American Journal of Medical Genetics 41:438-443 (1991)
New Form of Postaxial Acrofacial Dysostosis? Raanan Arens, Brian Reichmsn, Mariassa Bat-MiriamKatznelson, and Richard M. Goodman Department of Pediatrics (R.A) and Division of Neonatology (B.R), Chaim Sheba Medical Center, Tel-Hashomer; Institute of Medical Genetics (M.B.K,R.M.G), Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
We report on a 2-month-oldSephardic Jewish girl with bilateral and symmetrical deficiency of the fifth digital rays of all 4 limbs, combined with severe deformations and other malformations of the limbs. These findings were associated with orofacial malformations,as well as with visceral anomalies differing from those found in other postaxial deficiency syndromes. Parents were closely consanguineous. We assume this patient represents a new form of postaxial acrofacial dysostosis. KEY WORDS: birth defects, postaxial deficiency syndromes, limb deficiency INTRODUCTION Postaxial limb deficiencies appear in several disorders; however, bilateral symmetrical deficiency of the fifth rays of the upper and lower limbs is quite unique and was reported only sporadically. In early reports by Birch-Jensen, [19491, Genke (19691, Rosselli and Gulienetti [19601,and Wiedemann L19731, other malformations were observed in addition t o the deficiency of the fifth digital rays of all four limbs, especially orofacia1 malformations. Later, Miller et al. [19791delineated the postaxial acrofacial dysostosis syndrome which included absence of the fifth digital rays of all 4 limbs associated with ulnar hypoplasia or radial-ulnar synostosis, cup-shaped ears, coloboma of eyelids, micrognathia, cleft lip and cleft palate, and accessory nipples. Recently, we evaluated a child with the previous undescribed findings of bilateral symmetrical deficiency of the fifth digital rays of all 4 limbs and other abnormalities, which together appear to be anew clinical entity in the group of postaxial acrofacial dysostoses. CLINICAL REPORT The 2-month-oldgirl was the offspring of healthy parents who are uncle and niece. At the time of the child's Received for publication October 4,1590; revision received April 22, 1591. Address reprint requests to Raanan Arens, M.D., Department of Pediatrics, Chaim Sheba Medical Center, Tel Hashomer, 52621 Israel.
0 1991 Wiley-Liss, Inc.
birth, the mother was 25 years old and the father 28. This was the mother's fourth pregnancy and third delivery. The child was delivered at the end of an uneventful 41-week pregnancy. Weight was 2,370 g (3rd centile). Multiple congenital anomalies included micrognathia; hypertelorism; short, downward slanting palpebral fissures; apparently low-set ears, with narrow external auditory meati; small nose with flat nasal bridge and hypoplasia of the nares; small mouth with downturned corners (Fig. 1);and tetramelic absence of the fifth digital ray with cubitus valqus deformation of the upper limbs. There was bilateral camptodactyly, type 3 syndactyly, and an additional rudimentary finger between 3 and 4 (Fig. 2A,B). The infant also had bilateral congenital hip dislocation, club foot deformities, absence of the fifth digits, absence of distal phalanges of the second and third toes (Fig. 3A,B), a short neck, a small chest, a sacral sinus, and a cardiac murmur 216 on the left sternal border. Radiographs of the hands showed bilateral absence of the fifth metacarpals (Fig. 2C,D);radiographs of the feet showed bilateral absence of the fifth metatarsals and distal phalanges of toes 2 to 3 (Fig. 3 0 . An echocardiogram showed a moderate size patent ductus arteriosus, which remained open during hospitalization; abdominal ultrasonography documented mild hydronephrosis of the right kidney. The most outstanding dermatoglyphic change noted was the high number of arches on both digits and toes and the longitudinal alignment of ridges on the palms (Fig. 4). The former observation represents underdevelopment of the digital pads during embryogenesis. Banded chromosome analysis of peripheral lymphocyte culture were normal (46,XX).During hospitalization, the child showed increasing difficulty in feeding, requiring use of a gastric tube. The radiological examination demonstrated a good swallowing mechanism and a mild gastro-esophageal reflux, but decreased intestinal motility. The child died at age 2 months with a clinical picture of intestinal obstruction. Permission for a post mortem examination could not be obtained.
