American Journal of Medical Genetics 35:490-492 (1990)
Severe Postaxial Acrofacial Dysostosis: An Anatomic and Angiographic Study Jose Ignacio Rodriguez and Jose Palacios Department of Pathology, L a Paz Hospital, Madrid, Spain
We describe a severe case of postaxial acrofacia1 dysostosis syndrome [POADS] or GeneeWiedemann syndrome in a stillborn female. The report includes an arteriographicand anatomic study of the limbs. Previously unreported findings such as hypoplasiaof the femora, ossification defect of the ischium and pubis, bilobed tongue, and lung hypoplasia were noted. This case documents further variability in the POADS or Genee-Wiedemann syndrome.
ing a 36-week gestation. There was no known consanguinity and no birth defects on either side of the family. There was no history of possible teratogenic exposure. The infant (Fig. 1A) was moderately macerated, and the umbilical cord contained 2 vessels and was of normal length. The placenta was normal. Birthweight was 580 g (< 5th centile), overall length was 28cm (< 5th centile), crown-rump length was 23 cm, and head circumference was 24 cm. Craniofacial anomalies included maxillary, mandibular, and malar hypoplasia, low-set and malformed ears, broad nasal bridge, and wide U-shaped coloboma of the lower left eyelid (Fig. 1B).The soft palate had a posterior KEY WORDS: Genee-Wiedemannsyndrome, midline cleft, and the tongue was bilobed. Upper limbs acrofacial dysostosis, ulnar were symmetrically short with bilateral syndactyly of hypoplasia, femoral hypothe 4th and 5th fingers (Figs. lC, D). Radiographs plasia, fibular hypoplasia, showed hypoplastic scapulae with absence of the lower limb arteriography half bilaterally, short and broad clavicles, absence of ulnae, incurving of the radii, bilateral synostosis of the 4th and 5th metacarpals, and hypoplastic left first digital ray (Fig. 2). Lower limbs were symmetrical, short, INTRODUCTION The postaxial acrofacial dysostosis syndrome and bowed. The 3rd left toe was hypoplastic, and there (POADS) [Miller et al., 19791or Genee-Wiedemann syn- was syndactyly of the left 4th and 5th toes. Radiographs drome [Opitz and Stickler, 19871 consists of a mandi- showed only one long bone with the same findings in bulofacial dysostosis and postaxial limb deficiency. The both limbs. Metatarsals and first phalanges had a norpatients have predominantly absence or incomplete de- mal appearance but the remaining phalanges were abvelopment of the 5th digital rays and to a lesser degree sent or poorly ossified (Figs. 2, 3C). Radiographs of the spine showed 11ribs bilaterally, 8 some preaxial defects [Genee, 1969; Miller et al, 1979; cervical vertebrae, hemivertebrae in the sacrum, and Meinecke and Wiedemann, 19871. Most reported paabsence of ischial and pubic bones with only one ossificatients are alive, and their development is normal. Howtion point in the acetabular region. ever, great clinical variability has been described [Opitz Anatomic studies in both forearms showed a short and Stickler, 1987; Meinecke and Wiedemann, 19871. We report on a case of lethal fetal POADS with more nonossified ulna and a complete cartilaginous synostosevere manifestations than were found in most of the sis without joint space formation between the humerus previously described cases. We add the findings of a n and radius (Fig. 3B). Angiography of the upper limb showed a normal humeral artery that bifurcated a t the angiographic and anatomic study of the limbs. elbow into main branches; the external one followed the radius to reach the hand, and the internal branch folCLINICAL REPORT The infant was a stillborn girl delivered to a 27-year- lowed the internal side of the forearm and had a greater old primigravid mother and a 30-year-old father follow- diameter than the external one. A third branch originating from the ulnar artery appeared between them (Fig. 3A). In the lower limbs, there was a very hypoplastic carReceived for publication June 8,1989; revision received May 29, tilaginous femur completely fused to a bowed tibia. Fib1989. Address reprint requests to Dr. Jose Ignacio Rodriguez, Departa- ula was represented by 2 separated fragments of carmento de Anatomia Patologica, Hospital La Paz, Paseo de la Cast- tilage attached to the proximal anddistal external edges of the tibia. Ischial and pubic segments existed in a ellana 261, 28046 Madrid, Spain.
