arch Fr Pediatr 39:447-448. Ziska J, Gayer J, Juttnerova V, Balicek P, Tesarova B (1981):Fetal face syndrome. Cesk Pediatr 36:328-330.
Autosomal Recessive Robinow Syndrome Ahmad S. Teebi Kuwait Medical Genetics Centre, Maternity Hospital and Satellite Genetic Clinics, A m i r i and Farwania Hospitals, Kuwazt ~~~
~
Two brothers of normal first-cousin parents were found to have Robinow syndrome. Their paternal uncle also married a first cousin and had 3 similarly affected children (2 boys, 1 girl). The 2 affected brothers had short stature, mesomelic and acromelic brachymelia, characteristic face with hypertelorism, wide palpebral fissures, midface hypoplasia and large mouth, and hypogenitalism. Parental consanguinity and affected individuals in 2 sibships of common ancestry strongly suggest autosomal recessive inheritance. Similar cases from the literature are briefly reviewed.
CLINICAL REPORTS Patient 1 The propositus (Fig. 1, IV-14) was a 10-year-old boy when examined because of hypoplastic genitalia. He was born normally a t term after a n uneventful pregnancy. Body weight was 3 kg (MI, BL was 48 cm ( - 2SD), and OFC was 35 cm (M). The infant was noted t o have hypertelorism and small genitalia. During the first few years of life his psychomotor development was normal, but compared to his sibs he was short. He had frequent upper respiratory infections in the first 2 years (8-10iyea1-1, which became less frequent afterwards. On examination he had disproportionate short stature with height 124 cm (-ZSD), span KEY WORDS: fetal face, hypoplastic geni115 cm, UBSiLBS ratio 1.5/1. Weight was 27.5 kg (M) talia, mesomelic brachymelia, and OFC was 53 cm (MI. His clinical manifestations short stature (Fig. 2A,B) included a relatively large head with frontal bossing; prominent eyes with wide palpebral fissures and normal vision; apparent hypertelorism (measurements not available); midface hypoplasia with short upINTRODUCTION turned nose, broad nasal bridge, long philtrum, trianguIn their original report, Robinow et al. [1969] de- lar mouth, gingival hypertrophy, maloccluded teeth scribed 9 individuals in a large family with a distinct with widely spaced upper incisors and crowded lower autosomal dominant syndrome transmitted over 6 gen- teeth; narrow palate; relative micrognathia and promierations. Manifestations included mesomelic short stat- nent posteriorly angulated ears with incomplete scapha ure, characteristic face, and hypogenitalism. Additional helix development. All limbs were short. The mesomelic patients were described by Pfeiffer and Muller [1971], shortness appears more marked in the upper limbs. The Wadlington et al. [1973], Vera-Roman [1973], See1et al. hands and feet were broad and stubby. There was [1974], Schinzel et al. [1974], Seemanova et al. [1974], clinodactyly of the 5th fingers and bilateral single inGellis et al. [1975], Hanssler and Schwanitz [1975], complete palmar creases, chest asymmetry, pectus carKelly et al. [19751, Giedion et al. D9751, Wadia et a]. inatum, micropenis with redundant skin and normal [1978], Portnoy [1979], Marni et al. [1980], Petit et al. scrotum and descended testes. The other organs were [1980], Ziska et al. [19811,Shprintzen et al. [19821, Val- unremarkable. l6e et al. [19821, Khayat et al. [19831, Menon et al. Radiographs showed a normal skull with no sign of [1983], Rodriguez-Costa et al. 119841,Bain et al. [19861, increased intracranial pressure, normal vertebrae (Fig. and Butler and Wadlington [1987]. These reports in- 2C) and ribs and normal pelvis but with deepened sciatic cluded both the re1atively “common,” well-documented, notches. There was mesomelic brachymelia of upper autosomal dominant entity and the apparently rare limbs with proportionate shortness of radius and ulna, entity with presumable autosomal recessive inheri- hypoplastic distal ulnar epiphyses and proximal radial tance, Here we report on a large Arab family which epiphyses with slight bowing of the radius and thinning clearly demonstrates autosomal recessive inheritance of the medial part of the distal radial epiphyses (Fig. in Robinow syndrome. 2D). Hand radiographs showed shortness of the 3rd-5th metacarpals with clinodactyly of the 5th fingers. Mesomelic brachymelia was evident also in the lower limbs, gceived for publication December 28, 1988; revision received but the feet appear normal on radiographs. Diaphyseal June 7, 1989. Address reprint requests to Dr. A.S. Teebi, P.O. Box 36660, h a s , bone length ratios are shown in Table I. Bone age was normal. G-banded chromosomes were also normal. 24751. Kuwait. 0 1990 Wiley-Liss, Inc.