DISCUSSION The postaxial acrofacial dysostoses are a group of genetic disorders associated mainly with postaxial limb deficiencies. However, postaxial acrofacial dysostosis is the only one known with bilateral symmetrical limb deficiency of the fifth digital rays of the upper and lower
Postaxial Acrofacial Dysostosis
439
Fig. 1. (A) proposita at birth, (B)deformed opening of the external meati, and (C)proposita at age 2 months.
limbs. This phenotype also includes orofacial and ear malformation distinguishing it from the others noted in Table I. Postaxial limb deficiencies associated with orofacial and ear malformations were first noted by BirchJensen [19491. Later Rosselli and Gulienetti [19601 reported on a family with 4 affected sibs. Wiedemann 119731 reported on a 3-year-old who, in addition, was severely retarded. He suggested for this form the term “malformation retardation syndrome.” Miller et al. [19791 delineated the postaxial acrofacial dysostosis “syndrome.” They described 2 patients and reviewed 3 others previously reported by Smith et al. [19751and one reported by Gen6e [19691. The main clinical findings in
these patients are bilateral symmetrical postaxial limb deficiency of the fifth digital ray of all 4 limbs, ulnar hypoplasia or synostosis, cup shaped ears, coloboma of eyelids, micrognathia, cleft lip or cleft palate, and accessory nipples. Since then 12 patients affected with this disorder have been described [Fineman, 1981;Meinecke and Wiedemann, 1987;Opitz and Stickler, 1987;Donnai et a]., 1987; Hauss-Albert, 1988; Fryns and Van den Berghe, 1988; Chrzanowska et al., 1989; Richieri-Costa and Guion-Almeida, 1989; Richards, 1987; Barbuti et al., 19891. Some phenotypic variability has been documented by Opitz and Stickler and Fineman who reported the occurrence of this disorder in two pairs of sibs.
440
Arensetal.
Fig. 2. (A and B) right and left hand showing camptodactyly, syndactyly, and the rudimentary finger between 3 and 4,(C and D) roentgenogram of right and left hands showing absence of fifth metacarpal bones.
Donnai et al. [ 19871summarized the clinical manifestations of 10 affected patients with postaxial acrofacial dysostosis. They found some variability in the orofacial and limb malformations. However, some findings are constant: absence of the fifth digital rays of both upper and lower limbs appears in all of the patients, as well as micrognathia, malar hypoplasia, and ectropion of the eyelids. Cleft palate and cup-shaped ears appear in 90% of the patients, ulnar hypoplasia or radial-ulnar synostosis in 70%,and accessory nipples in 50%.Other abnor-
malities were less constant. Recently, Rodriguez et al. [19901 reported on a new acrofacial dysostosis syndrome. They reported 3 sibs who died neonatally due to respiratory complications. Their manifestations consisted mainly of mandibulofacial dysostosis, predominantly preaxial limb deficiencies and to a lesser extent postaxial limb anomalies and shoulder or pelvic girdle hypoplasia. In addition, cardiac and CNS anomalies occurred in those infants. We conclude that our patient represents a new type of
Postaxial Acrofacial Dysostosis
Fig. 3. (A and B) bilateral club-foot deformity with bilateral absence of fifth digital rays and distal phalanges of second and third toes, (C) X-ray film of feet showing bilateral absence of fifth metatarsal bones.
Fig. 4. Diagram of proposita’s abnormal dermatoglyphics (see text).
