American Journal of Medical Genetics 36:440-443 (1990)
Boomerang Dysplasia I. Winship, B. Cremin, and P. Beighton MRC Unit for Inherited Disorders of the Skeleton, Department of Human Genetics, University of Cape Town Medical School (I.W., P.B.), and Department of Radiology, Red Cross Children’s Hospital and University of Cape Town, (B.C.),Cape Town, South Africa
Boomerang dysplasia is a recently delineated form of neonatally lethal dwarfism. A fourth case has been investigated and an increased range of phenotypic manifestations is documented in this article. So far all affected infants have been males and X-linked recessive inheritance is possible. Diagnostic criteria for Boomerang dysplasia are outlined.
KEY WORDS: lethal dwarfism, neonatal death dwarfism, skeletaldysplasia INTRODUCTION Boomerang dysplasia was first reported as a new form of“neonata1death dwarfism” by Kozlowski et al. [19811. An earlier report by Piepkorn et al. [19771 of a lethal neonatal dwarfing condition was almost certainly describing the same entity. Two further cases were documented by Tenconi et al. [1983] and Kozlowski et al. [19851, and with description of the third case of the disorder, separate syndromic status was suggested. We have investigated a further example of this lethal malformation, and our observations are presented in this article in order to further delineate the phenotype. This entity has hitherto only been recorded in the radiological literature. CLINICAL REPORT A black male South African infant was born to a healthy 29-year-oldmother gravida 3, para 3. There was no relevant family history and no parental consanguinity. A brother and sister were normal. There had been no early complications to the pregnancy until preterm labor began at 32 weeks; at this time polyhydramnios was noted and short limbs were detected on prenatal radiographs. Ultrasonographic examination of the fetus was not available. Labor continued and a breech
Fkceived for publication June 23,1989; revision received November 20, 1989. Address reprint requests to Dr. Ingrid Winship, Department of Human Genetics, University of Cape Town Medical School, Observatory 7925, Cape Town, South Africa.
0 1990 Wiley-Liss, Inc.
extraction of the infant was performed. Death ensued within one minute after birth. The major clinical manifestations were striking shortness and deformity of all 4 limbs. The face was flat and the fontanelles were wide with a defect in the frontoethmoid region and a frontal encephalocoele. Radiological examination demonstrated marked abnormalities of the long bones together with changes in the skull, chest, spine, and pelvis (Figs. 1,2). Postmortem examination was undertaken; macroscopic and histologic examination of internal organs did not show any significant abnormalities, Chromosome analysis was unsuccessful as the postmortem cell culture failed. Case details are compared with the previously documented instances of Boomerang dysplasia in Tables 1-111.
DISCUSSION Boomerang dysplasia is now recognized as an entity and this fourth case report represents further evidence for autonomous syndromic identity. The phenotype has been consistent in the initial reports [Kozlowski et al., 1981,1985; Tenconi et al., 19831;dwarfism with normal head circumference is usual, with gross shortness and deformity of all 4 limbs. Partial or complete syndactyly of fingers and toes is another consistent finding. Variations in size of the previously reported infants may be attributed to gestational age. Radiographically, long bones may be absent, hypoplastic, or abnormally modelled, having a characteristic flat, curved contour reminiscent of the Australian boomerang-hence the designation “boomerang dysplasia.” In the digits, ossification is restricted to terminal phalanges. Consistent pelvic anomalies include hypoplastic ilia and absent pubic bones, although ischial bodies are well developed. Skull radiographs in 2 cases were normal [Kozlowski et al., 1981;Tenconi et al., 19831;the third showed poorly ossified cranial bones and a defect in the frontal bones [Kozlowski et al., 19851 Retarded ossification of the spine was a consistent feature [Kozlowski et al., 1981, 1985; Tenconi et al., 19831; other vertebral anomalies were variable. As with the clinical phenotype, these radiographic changes may be related to gestational duration. While conforming to the basic phenotype of Boomerang dysplasia, the case which we studied displayed sev-
Boomerang Dysplasia
441
Fig. 1. Frontal radiograph of the infant (postmortem) displaying the skeletal dysplasia. The short humeri, shortened “boomerang”-shaped radii femora, and tibia are noted. The iliac bones are narrow at their base and the ischia are prominent. The ribs are thin, the chest bellshaped, and the clavicles elongated. The mid-thoracic spinal canal narrows and lumbar canal widens. Ossification of hands and feet is virtually absent.