0 1990 Wiley-Liss, Inc.
Postaxial Acrofacial Dysostosis
491
Fig. 1.A General appearance of the patient. Note the short limbs. B: Facial appearance: micrognathia, broad nasal bridge, and coloboma of the left eyelid. C, D Hands of the patient. Note syndactyly and proximally inserted thumbs.
Fig. 3. A Upper limb arteriography. B. Dissection of the upper limb. Note the presence of a short ulna and a humero-radial synostosis. C: Lower limb arteriography. The only ossified long bone is the tibia; midshaft dark lines correspond with the vascular supply passing through the thickened cortical bone in the bowed zone. D: Dissection of the same lower limb. Note hypoplastic femur (large arrowhead) attached to the proximal tibial epiphysis. Also note the bowed tibia and a fibula in 2 fragments (small arrowheads).
cartilaginous state (Fig. 3D). The arteriographic study showed a short femoro-popliteal artery that branched into many small arteries near the acetabulum to reach the hypoplastic femur. The bifurcation in the anterior and the posterior tibial arteries occurred normally. The latter gave origin to the fibular artery (Fig. 3 0 . Lung hypoplasia (lung-to-body weight ratio 0,013:l) [Wigglesworth, 19841 was the only visceral anomaly found.
Fig. 2. Radiograph of the patient
DISCUSSION The craniofacial and limb findings in this patient are consistent with the POADS or Gen6e-Wiedemann syndrome, in which the fetal presentation and its lethal character are unusual. Moreover, this case presents other anomalies such as hypoplastic scapulae, supranumerary cervical vertebra, sacral column segmentation defect, and a single umbilical artery that have been occasionally reported [Poissonnier et al., 1983; Opitz
492
Rodriguez and Palacios
and Stickler, 19871. Our case adds some abnormalities such a s the radiological absence of the femur, ischium, and pubis, the bilobed tongue, and the lung hypoplasia not previously described to our knowledge. The presence of a normal arterial pattern in both forearms could be in favor of the existence of ulna and radius, as our anatomic study demonstrated. The ulna existed as a short cartilaginous piece not detected by radiographs. The same situation occurred in the study of the lower limbs: 2 pelvic bones and a single long bone were only seen in the X-rays, but a very hypoplastic femur and a n incomplete fibula separated into 2 segments was demonstrated anatomically. Thus, a severe delay of ossification exists in this syndrome, and it seems better to describe them, in the radiological studies, as absence of ossification instead of absence of one or more bones. Arteriography is recommended in some cases. The case reported by Poissonnier et al. [19831and our own case document further variability and severity in the POADS or Genee-Wiedemann syndrome in which a n autosomal recessive inheritance is accepted. Other reports of acrofacial dysostosis and severe limb reduction [Kawira et al., 1984; Goldstein and Mirkin, 19881have been included as a severe form of Nager syndrome or as a new type of acrofacial dysostosis. If they are not a new syndrome, these cases could be a severe form of POADS because they present pre- and postaxial limb deficien-
cies and severe lower limbs reduction, manifestations not described in the Nager syndrome.
ACKNOWLEDGMENTS The authors are grateful t o Dr. E. Delgado for his technical assistance in the anatomic study. This work has been partially supported by Caja Madrid.
REFERENCES Genee E (1969): Une forme extensive de dysostose mandibulofaciale.J Genet Hum 17:45-52. Goldstein DJ, Mirkin LD (1988):Nager acrofacial dysostosis: Evidence for apparent heterogeneity. Am J Med Genet 30:741-746. Kawira EL, Weaver DD, Bender HA (1984): Acrofacial dysostosis with severe facial clefting and limb reduction. Am J Med Genet 17:641-647. Meinecke P, Wiedemann HR (1987):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 95:970-975. Opitz JM, Stickler GB (1987): The Genee-Wiedemann syndrome, a n acrofacial d y s o s t o s i s h r t h e r observation. Am J Med Genet 27:971-975. Poissonnier M, Neuville V, Petit Ph, Busutil R (1983):Dysostose mandibulofaciale et ulnofibulare lethale. Ann Pediatr (Paris) 30:713-717. Wigglesworth JS (1984): “Perinatal Pathology. Major Problems in Pathology.” Philadelphia: Saunders, p 175.