441
Present disorder
Rodriquez acrofacial dysostosis syndrome
FFU syndrome Femur-fibula-ulnar syndrome Schinzel syndrome
Brachmann-de Lange syndrome
Weyers oligodactyly syndrome
Robin sequence and oligodactyly
Miller Postaxial acrofacial dysostosis syndrome
+ -
Rare
+ + +
+
+
+
c
+
+
+
+
+
+
Postaxial symmetrical Postaxial Postaxial deficiency of fibular the fifth ulnar deficiency deficiency digital ray
Genua valga, CDH, clubfoot, deficiencies of phalanges, syndactyly type 3, camptodactyly, additional rudimentary finger
Preaxial limb deficiency, shoulder/ pelvic girdle hypoplasia phocomelia, vertebravrib anomalies
Ulnar hypoplasia, reduced sternal segments Phocomelia, micromelia, oligodactyly, syndactyly, clinodactyly, ulnarlradial hypoplasia, proximal thumb insertion
Preaxial reduction anomalies
Other skeletal malformations Ulnar-hypoplasia, radial-ulnar synostosis, syndactyly, proximal thumb insertion, extra-vertebrae and rib
Microgentilism, undescendant testes, delayed puberty, obesity, anal atresia Mandibulofacial dys- Cardiac anomalies, ostosis, microCNS malformagnathia, low-set tions ears, downward slanting palpable fissure, cleft palate Low-set ears, narrow Congenital heart disease, hydroexternal auditory nephrosis, demeati, hypertelorcreased intestinal ism, downward motility, sacral slanting of palsinus pebral fissures, flat nasal bridge, hypoplastic nares, micrognathia, small mouth with downward slanting corners
Orofacial Visceral malformations malformations ~Congenital heart Cup-shaped ears, disease, accessory downward slanting of eyelids, colnipples, mental retardation reported oboma, ectropion of eyelids, cleft lip/ palate, micrognathia, malar hypoplasia Cleft palate, micrognathia retroglossia, narrow face, small chin Cleft lip/palate, hy- Spleen and kidney malformations, anpoplastic maxilla, tecubital pterygia malar hypoplasia Mental retardation, Long eye-lashes, hirsutism, cutis Small nose, antemarmurata, gasverted nostrils, trointestinal high palate, mianomalies, Cardiocrognathia, microvascular anomabrachycephaly lies
TABLE I. Postaxial Deficiency Syndromes
Autosomal recessive?
Autosomal recessive
Autosomal dominant
Unknown
Autosomal dominant? Autosoma1 recessive?
Autosomal recessive
Unknown
Inheritance Autosomal dominant? Autosoma1 recessive?
Postaxial Acrofacial Dysostosis
postaxial acrofacial dysostosis. The main traits are severe limb malformations including bilateral symmetrical deficiency of the fifth digital rays of all four limbs, syndactyly type 3, an additional rudimentary finger between 3 and 4, and distal deficiencies of the phalanges. Genua valga, congenital dislocation of the hip, and club foot deformities were also apparent. The main facial changes were micrognathia, hypertelorism with downward slant of palpebral fissures, apparently lowset ears with narrow of the external auditory meati, a flat nasal bridge with hypoplastic nares, and a small mouth with downward slanting corners. Visceral anomalies included congenital heart disease (patent ductus arteriosus), hydronephrosis, and decrease in intestinal motility. The only other postaxial deficiency syndrome with bilateral deficiency of the fifth digital rays of all 4 limbs associated with orofacial and visceral anomalies is the postaxial acrofacial dysostosis syndrome delineated by Miller. Our patient appears to present a new form of postaxial acrofacial dysostosis. The hand and foot anomalies of our patient are more severe and the orofacial and ear anomalies are completely different. On the other hand, our patient lacks some key manifestations of other postaxial acrofacial dysostoses, such as cleft palate, cup-shaped ears, coloboma and ectropion of the eyelids, and ulnar hypoplasia or radial ulnar synostosis. Close parental consanguinity associated with this disorder suggests an autosomal recessive inheritance. As more cases of this disorder are reported, clarity regarding the matter of inheritance and heterogeneity will become apparent-a point crucial in genetic counseling.
REFERENCES Barbuti D, Drazi C, Reale A, Paradisi C (1989): Postaxial acrofacial dysostosis or Miller syndrome-A case report. Eur J Pediatr 148:445-446.
