Clinical Genetics 1979: 16: 399-404
FrontometaphyseaI dysplasia with congenital urinary tract malformations TOSHIO K.ANEMUR.4, TADAO OR11 AND MICHIHIRO OHTANI
Department o’f Pediatrics, School of Medicine, Gifu University and Department of Dermatdogy, Gifu Prefectural Huspital, Gifu City, Japan A 12-year-dd boy with unusual face and hearing loss was diagnosed as having frontometaphyseal dysplasia. He a h had congenital urinary tract malformations and chronic urinary tract infection. The cranial and facial bones of the patient were studied by roentgen cephalometric analysis.
Received 7 March, revised 10 July, accepted for publication 23 July 1979 K e y words: Frontometaphyseal dysplasia; roentgen cephalometric analysis; urinary tract
malformations.
In 1969, Gorlin & Cohen reported the case of a 19-year-old boy with unusual defects: in particular, he had marked supraorbital ridges, joint contractures, hearing loss, and splayed metaphyses of the long bones. This syndrome was called, together with a similar case described by Lischi in 1967, “Frontometaphyseal Dysplasia.” Several similar cases have been reported since; however, no previous report has expressly mentioned urological disorders. We would like to report another case with not only typical frontometaphyseal dysplasia, but also congenital urinary tract malformations. Case Report
Patient H . H . , a 12-year-old boy, was born to Japanese parents in July, 1964, after a normal third pregnancy. There is no family history of similar disorders, nor of consanguinity, and his mother has no history of abortion or stillbirth. He weighed 3.0 kg at 0009-9163/79/120399-06$M.50/0
birth after a normal delivery. His unusual face and the hearing loss were observed already in infancy. Although he began to walk at the age of 1 year and his behaviour has been appropriate to his age, he did not start speaking until the age of 6 years. H e has continued to do good work with a hearing aid at school and has been a cheerful boy of normal intelligence in spite of his disorders. He has had frequent cystitis and since he was 2 years old has often complained of pain in the region of the right testis. Physical Examination At physical examination, height was 139.5 cm (-1.9 S.D.) and weight, 31.0 kg (-1.3 S.D.). Although the patient was a wellnourished boy, his musculature was generally underdeveloped. There were marked supraorbital ridges, a wide nasal bridge, thickened soft tissue of the nares, and a hypoplastic and retracted mandible. Higharched palate, malocclusion, missing per@ 1979 Munksgaard, Copenhagen
400
KANEMURA, ORll AND OHTANl
Flg. 1. Mild pectus carinatum, poorly developed musculature, limited extension of the elbows, large hands and hammer toes.
manent teeth and retained deciduous teeth were also noted. Dental roentgenograms revealed congenital absence of 17 permanent teeth. The surface of the gingiva was markedly uneven and a small exostosis (about 5 mm in diameter) was present on the left upper alveolabial surface. The thorax was slightly asymmetrical, and mild pectus carinatum was evident. Winged scapulae were also noted. The genitalia were prepubertal, but the right testis was tender and swollen to the size of a walnut. This was found by urological examination to be due to purulent epididymitis. Restricted motion was noted in the extremital joints, and there was a 35" loss of extension in both elbows. Hammer toe deformities of the feet were also noted. The lower extremities were not of equal length.
Fig. 2. Lateral view of the skull. Note hyperostosis of the calvarium, perisutural sclerosis, prominent supraorbital ridge, absent frontal sinuses, hypoplastic maxilla and mandible, and antegonial notching of the mandible (arrow).
The distance from the greater trochanter to the lateral malleolus on the left side was 65 cm and on the right, 63 cm. Roentgenograms also showed the right femur, tibia and fibula to be shorter than the left ones. The hands were relatively large (Fig. 1). Bilateral conductive low tone hearing loss of about 50 db was detected by otologic examination. Laborutory Findings Increased numbers of leukocytes were found in the urine. Escherichia coli in the urine were found to be at 1 X lOY/ml. Excretory urography revealed bilateral hydronephrosis and hydroureter. Retrograde urography and cystography revealed the following disorders: (1) Stenosis of the external
FRONTOMETAPHYSEAL DYSPLASIA
40 1
Flg. 3A (top). Bowed radius and mild splaying of the distal metaphysis.