Severe Postaxial Acrofacial Dysostosis: An Anatomic and Angiographic Study Jose Ignacio Rodriguez and Jose Palacios Department of Pathology, L a Paz Hospital, Madrid, Spain
We describe a severe case of postaxial acrofacia1 dysostosis syndrome [POADS] or GeneeWiedemann syndrome in a stillborn female. The report includes an arteriographicand anatomic study of the limbs. Previously unreported findings such as hypoplasiaof the femora, ossification defect of the ischium and pubis, bilobed tongue, and lung hypoplasia were noted. This case documents further variability in the POADS or Genee-Wiedemann syndrome.
ing a 36-week gestation. There was no known consanguinity and no birth defects on either side of the family. There was no history of possible teratogenic exposure. The infant (Fig. 1A) was moderately macerated, and the umbilical cord contained 2 vessels and was of normal length. The placenta was normal. Birthweight was 580 g (< 5th centile), overall length was 28cm (< 5th centile), crown-rump length was 23 cm, and head circumference was 24 cm. Craniofacial anomalies included maxillary, mandibular, and malar hypoplasia, low-set and malformed ears, broad nasal bridge, and wide U-shaped coloboma of the lower left eyelid (Fig. 1B).The soft palate had a posterior KEY WORDS: Genee-Wiedemannsyndrome, midline cleft, and the tongue was bilobed. Upper limbs acrofacial dysostosis, ulnar were symmetrically short with bilateral syndactyly of hypoplasia, femoral hypothe 4th and 5th fingers (Figs. lC, D). Radiographs plasia, fibular hypoplasia, showed hypoplastic scapulae with absence of the lower limb arteriography half bilaterally, short and broad clavicles, absence of ulnae, incurving of the radii, bilateral synostosis of the 4th and 5th metacarpals, and hypoplastic left first digital ray (Fig. 2). Lower limbs were symmetrical, short, INTRODUCTION The postaxial acrofacial dysostosis syndrome and bowed. The 3rd left toe was hypoplastic, and there (POADS) [Miller et al., 19791or Genee-Wiedemann syn- was syndactyly of the left 4th and 5th toes. Radiographs drome [Opitz and Stickler, 19871 consists of a mandi- showed only one long bone with the same findings in bulofacial dysostosis and postaxial limb deficiency. The both limbs. Metatarsals and first phalanges had a norpatients have predominantly absence or incomplete de- mal appearance but the remaining phalanges were abvelopment of the 5th digital rays and to a lesser degree sent or poorly ossified (Figs. 2, 3C). Radiographs of the spine showed 11ribs bilaterally, 8 some preaxial defects [Genee, 1969; Miller et al, 1979; cervical vertebrae, hemivertebrae in the sacrum, and Meinecke and Wiedemann, 19871. Most reported paabsence of ischial and pubic bones with only one ossificatients are alive, and their development is normal. Howtion point in the acetabular region. ever, great clinical variability has been described [Opitz Anatomic studies in both forearms showed a short and Stickler, 1987; Meinecke and Wiedemann, 19871. We report on a case of lethal fetal POADS with more nonossified ulna and a complete cartilaginous synostosevere manifestations than were found in most of the sis without joint space formation between the humerus previously described cases. We add the findings of a n and radius (Fig. 3B). Angiography of the upper limb showed a normal humeral artery that bifurcated a t the angiographic and anatomic study of the limbs. elbow into main branches; the external one followed the radius to reach the hand, and the internal branch folCLINICAL REPORT The infant was a stillborn girl delivered to a 27-year- lowed the internal side of the forearm and had a greater old primigravid mother and a 30-year-old father follow- diameter than the external one. A third branch originating from the ulnar artery appeared between them (Fig. 3A). In the lower limbs, there was a very hypoplastic carReceived for publication June 8,1989; revision received May 29, tilaginous femur completely fused to a bowed tibia. Fib1989. Address reprint requests to Dr. Jose Ignacio Rodriguez, Departa- ula was represented by 2 separated fragments of carmento de Anatomia Patologica, Hospital La Paz, Paseo de la Cast- tilage attached to the proximal anddistal external edges of the tibia. Ischial and pubic segments existed in a ellana 261, 28046 Madrid, Spain.