443
BirchJensen A (1949): Congenital deformities of the upper extremities. Domus Biol Hered Humanae Univ Hafiensis. Odense and Copenhagen: Ejnar Munskgaards, Beobachtung 19206. Chrzanowska KH, Fryns JP, Krajewska-Walesek M, Wisniewski L, Van den Benghe H (1989): Phenotype variability in the Miller acrofacial dysostosis syndrome. Report of two further patients. Clin Genet 35157-160. Donnai D, Hughes HE, Winter RM (1987):Postaxial acrofacial dysostosis (Miller) syndrome. J Med Genet 24:422-425. Fineman RM (1981):Recurrence of the postaxial acrofacial dysostosis syndrome in a sibship: Implications for genetic counseling. J Pediatr 98:87-88. Fryns JP, Van den Berghe H (1988):Acrofacial dysostosis with postaxial limb deficiency. Am J Med Genet 29:205-208. Gen6e E (1969):Une forme extensive de dysostose mandibulofaciale.J GBn6t Hum 17:45-52. Hauss-Albert H (1988):Postaxial acrofacial dysostosis syndrome with microcephaly, seizures, and profound mental retardation. Am J Med Genet 31:701-703. Meinecke P, Wiedemann HR (1987): Letter t o the Editor: Robin sequence and oligodactyly in mother and son-Probably a further example of the postaxial acrofacial dysostosis syndrome. Am J Med Genet 27:953-956. Miller M, Fineman R, Smith DW (1979):Postaxial acrofacial dysostosis syndrome. J Pediatr 95970-975. Opitz JM, Stickler GB (1987): Letter to the Editor: The GenBe-Wiedemann syndrome, a n acrofacial dysostosi+Further observation. Am J Med Genet 27:971-975. Richards M (1987):Miller syndrome: Anaesthetic management of postaxial acrofacial dysostosis. Anaesthesia 42:871-874. Richierie-Costa A, Guion-Almeida ML (1989):Postaxial acrofacial dysostosis: Report of a Brazilian patient. Am J Med Genet 33:447-449. Rodriguez JI, Palacios J , Urioste M (1990):New acrofacial dysostosis syndrome in 3 sibs. Am J Med Genet 35:484-489. Rosselli D, Gulienetti R (1960): “Le Malformazioni Associate.” Turin: Edizione Minerva Medica, pp 157-158. Smith DW, Pashayan H, Wildervanck LS (1975):Case Report 28. Syndrome Identification 3:7-13. Wiedemann HR (1973): Mipbildungs-Retardierungs-Syndrommit Fehlen des 5. Strahls a n Handen und Fiipen, Gaumenspalte, dysplastischen Ohren und Augenlidern und radioulnarer Synostose. Klin Padiatr 185181-186.
New Form of Postaxial Acrofacial Dysostosis? Raanan Arens, Brian Reichmsn, Mariassa Bat-MiriamKatznelson, and Richard M. Goodman Department of Pediatrics (R.A) and Division of Neonatology (B.R), Chaim Sheba Medical Center, Tel-Hashomer; Institute of Medical Genetics (M.B.K,R.M.G), Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
We report on a 2-month-oldSephardic Jewish girl with bilateral and symmetrical deficiency of the fifth digital rays of all 4 limbs, combined with severe deformations and other malformations of the limbs. These findings were associated with orofacial malformations,as well as with visceral anomalies differing from those found in other postaxial deficiency syndromes. Parents were closely consanguineous. We assume this patient represents a new form of postaxial acrofacial dysostosis. KEY WORDS: birth defects, postaxial deficiency syndromes, limb deficiency INTRODUCTION Postaxial limb deficiencies appear in several disorders; however, bilateral symmetrical deficiency of the fifth rays of the upper and lower limbs is quite unique and was reported only sporadically. In early reports by Birch-Jensen, [19491, Genke (19691, Rosselli and Gulienetti [19601,and Wiedemann L19731, other malformations were observed in addition t o the deficiency of the fifth digital rays of all four limbs, especially orofacia1 malformations. Later, Miller et al. [19791delineated the postaxial acrofacial dysostosis syndrome which included absence of the fifth digital rays of all 4 limbs associated with ulnar hypoplasia or radial-ulnar synostosis, cup-shaped ears, coloboma of eyelids, micrognathia, cleft lip and cleft palate, and accessory nipples. Recently, we evaluated a child with the previous undescribed findings of bilateral symmetrical deficiency of the fifth digital rays of all 4 limbs and other abnormalities, which together appear to be anew clinical entity in the group of postaxial acrofacial dysostoses. CLINICAL REPORT The 2-month-oldgirl was the offspring of healthy parents who are uncle and niece. At the time of the child's Received for publication October 4,1590; revision received April 22, 1591. Address reprint requests to Raanan Arens, M.D., Department of Pediatrics, Chaim Sheba Medical Center, Tel Hashomer, 52621 Israel.