Fig. 4. Lower thoracic and upper lumbar spine. Moderately flattened vertebral bodies have irregular contours and deeply concave posterior edges. Those 3B (bottom). Markedly dongated and widened in the upper lumbar region have undulating proximal and middle phalanges. edges with convex protrusion.
Fig. 5. Accentuated iliac flare (arrow), acetabular protrusion, thickened femoral necks, widened ischial rami, constricted mid pelvis and coxa valga.
KANEMURA, O R l l AND OHTANl
402
Table 1 Clinical and roentgenographic features of frontometaphyseal dysplasia CaseNo.
# # # # # # # # #
Sex Age when diagnosed (years) Prominent supraorbital ridges Defective dentition Micrognathia and/or retrognathia Hearing loss High arched palate Visual disturbance Heart murmur Relatively short trunk and long extremities; large hands and feet Restricted radioulnar or elbow movement Joint contractures Poorly developed musculature Winged scapulae Scoliosis and/or lordosis Normal intelligence
1
2
3
4
5
6
7
8
9 1 0 1 1 1213
F
M
M
F
M
M
M
M
F
M
M
13 19 18 13 31 12 10 10 31
8
*
+ + + + + + + + + + + + + + - I + + +
M
M
'' 12
+ + + + + + + + +
+ +
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + +
+ + + + +
+ + + +
Roentgenographic features
# # # # # #
# # # #
Prominent supraorbital ridge "Nazi-helmet" configuration of cranial vault Hyperostosis of calvarium and/or perisutural sclerosis Absent or hypoplastic frontal sinuses Micrognathia (with antegonial notching and/or hypoplastic ascending ramus) Accentuated iliac flare Thinning of posterior ribs and/or irregular rib contours Moderate platyspondyly and/or irregular vertebral contours Acetabular protrusion Generalized undertubulation of metaphyses Wavy bowing of tibias and fibulas with genu valgum and/or tibia recurvatum Elongation of metacarpals and phalanges Selective thickening of middle phalanges of fingers Coxa valga
+
+ + + + +
+ +
+ + + + + + + + + + + + + + + +
+ + + + +
+ + + + +
+ + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + +
+ + + + + + + + + + +
+ + + + + + + + + + + + + + + + + + + + + + + + +
+
+ + + +
+ + + + + + + + + + + + +
Absence of marking means tnat the feature was denied or uncertain or not described in the literature. The features marked # were present in eight or more of all thirteen cases, or seven or more of the nine cases which were described especially in detail (cases No. 2, 3, 4, 5, 6, 7, 8. 10, 13). * died at the age of 23 * * died at the age of 17.