Robinow Syndrome
65
I
II
m 1V Fig. 1. Pedigree
Patient 2 The brother of the propositus (Fig. 1, IV-18) was examined at age 6 months. Pregnancy and delivery were normal. Body weight was 3.1 kg (M), BL was 49.5 cm (Mj, and OFC was 35 cm (M).On examination he weighed 5.74 kg ( - 2SD), was 61 cm long ( - 3SD), and had a n OFC of 42.8 cm (M). His clinical manifestations (Fig. 3A) are compared with those of his brother in Table 11. Developmentally he was normal. Radiographs done a t the age of 11months showed similar findings in the skull and limbs but with no evident epiphyseal changes (Fig. 3B). Diaphyseal bone length ratios are compared to patient 1 in Table I. There was evidence of abnormal wedge-shaped vertebrae (T5 and T6) and a butterfly vertebra (T8XFig. 3C) but the ribs were normal. Bone age was normal. Family Data (Fig. 1) Members of the family are Muslim Arabs of Palestinian origin from a small village in the West Bank of the Jordan River. The parents are phenotypically normal first cousins of average height. Father and mother were 31 and 26 years old, respectively, when the propositus was born. They have 6 normal children (3 boys and 3 girls) in addition to male twins who died on the first day of life (details unknown). The father’s brother is married also to a first cousin (living in Jordan) and has 3 similarly affected children (2 boys and a girl) documented by photographs. The eldest is 7 years old and the youngest is 3.
DISCUSSION Robinow syndrome (RS) or “fetal face syndrome” is characterized by shortness of stature and of limbs, distinct facial appearance with hypertelorism, wide palpebral fissures, short upturned nose, and hypoplastic genitalia [Bain et al., 1986; Butler and Wadlington, 19871. The limb shortness is described consistently as mesomelic brachymelia; however, rhizomelic brachymelia, generalized shortness of limbs, or even normal limbs have also been noted [Bain et al., 19861.Vertebral anomalies, first reported by Wadlington et al. [1973], were subsequently found in 21/32 ofRS patients [Butler and Wadlington, 19871. In addition, other skeletal anomalies, namely rib defects, scoliosis and pectus excavatum were less frequently described. Robinow syndrome is genetically heterogeneous. The inheritance is either autosomal dominant or autosomal recessive. The autosomal dominant entity appears relatively common, and the illustrative families hitherto reported [Robinow et al., 1969; Shprintzen et al., 1982; Vallee et al., 1982; Bain et al., 19861 make this mode of inheritance quite certain [McKusick, 19881. Among them, there are examples of male t o male transmission [Shprintzen et al., 1982; Bain et al., 19861. On the other hand, a number of families suggest autosomal recessive inheritance [Wadlington et al., 1973; Seemanova et al., 1974; Wadia et al., 19781. These include 3 affected sib pairs (a male and a female), normal parents, and one instance of parental consanguinity [Wadia et al., 19781. In addition, there are several instances of reported
TABLE I. Diaphyseal Bone Length Ratios in the 2 Sibs With RS
Patient 1 (10 years) Patient 2 (11 months)
Radius Humerus
SD.