0 1991 Wiley-Liss, Inc.
birth, the mother was 25 years old and the father 28. This was the mother's fourth pregnancy and third delivery. The child was delivered at the end of an uneventful 41-week pregnancy. Weight was 2,370 g (3rd centile). Multiple congenital anomalies included micrognathia; hypertelorism; short, downward slanting palpebral fissures; apparently low-set ears, with narrow external auditory meati; small nose with flat nasal bridge and hypoplasia of the nares; small mouth with downturned corners (Fig. 1);and tetramelic absence of the fifth digital ray with cubitus valqus deformation of the upper limbs. There was bilateral camptodactyly, type 3 syndactyly, and an additional rudimentary finger between 3 and 4 (Fig. 2A,B). The infant also had bilateral congenital hip dislocation, club foot deformities, absence of the fifth digits, absence of distal phalanges of the second and third toes (Fig. 3A,B), a short neck, a small chest, a sacral sinus, and a cardiac murmur 216 on the left sternal border. Radiographs of the hands showed bilateral absence of the fifth metacarpals (Fig. 2C,D);radiographs of the feet showed bilateral absence of the fifth metatarsals and distal phalanges of toes 2 to 3 (Fig. 3 0 . An echocardiogram showed a moderate size patent ductus arteriosus, which remained open during hospitalization; abdominal ultrasonography documented mild hydronephrosis of the right kidney. The most outstanding dermatoglyphic change noted was the high number of arches on both digits and toes and the longitudinal alignment of ridges on the palms (Fig. 4). The former observation represents underdevelopment of the digital pads during embryogenesis. Banded chromosome analysis of peripheral lymphocyte culture were normal (46,XX).During hospitalization, the child showed increasing difficulty in feeding, requiring use of a gastric tube. The radiological examination demonstrated a good swallowing mechanism and a mild gastro-esophageal reflux, but decreased intestinal motility. The child died at age 2 months with a clinical picture of intestinal obstruction. Permission for a post mortem examination could not be obtained.
DISCUSSION The postaxial acrofacial dysostoses are a group of genetic disorders associated mainly with postaxial limb deficiencies. However, postaxial acrofacial dysostosis is the only one known with bilateral symmetrical limb deficiency of the fifth digital rays of the upper and lower
Postaxial Acrofacial Dysostosis
439
Fig. 1. (A) proposita at birth, (B)deformed opening of the external meati, and (C)proposita at age 2 months.
limbs. This phenotype also includes orofacial and ear malformation distinguishing it from the others noted in Table I. Postaxial limb deficiencies associated with orofacial and ear malformations were first noted by BirchJensen [19491. Later Rosselli and Gulienetti [19601 reported on a family with 4 affected sibs. Wiedemann 119731 reported on a 3-year-old who, in addition, was severely retarded. He suggested for this form the term “malformation retardation syndrome.” Miller et al. [19791 delineated the postaxial acrofacial dysostosis “syndrome.” They described 2 patients and reviewed 3 others previously reported by Smith et al. [19751and one reported by Gen6e [19691. The main clinical findings in
these patients are bilateral symmetrical postaxial limb deficiency of the fifth digital ray of all 4 limbs, ulnar hypoplasia or synostosis, cup shaped ears, coloboma of eyelids, micrognathia, cleft lip or cleft palate, and accessory nipples. Since then 12 patients affected with this disorder have been described [Fineman, 1981;Meinecke and Wiedemann, 1987;Opitz and Stickler, 1987;Donnai et a]., 1987; Hauss-Albert, 1988; Fryns and Van den Berghe, 1988; Chrzanowska et al., 1989; Richieri-Costa and Guion-Almeida, 1989; Richards, 1987; Barbuti et al., 19891. Some phenotypic variability has been documented by Opitz and Stickler and Fineman who reported the occurrence of this disorder in two pairs of sibs.
440
Arensetal.
Fig. 2. (A and B) right and left hand showing camptodactyly, syndactyly, and the rudimentary finger between 3 and 4,(C and D) roentgenogram of right and left hands showing absence of fifth metacarpal bones.