FRONTOMETAPHYSEAL DYSPLASIA
urethral meatus; (2) Urethral stricture at the membranous part; (3) Stenosis of the right ureterovesical junction; and (4) Left vesicoureteric reflux. Urinary excretion of mucopolysaccharides was 13.7 mg/g creatinine (in the normal range). In bone marrow, no pathologic or vacuolated cells were found. Serum growth hormone was within normal limits. Roentgenographic Studies
Skull X-ray film showed hyperostosis of the calvarium, perisutural sclerosis, prominent supraorbital ridge, absent frontal sinuses, hypoplastic maxilla and mandible, and antegonial notching of the mandible (Fig. 2). X-ray film of the forearm showed bowing of the radius and mild splaying of its distal metaphysis (Fig. 3A). I n the hands, the phalanges, particularly the proximal and middle phalanges, were found to be elongated and widened (Fig. 3B). The metacarpophalangeal pattern profile (Poznanski et al. 1972) of the patient was similar to that described by Holt et al. in 1972. The lower thoracic and upper lumbar vertebrae appeared to be flattened. These vertebral bodies had irregular contours and deeply concave posterior edges. Those in the upper lumbar region had irregular superior edges with convex protrusions (Fig. 4). Pelvis Xray film showed accentuated iliac flaring, a constricted mid pelvis, acetabular protrusion, increased distance between the femoral head and the acetabular fossa, thickening of the femoral necks, widened ischial rami and coxa valga (Fig. 5). Thinning of the lower posterior ribs was also found. For correct evaluation of the cranial and facial bones, roentgen cephalometric analysis was carried out. The following data were obtained: the antero-posterior length of the cranial base was very long, and that of the maxilla was very short; the nasion protruded forwards and upwards and the mandible was retracted backwards; the
403
mandibular corpus was markedly small; the upper incisor was markedly inclined forwards; and the occlusal plane was inclined forwards and dawn. Comment
Major findings in previous cases and our case are shown in Table 1. Our case is typical of this syndrome, except for the urological disorders which were briefly described by Sauvegrain et al. (1975) and Kassner et al. (1976). The case described by Sauvegrain et al. had dilated bilateral pyelo-calices and ureters. One of the three patients reported by Kassner et al. died from sepsis secondary to pyelonephritis and hydronephrosis. It would be of interest to investigate further the renal structures in these and other cases, because urological disorders may be part of the syndrome. Using roentgen cephalometric analysis (which is mainly used in orthodontics), we found several rather unusual features in our patient’s skull, particularly the markedly elongated antero-posterior cranial base and the shortened maxilla. These deformities seem to be characteristic of this syndrome. Acknowledgments
The authors are indebted to Kenji Ohhashi, D.D.S. and Shigeru Watabe, D.D.S., Department of Pedodontics, Gifu College of Dentistry, for co-operation in roentgen cephalometric analysis. This paper was read in part at the 122nd Tohkai District Meeting of the Japanese Pediatric Society, Nagoya, July 10, 1977. References
Danks, D. M., V. Mayne, R. K. Hall & M. C . McKinnon (1972). Frontometaphyseal dysplasia: A progressive disease of bone and connective tissue. Amer. J . Dis. Child. 123, 254-25 8.
Gorlin, R. J . & M. M. Cohen (1969). Fronto-
404
KANEMURA, O R l l AND OHTANI
metaphyseal dysplasia: A new syndrome. Amer. J . Dis. Child. 118, 487-494. Holt, J. F., G. R. Thompson & I. K. Arenberg (1972). Frontometaphyseal dysplasia. Radiol. Clin. N. Amer. 10, 225-243. Kassner, E. G., J. 0. Haller, V. H. Reddy, A. Mitarotundo & I. Katz (1976). Frontometaphyseal dysplasia: Evidence for autosomal dominant inheritance. Amer. J . Roentgenol. 127, 927-933. Lischi, G. (1967). Le torus supraorbitalis (Variation cranienne rare). J. Radiol. Electr. 48, 463466. Poznanski, A. K., S. M. Garn, J. M. Nagy & J. C. Gall (1972). Metacarpophalangeal pattern profiles in the evaluation of skeletal malformations. Radiology 104, 1-1 1. Sauvegrain, J., M. Lombard, L. Garel & D. Truscelli (1975). Dysplasie frontomitaphysaire. Ann. Radiol. 18, 155-162.
Walker, B. A. (1969). A craniodiaphyseal dysplasia or craniometaphyseal dysplasia, ? type. Birth Defects: Original Article Series 5 , 298-300. Weiss, L., W. A. Reynolds & R. T. Szymanowski (1976). Frontometaphyseal dysplasia: Evidence for dominant inheritance. Amer. J . Dis. Child. 130, 259-261.