Tibia Femur
SD
Humerus Femur
SD
Radius Tibia
SD
0.65
-5
0.75
-3.5
0.63
-3.0
0.54
-4.5
0.67
-4
0.78
-1
0.75
-1.3
0.65
-4
“Standard deviation from mean (MI according to Robinow and Churnlea 11982).
66
Teebi
Robinow Syndrome TABLE 11. Manifestations in the 2 Sibs With Robinow Syndrome Manifestations
Age
Sex Craniofacial Macrocephaly F r o n t a l bossing Proptosis Hypertelorism Wide palpebral fissures Short u p t u r n e d nose Broad nasal bridge Long p h i l t r u m Triangular m o u t h Gingival hyperplasia Dental malocclusion Narrow p a l a t e Relative micrognathia Posteriorly angulated ears with incomplete s c a p h a helix development Acral Acromelic brachymelia Mesomelic brachymelia Clinodactyly of the 5th finger Single incomplete p a l m a r crease
Genital Micropenis Cryptorchidism
Patient 1 (IV-14) 10 years Male
Patient 2
(IV-18) 6 months Male
+ + + + + + + + + -I+ + +
+ + t + + + +-
4
I
+ + + +
+ +
+
+ -
? -
+
I
+ unilateral (right)
Others Disproportionate s h o r t stature Chest deformity
Vertebral changes Epiphyseal changes N o r m a l IQ/DQ Chromosomes
+
+
pectus carinatum
pectus excavatum
+ +
46.XY
+ +
[Onichi, 19761 and unreported autosomal recessive cases (Robinow, personal communication). Bain et al. [19861suggested that the main discriminating factor is the occurrence of multiple rib and vertebral anomalies in the autosomal recessive form together with more severe mesomelic brachymelia. Accordingly, a n attempt has been made to categorize their 2 sporadic cases as being autosomal dominant. The 2 patients described here have all the cardinal manifestations of RS, i.e., the characteristic fetal face with hypertelorism, shortness of limbs and stature, and hypogenitalism; the younger brother had vertebral abnormalities similar to those previously encountered in RS. The brachymelia is predominantly mesomelic. The upper limbs show severe mesomelic shortness far greater than the lower compared to normal standards [Robinow and Chumlea, 19821. The pedigree with 5 affected patients in 2 sibships with normal first-cousin parents who are traced to a
67
common ancestor strongly suggests and illustrates the autosomal recessive inheritance in RS and supports its genetic heterogeneity. The intrafamilial variability encountered in this family with regards to the vertebral anomalies suggests that they are not useful factors in distinguishing the 2 forms, since the propositus did not have vertebral or rib anomalies. On the other hand the suggestion that mesomelic brachymelia is more severe in the recessively inherited cases may be justified. However, I think that a n interfamilial variability also exists among the autosomal recessive and autosomal dominant cases. The overlap between the 2 entities creates nosologic difficulties.
ACKNOWLEDGMENTS I a m grateful to Dr. M. Robinow for encouraging me to write this paper. Also, I thank Dr. A.G. Al-Ansari, FRCR, for radiological report and Mrs. Regina Ratos for typing the manuscript.