Donnai et al. [ 19871summarized the clinical manifestations of 10 affected patients with postaxial acrofacial dysostosis. They found some variability in the orofacial and limb malformations. However, some findings are constant: absence of the fifth digital rays of both upper and lower limbs appears in all of the patients, as well as micrognathia, malar hypoplasia, and ectropion of the eyelids. Cleft palate and cup-shaped ears appear in 90% of the patients, ulnar hypoplasia or radial-ulnar synostosis in 70%,and accessory nipples in 50%.Other abnor-
malities were less constant. Recently, Rodriguez et al. [19901 reported on a new acrofacial dysostosis syndrome. They reported 3 sibs who died neonatally due to respiratory complications. Their manifestations consisted mainly of mandibulofacial dysostosis, predominantly preaxial limb deficiencies and to a lesser extent postaxial limb anomalies and shoulder or pelvic girdle hypoplasia. In addition, cardiac and CNS anomalies occurred in those infants. We conclude that our patient represents a new type of
Postaxial Acrofacial Dysostosis
Fig. 3. (A and B) bilateral club-foot deformity with bilateral absence of fifth digital rays and distal phalanges of second and third toes, (C) X-ray film of feet showing bilateral absence of fifth metatarsal bones.
Fig. 4. Diagram of proposita’s abnormal dermatoglyphics (see text).
441
Present disorder
Rodriquez acrofacial dysostosis syndrome
FFU syndrome Femur-fibula-ulnar syndrome Schinzel syndrome
Brachmann-de Lange syndrome
Weyers oligodactyly syndrome
Robin sequence and oligodactyly
Miller Postaxial acrofacial dysostosis syndrome
+ -
Rare
+ + +
+
+
+
c
+
+
+
+
+
+
Postaxial symmetrical Postaxial Postaxial deficiency of fibular the fifth ulnar deficiency deficiency digital ray
Genua valga, CDH, clubfoot, deficiencies of phalanges, syndactyly type 3, camptodactyly, additional rudimentary finger
Preaxial limb deficiency, shoulder/ pelvic girdle hypoplasia phocomelia, vertebravrib anomalies
Ulnar hypoplasia, reduced sternal segments Phocomelia, micromelia, oligodactyly, syndactyly, clinodactyly, ulnarlradial hypoplasia, proximal thumb insertion
Preaxial reduction anomalies
Other skeletal malformations Ulnar-hypoplasia, radial-ulnar synostosis, syndactyly, proximal thumb insertion, extra-vertebrae and rib
Microgentilism, undescendant testes, delayed puberty, obesity, anal atresia Mandibulofacial dys- Cardiac anomalies, ostosis, microCNS malformagnathia, low-set tions ears, downward slanting palpable fissure, cleft palate Low-set ears, narrow Congenital heart disease, hydroexternal auditory nephrosis, demeati, hypertelorcreased intestinal ism, downward motility, sacral slanting of palsinus pebral fissures, flat nasal bridge, hypoplastic nares, micrognathia, small mouth with downward slanting corners
Orofacial Visceral malformations malformations ~Congenital heart Cup-shaped ears, disease, accessory downward slanting of eyelids, colnipples, mental retardation reported oboma, ectropion of eyelids, cleft lip/ palate, micrognathia, malar hypoplasia Cleft palate, micrognathia retroglossia, narrow face, small chin Cleft lip/palate, hy- Spleen and kidney malformations, anpoplastic maxilla, tecubital pterygia malar hypoplasia Mental retardation, Long eye-lashes, hirsutism, cutis Small nose, antemarmurata, gasverted nostrils, trointestinal high palate, mianomalies, Cardiocrognathia, microvascular anomabrachycephaly lies
TABLE I. Postaxial Deficiency Syndromes
Autosomal recessive?
Autosomal recessive
Autosomal dominant
Unknown
Autosomal dominant? Autosoma1 recessive?
Autosomal recessive
Unknown
Inheritance Autosomal dominant? Autosoma1 recessive?