Address: Toshio Kanemura, M.D. Department o f Pediatrics School o f Medicine Gifu University 40 Tsukasamachi Gifu City 500 Japan
FrontometaphyseaI dysplasia with congenital urinary tract malformations TOSHIO K.ANEMUR.4, TADAO OR11 AND MICHIHIRO OHTANI
Department o’f Pediatrics, School of Medicine, Gifu University and Department of Dermatdogy, Gifu Prefectural Huspital, Gifu City, Japan A 12-year-dd boy with unusual face and hearing loss was diagnosed as having frontometaphyseal dysplasia. He a h had congenital urinary tract malformations and chronic urinary tract infection. The cranial and facial bones of the patient were studied by roentgen cephalometric analysis.
Received 7 March, revised 10 July, accepted for publication 23 July 1979 K e y words: Frontometaphyseal dysplasia; roentgen cephalometric analysis; urinary tract
malformations.
In 1969, Gorlin & Cohen reported the case of a 19-year-old boy with unusual defects: in particular, he had marked supraorbital ridges, joint contractures, hearing loss, and splayed metaphyses of the long bones. This syndrome was called, together with a similar case described by Lischi in 1967, “Frontometaphyseal Dysplasia.” Several similar cases have been reported since; however, no previous report has expressly mentioned urological disorders. We would like to report another case with not only typical frontometaphyseal dysplasia, but also congenital urinary tract malformations. Case Report
Patient H . H . , a 12-year-old boy, was born to Japanese parents in July, 1964, after a normal third pregnancy. There is no family history of similar disorders, nor of consanguinity, and his mother has no history of abortion or stillbirth. He weighed 3.0 kg at 0009-9163/79/120399-06$M.50/0
birth after a normal delivery. His unusual face and the hearing loss were observed already in infancy. Although he began to walk at the age of 1 year and his behaviour has been appropriate to his age, he did not start speaking until the age of 6 years. H e has continued to do good work with a hearing aid at school and has been a cheerful boy of normal intelligence in spite of his disorders. He has had frequent cystitis and since he was 2 years old has often complained of pain in the region of the right testis. Physical Examination At physical examination, height was 139.5 cm (-1.9 S.D.) and weight, 31.0 kg (-1.3 S.D.). Although the patient was a wellnourished boy, his musculature was generally underdeveloped. There were marked supraorbital ridges, a wide nasal bridge, thickened soft tissue of the nares, and a hypoplastic and retracted mandible. Higharched palate, malocclusion, missing per@ 1979 Munksgaard, Copenhagen
400
KANEMURA, ORll AND OHTANl
Flg. 1. Mild pectus carinatum, poorly developed musculature, limited extension of the elbows, large hands and hammer toes.
manent teeth and retained deciduous teeth were also noted. Dental roentgenograms revealed congenital absence of 17 permanent teeth. The surface of the gingiva was markedly uneven and a small exostosis (about 5 mm in diameter) was present on the left upper alveolabial surface. The thorax was slightly asymmetrical, and mild pectus carinatum was evident. Winged scapulae were also noted. The genitalia were prepubertal, but the right testis was tender and swollen to the size of a walnut. This was found by urological examination to be due to purulent epididymitis. Restricted motion was noted in the extremital joints, and there was a 35" loss of extension in both elbows. Hammer toe deformities of the feet were also noted. The lower extremities were not of equal length.
Fig. 2. Lateral view of the skull. Note hyperostosis of the calvarium, perisutural sclerosis, prominent supraorbital ridge, absent frontal sinuses, hypoplastic maxilla and mandible, and antegonial notching of the mandible (arrow).
The distance from the greater trochanter to the lateral malleolus on the left side was 65 cm and on the right, 63 cm. Roentgenograms also showed the right femur, tibia and fibula to be shorter than the left ones. The hands were relatively large (Fig. 1). Bilateral conductive low tone hearing loss of about 50 db was detected by otologic examination. Laborutory Findings Increased numbers of leukocytes were found in the urine. Escherichia coli in the urine were found to be at 1 X lOY/ml. Excretory urography revealed bilateral hydronephrosis and hydroureter. Retrograde urography and cystography revealed the following disorders: (1) Stenosis of the external
FRONTOMETAPHYSEAL DYSPLASIA
40 1
Flg. 3A (top). Bowed radius and mild splaying of the distal metaphysis.