REFERENCES Bain MD, Winter RM, Burn J f1986):Robinow syndrome without mesomelic “brachymelia”: A report of five cases. J Med Genet 23:350--354. Butler MG, Wadlington WB (1987):Robinow syndrome: Report of two patients and review of literature. Clin Genet 31:77-85. Gellis SS, Feingold M, Bull M (1975):Picture of the month Fetal face syndrome (Robinow syndrome). Am J Dis Child 129:351-352. Giedion A, Battaglia GF, Bellini F, Fanconi G (1975): A radiological diagnosis of fetal face (Robinow) syndrome imesomelic dwarfism and small genitalia). Helv Paediatr Acta 30:409-423. Hanssler H, Schwanitz G (1975): Report on a variant of the fetal face syndrome with acral dysostosis. Klin Padiatr 187:2774-2777. Kelly TE, Benson R, Temtamy S, Plotnick L, Levin S (1975): The Robinow syndrome: An isolated case with a detailed study of the phenotype. Am J Dis Child 129:383-386. Khayat D, Schiason G, Frija J , SzpirglasH (1983):Robinow’ssyndrome. Arch Fr Pediatr 40:327-330. Marni E, Monafo V, Zanol MG, Pedroni E (1980): The fetal face syndrome or Robinow syndrome. Description of acase. Minerva Pediatr 32:47-52. McKusick VA (1988): “Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes,” 8th Ed. Baltimore: Johns Hopkins University Press, p 665. Menon PS, Thomas S, Mathews AR, Verma IC, Gupta A (1983):Robinow syndrome. Indian Pediatr 20:783-787. Onichi S (1976): Robinow syndrome. Pehatr J 17521-525. Petit P, Fryns J P , Goddeeris P, Perlmutter-Cremer N (1980):The Robinow syndrome. Ann Genet 23:221-223. Pfeiffer RA, Muller H (19711: Ein Komplex multipler Missbildungen bei zwei nicht vcrwandten Kindern. Pediatr Padol 6262-267, Portnoy Y (1979): Robinow syndrome. Clin Pediatr 18:707-708. Robinow M, Chumlea W (1982): Standards for limb bone length ratios in children. Radiology 143:433-436. Robinow M, Silverman FN, Smith HO (1969): A newly recognized dwarfing syndrome. Am J Dis Child 117:645-651. Rodriguez-Costa T, Garcia De Leon R, Cases-Fernandez C, Puchemira A, Perez-Bryan J (1984):Robinow syndrome: Presentation of a case and review of literature. An Esp Pediatr 20x55-61.
Fig. 2. A: Patient 1, characteristic phenotype; B: Hypoplastic genitalia; C: Normal vertebrae; D: Mesomelic shortness of radius and ulna.
68
Teebi
Fig. 3. A: Patient 2, characteristic phenotype with hypoplastic genitalia; B: Mesomelic shortness of radius and ulna; C: Vertebral anomalies (T5 and T6) and a butterfly verbetra (T8).
Schinzel A, Zellweger H, Grella A, Prader A (1974): Fetal face syndrome with acral dysostosis. Helv Paediatr Acta 29:55-60. See1 RE:, Warner I, Passarge E (19743: Robinow’s fetal face-dwarfism syndrome. Monatsschr Kinderheilkd 122:663-664. Seemanova E, Jhasek JE, Sevcikova M, Jodl J, Kreisinger K (1974): Fetal face syndrome with mental retardation. Hum Genet 23:78-81. Shprintzen RJ, Goldberg RB, Saenger P, Sidoti EJ (1982): Male t o male transmission of Robinow’s syndrome. Am J Dis Child 136:594-597 Vera-Roman J M (1973):Robinow dwarfing syndrome accompanied by penile agenesis and hemivertebrae. Am J Dis Child 126:206-208.
Wadia RS, Shirole DB, Dikshit MS (1978): Recessively inherited costovertebral segmentation defect with mesomelia and peculiar facies (Covesdem syndrome). J Med Genet 15:123-127. Wadlington WB, Tucker VL, Schirnke RN (1973): Mesomelic dwarfism with hemivertebrae and small genitalia (the Robinow syndrome). Am J Dis Child 126:202-205. Vall6e L, Van Nerom PY, Ferraz FG, Delecour M, Maroteaux P, Farriaux JP, Fontaine G (1982): Robinow’s syndrome with dominant transmission. Arch Fr Pediatr 39:447-448. Ziska J, Gayer J, Juttnerova V, Balicek P, Tesarova B (1981):Fetal face syndrome. Cesk Pediatr 36:328-330.