Postaxial Acrofacial Dysostosis
postaxial acrofacial dysostosis. The main traits are severe limb malformations including bilateral symmetrical deficiency of the fifth digital rays of all four limbs, syndactyly type 3, an additional rudimentary finger between 3 and 4, and distal deficiencies of the phalanges. Genua valga, congenital dislocation of the hip, and club foot deformities were also apparent. The main facial changes were micrognathia, hypertelorism with downward slant of palpebral fissures, apparently lowset ears with narrow of the external auditory meati, a flat nasal bridge with hypoplastic nares, and a small mouth with downward slanting corners. Visceral anomalies included congenital heart disease (patent ductus arteriosus), hydronephrosis, and decrease in intestinal motility. The only other postaxial deficiency syndrome with bilateral deficiency of the fifth digital rays of all 4 limbs associated with orofacial and visceral anomalies is the postaxial acrofacial dysostosis syndrome delineated by Miller. Our patient appears to present a new form of postaxial acrofacial dysostosis. The hand and foot anomalies of our patient are more severe and the orofacial and ear anomalies are completely different. On the other hand, our patient lacks some key manifestations of other postaxial acrofacial dysostoses, such as cleft palate, cup-shaped ears, coloboma and ectropion of the eyelids, and ulnar hypoplasia or radial ulnar synostosis. Close parental consanguinity associated with this disorder suggests an autosomal recessive inheritance. As more cases of this disorder are reported, clarity regarding the matter of inheritance and heterogeneity will become apparent-a point crucial in genetic counseling.
REFERENCES Barbuti D, Drazi C, Reale A, Paradisi C (1989): Postaxial acrofacial dysostosis or Miller syndrome-A case report. Eur J Pediatr 148:445-446.
443
BirchJensen A (1949): Congenital deformities of the upper extremities. Domus Biol Hered Humanae Univ Hafiensis. Odense and Copenhagen: Ejnar Munskgaards, Beobachtung 19206. Chrzanowska KH, Fryns JP, Krajewska-Walesek M, Wisniewski L, Van den Benghe H (1989): Phenotype variability in the Miller acrofacial dysostosis syndrome. Report of two further patients. Clin Genet 35157-160. Donnai D, Hughes HE, Winter RM (1987):Postaxial acrofacial dysostosis (Miller) syndrome. J Med Genet 24:422-425. Fineman RM (1981):Recurrence of the postaxial acrofacial dysostosis syndrome in a sibship: Implications for genetic counseling. J Pediatr 98:87-88. Fryns JP, Van den Berghe H (1988):Acrofacial dysostosis with postaxial limb deficiency. Am J Med Genet 29:205-208. Gen6e E (1969):Une forme extensive de dysostose mandibulofaciale.J GBn6t Hum 17:45-52. Hauss-Albert H (1988):Postaxial acrofacial dysostosis syndrome with microcephaly, seizures, and profound mental retardation. Am J Med Genet 31:701-703. Meinecke P, Wiedemann HR (1987): Letter t o the Editor: Robin sequence and oligodactyly in mother and son-Probably a further example of the postaxial acrofacial dysostosis syndrome. Am J Med Genet 27:953-956. Miller M, Fineman R, Smith DW (1979):Postaxial acrofacial dysostosis syndrome. J Pediatr 95970-975. Opitz JM, Stickler GB (1987): Letter to the Editor: The GenBe-Wiedemann syndrome, a n acrofacial dysostosi+Further observation. Am J Med Genet 27:971-975. Richards M (1987):Miller syndrome: Anaesthetic management of postaxial acrofacial dysostosis. Anaesthesia 42:871-874. Richierie-Costa A, Guion-Almeida ML (1989):Postaxial acrofacial dysostosis: Report of a Brazilian patient. Am J Med Genet 33:447-449. Rodriguez JI, Palacios J , Urioste M (1990):New acrofacial dysostosis syndrome in 3 sibs. Am J Med Genet 35:484-489. Rosselli D, Gulienetti R (1960): “Le Malformazioni Associate.” Turin: Edizione Minerva Medica, pp 157-158. Smith DW, Pashayan H, Wildervanck LS (1975):Case Report 28. Syndrome Identification 3:7-13. Wiedemann HR (1973): Mipbildungs-Retardierungs-Syndrommit Fehlen des 5. Strahls a n Handen und Fiipen, Gaumenspalte, dysplastischen Ohren und Augenlidern und radioulnarer Synostose. Klin Padiatr 185181-186.