Fig. 4. Lower thoracic and upper lumbar spine. Moderately flattened vertebral bodies have irregular contours and deeply concave posterior edges. Those 3B (bottom). Markedly dongated and widened in the upper lumbar region have undulating proximal and middle phalanges. edges with convex protrusion.
Fig. 5. Accentuated iliac flare (arrow), acetabular protrusion, thickened femoral necks, widened ischial rami, constricted mid pelvis and coxa valga.
KANEMURA, O R l l AND OHTANl
402
Table 1 Clinical and roentgenographic features of frontometaphyseal dysplasia CaseNo.
# # # # # # # # #
Sex Age when diagnosed (years) Prominent supraorbital ridges Defective dentition Micrognathia and/or retrognathia Hearing loss High arched palate Visual disturbance Heart murmur Relatively short trunk and long extremities; large hands and feet Restricted radioulnar or elbow movement Joint contractures Poorly developed musculature Winged scapulae Scoliosis and/or lordosis Normal intelligence
1
2
3
4
5
6
7
8
9 1 0 1 1 1213
F
M
M
F
M
M
M
M
F
M
M
13 19 18 13 31 12 10 10 31
8
*
+ + + + + + + + + + + + + + - I + + +
M
M
'' 12
+ + + + + + + + +
+ +
+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
+ + + +
+ + + + +
+ + + +
Roentgenographic features
# # # # # #
# # # #
Prominent supraorbital ridge "Nazi-helmet" configuration of cranial vault Hyperostosis of calvarium and/or perisutural sclerosis Absent or hypoplastic frontal sinuses Micrognathia (with antegonial notching and/or hypoplastic ascending ramus) Accentuated iliac flare Thinning of posterior ribs and/or irregular rib contours Moderate platyspondyly and/or irregular vertebral contours Acetabular protrusion Generalized undertubulation of metaphyses Wavy bowing of tibias and fibulas with genu valgum and/or tibia recurvatum Elongation of metacarpals and phalanges Selective thickening of middle phalanges of fingers Coxa valga
+
+ + + + +
+ +
+ + + + + + + + + + + + + + + +
+ + + + +
+ + + + +
+ + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + + + +
+ + + + + + + + + + +
+ + + + + + + + + + + + + + + + + + + + + + + + +
+
+ + + +
+ + + + + + + + + + + + +
Absence of marking means tnat the feature was denied or uncertain or not described in the literature. The features marked # were present in eight or more of all thirteen cases, or seven or more of the nine cases which were described especially in detail (cases No. 2, 3, 4, 5, 6, 7, 8. 10, 13). * died at the age of 23 * * died at the age of 17.