0 1990 Wiley-Liss, Inc.
Postaxial Acrofacial Dysostosis
491
Fig. 1.A General appearance of the patient. Note the short limbs. B: Facial appearance: micrognathia, broad nasal bridge, and coloboma of the left eyelid. C, D Hands of the patient. Note syndactyly and proximally inserted thumbs.
Fig. 3. A Upper limb arteriography. B. Dissection of the upper limb. Note the presence of a short ulna and a humero-radial synostosis. C: Lower limb arteriography. The only ossified long bone is the tibia; midshaft dark lines correspond with the vascular supply passing through the thickened cortical bone in the bowed zone. D: Dissection of the same lower limb. Note hypoplastic femur (large arrowhead) attached to the proximal tibial epiphysis. Also note the bowed tibia and a fibula in 2 fragments (small arrowheads).
cartilaginous state (Fig. 3D). The arteriographic study showed a short femoro-popliteal artery that branched into many small arteries near the acetabulum to reach the hypoplastic femur. The bifurcation in the anterior and the posterior tibial arteries occurred normally. The latter gave origin to the fibular artery (Fig. 3 0 . Lung hypoplasia (lung-to-body weight ratio 0,013:l) [Wigglesworth, 19841 was the only visceral anomaly found.
Fig. 2. Radiograph of the patient
DISCUSSION The craniofacial and limb findings in this patient are consistent with the POADS or Gen6e-Wiedemann syndrome, in which the fetal presentation and its lethal character are unusual. Moreover, this case presents other anomalies such as hypoplastic scapulae, supranumerary cervical vertebra, sacral column segmentation defect, and a single umbilical artery that have been occasionally reported [Poissonnier et al., 1983; Opitz
492
Rodriguez and Palacios
and Stickler, 19871. Our case adds some abnormalities such a s the radiological absence of the femur, ischium, and pubis, the bilobed tongue, and the lung hypoplasia not previously described to our knowledge. The presence of a normal arterial pattern in both forearms could be in favor of the existence of ulna and radius, as our anatomic study demonstrated. The ulna existed as a short cartilaginous piece not detected by radiographs. The same situation occurred in the study of the lower limbs: 2 pelvic bones and a single long bone were only seen in the X-rays, but a very hypoplastic femur and a n incomplete fibula separated into 2 segments was demonstrated anatomically. Thus, a severe delay of ossification exists in this syndrome, and it seems better to describe them, in the radiological studies, as absence of ossification instead of absence of one or more bones. Arteriography is recommended in some cases. The case reported by Poissonnier et al. [19831and our own case document further variability and severity in the POADS or Genee-Wiedemann syndrome in which a n autosomal recessive inheritance is accepted. Other reports of acrofacial dysostosis and severe limb reduction [Kawira et al., 1984; Goldstein and Mirkin, 19881have been included as a severe form of Nager syndrome or as a new type of acrofacial dysostosis. If they are not a new syndrome, these cases could be a severe form of POADS because they present pre- and postaxial limb deficien-
cies and severe lower limbs reduction, manifestations not described in the Nager syndrome.
ACKNOWLEDGMENTS The authors are grateful t o Dr. E. Delgado for his technical assistance in the anatomic study. This work has been partially supported by Caja Madrid.
REFERENCES Genee E (1969): Une forme extensive de dysostose mandibulofaciale.J Genet Hum 17:45-52. Goldstein DJ, Mirkin LD (1988):Nager acrofacial dysostosis: Evidence for apparent heterogeneity. Am J Med Genet 30:741-746. Kawira EL, Weaver DD, Bender HA (1984): Acrofacial dysostosis with severe facial clefting and limb reduction. Am J Med Genet 17:641-647. Meinecke P, Wiedemann HR (1987):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 95:970-975. Opitz JM, Stickler GB (1987): The Genee-Wiedemann syndrome, a n acrofacial d y s o s t o s i s h r t h e r observation. Am J Med Genet 27:971-975. Poissonnier M, Neuville V, Petit Ph, Busutil R (1983):Dysostose mandibulofaciale et ulnofibulare lethale. Ann Pediatr (Paris) 30:713-717. Wigglesworth JS (1984): “Perinatal Pathology. Major Problems in Pathology.” Philadelphia: Saunders, p 175.