FRONTOMETAPHYSEAL DYSPLASIA
urethral meatus; (2) Urethral stricture at the membranous part; (3) Stenosis of the right ureterovesical junction; and (4) Left vesicoureteric reflux. Urinary excretion of mucopolysaccharides was 13.7 mg/g creatinine (in the normal range). In bone marrow, no pathologic or vacuolated cells were found. Serum growth hormone was within normal limits. Roentgenographic Studies
Skull X-ray film showed hyperostosis of the calvarium, perisutural sclerosis, prominent supraorbital ridge, absent frontal sinuses, hypoplastic maxilla and mandible, and antegonial notching of the mandible (Fig. 2). X-ray film of the forearm showed bowing of the radius and mild splaying of its distal metaphysis (Fig. 3A). I n the hands, the phalanges, particularly the proximal and middle phalanges, were found to be elongated and widened (Fig. 3B). The metacarpophalangeal pattern profile (Poznanski et al. 1972) of the patient was similar to that described by Holt et al. in 1972. The lower thoracic and upper lumbar vertebrae appeared to be flattened. These vertebral bodies had irregular contours and deeply concave posterior edges. Those in the upper lumbar region had irregular superior edges with convex protrusions (Fig. 4). Pelvis Xray film showed accentuated iliac flaring, a constricted mid pelvis, acetabular protrusion, increased distance between the femoral head and the acetabular fossa, thickening of the femoral necks, widened ischial rami and coxa valga (Fig. 5). Thinning of the lower posterior ribs was also found. For correct evaluation of the cranial and facial bones, roentgen cephalometric analysis was carried out. The following data were obtained: the antero-posterior length of the cranial base was very long, and that of the maxilla was very short; the nasion protruded forwards and upwards and the mandible was retracted backwards; the
403
mandibular corpus was markedly small; the upper incisor was markedly inclined forwards; and the occlusal plane was inclined forwards and dawn. Comment
Major findings in previous cases and our case are shown in Table 1. Our case is typical of this syndrome, except for the urological disorders which were briefly described by Sauvegrain et al. (1975) and Kassner et al. (1976). The case described by Sauvegrain et al. had dilated bilateral pyelo-calices and ureters. One of the three patients reported by Kassner et al. died from sepsis secondary to pyelonephritis and hydronephrosis. It would be of interest to investigate further the renal structures in these and other cases, because urological disorders may be part of the syndrome. Using roentgen cephalometric analysis (which is mainly used in orthodontics), we found several rather unusual features in our patient’s skull, particularly the markedly elongated antero-posterior cranial base and the shortened maxilla. These deformities seem to be characteristic of this syndrome. Acknowledgments
The authors are indebted to Kenji Ohhashi, D.D.S. and Shigeru Watabe, D.D.S., Department of Pedodontics, Gifu College of Dentistry, for co-operation in roentgen cephalometric analysis. This paper was read in part at the 122nd Tohkai District Meeting of the Japanese Pediatric Society, Nagoya, July 10, 1977. References
Danks, D. M., V. Mayne, R. K. Hall & M. C . McKinnon (1972). Frontometaphyseal dysplasia: A progressive disease of bone and connective tissue. Amer. J . Dis. Child. 123, 254-25 8.
Gorlin, R. J . & M. M. Cohen (1969). Fronto-
404
KANEMURA, O R l l AND OHTANI
metaphyseal dysplasia: A new syndrome. Amer. J . Dis. Child. 118, 487-494. Holt, J. F., G. R. Thompson & I. K. Arenberg (1972). Frontometaphyseal dysplasia. Radiol. Clin. N. Amer. 10, 225-243. Kassner, E. G., J. 0. Haller, V. H. Reddy, A. Mitarotundo & I. Katz (1976). Frontometaphyseal dysplasia: Evidence for autosomal dominant inheritance. Amer. J . Roentgenol. 127, 927-933. Lischi, G. (1967). Le torus supraorbitalis (Variation cranienne rare). J. Radiol. Electr. 48, 463466. Poznanski, A. K., S. M. Garn, J. M. Nagy & J. C. Gall (1972). Metacarpophalangeal pattern profiles in the evaluation of skeletal malformations. Radiology 104, 1-1 1. Sauvegrain, J., M. Lombard, L. Garel & D. Truscelli (1975). Dysplasie frontomitaphysaire. Ann. Radiol. 18, 155-162.
Walker, B. A. (1969). A craniodiaphyseal dysplasia or craniometaphyseal dysplasia, ? type. Birth Defects: Original Article Series 5 , 298-300. Weiss, L., W. A. Reynolds & R. T. Szymanowski (1976). Frontometaphyseal dysplasia: Evidence for dominant inheritance. Amer. J . Dis. Child. 130, 259-261.
Address: Toshio Kanemura, M.D. Department o f Pediatrics School o f Medicine Gifu University 40 Tsukasamachi Gifu City 500 Japan