Fig. 2. Lateral radiograph of the spine demonstrates coronal clefts. In the skull, occipital bone, calvaria, and upper facial bones show underdevelopment.
era1 additional or variant defects. The anterior defect of the skull, with a frontal encephalocele,was noteworthy. The base of the skull was thickened with stenosis of the foramen magnum and enlargement of the posterior clinoid process. The chest was bell-shaped, the ribs were short and slender, and the clavicles were remarkably elongated and curved. These findings were similar to those of the original reports. The humeri were represented by tiny spicules of bones; humeri were absent in 2 of the 3 previous cases [Kozlowski et al., 1981,19851; in the third, the humeral ossification centres were severely
aplastic [Tenconi et al., 19831. The spine was underossified and in the AP views there was remarkable constriction and dilation of the spinal canal. Ischial bodies were prominent as in the other reported cases. Small pubic bones were present, contrary to previously documented absence of pubic bones. In the 3 previously recorded infants, the most significant changes were in the long bones; while similar changes were evident in this case, gross abnormalities were present in the axial skeleton. Boomerang dysplasia appears to be a distinct entity.
TABLE I. Genetic Data
Ethnic group Maternal age Paternal a& Polyhydramnios detected Fetal movement Age at death
Kozlowski et al. [1981] Japanese
Tenconi et al. [1983] Italian
29 32 35/52 Unknown Stillbirth
35 38 35/52 4/12 -
Kozlowski et al. [1985] Australian (European) 33
Present case South African (Negro) 29
28/52 Unknown 40 minutes
24/52 Unknown 1 minute
-
-
Winship et al.
442
TABLE 11. Clinical Manifestations
Age at birth Weight (g) Length (cm) Head circumference (cm) Face
Kozlowski et al. [1981] 35/52 1,850
-
Tenconi et ai. [1983] 36/52 2,450 38 56.6
“Mongoloid
High full forehead
-
Anterior fontanelle
Large
Frontal bones
Defect at anterior part replaced by firm membrane
Nose
Mouth Mid face Mandible Trunk and neck Limbs Upper Arms Hands
Palmar creases Nails Lower Legs Feet
Kozlowski et al. [1985] 30152 400 24 29.5
-
Trunk shortened
Shortened
-
-
Shortened
-
Present case 32/52 2,280 35 38
Flat face prominent cheeks Large fontanelle sulcus splayed 3 cm defect between frontal bones
Broad nasal root, hypoplasia nasal septum, nares slanted Cleft palate Malar hypoplasia Micrognathia Short trunk, short neck
-
Severe micromelia Duplication of terminal phalanx of 2nd finger Complete syndactyly 3rd & 4th fingers Bilateral clinodactyly 5th fingers 1 crease bilaterally Hypoplastic
Short and bowed Digits partly fused
Micromelia anterior bowing femora and tibia Small feet
Very short and bowed
Short, distorted
Toes partly fused, 4 toes on each foot
-
Extreme extroversion of feet Normal Bilateral
Males, both testes undescended Omphalocoele
Males, testes in inguinal canal Frontal encephalocoele
Nails Congenital talipes equino varus Genitalia
-
-
Male
Other
-
Male, testes unpalpable
Bilateral
-
Conditions which enter into the differential diagnosis are the lethal dwarfing dysplasias, in particular atelosteogenesis and achondrogenesis. The features in the hands are very similar in ossification pattern to atelosteogenesis, where there is ossification of the distal phalanges only. However, the constellation of the features of this malformation permits the diagnosis of Boomerang dysplasia. Demonstration of histological changes in bone and cartilage may be a useful adjunct to clinical diagnosis; however, these may be similar to the changes seen in atelogenesis [Kozlowski et al., 19851. Each of the affected infants was from a different population group, viz. Japanese, Italian, Australian (European), and South African Negro. Kozlowski et al. [19851 addressed the question of the morphogenesis of this malformation and postulated that there may have been inversion of the developmental
Flat bridge of nose
Normal shape Dimple below mouth Webbed neck
Short Partial syndactyly
Rudimentary Clubbed
fields around the axis of the knee and that the thigh anlagen, with 2 ossification centres, corresponded to the unossified tibia and fibula. They also suggested that one of the ossification centres might be an ectopic fibular anlage. In the patient whom we studied, it was not possible to identify a fibular anlage although single ossification centres with cartilaginous epiphyses were evident a t the distal ends of the femora. The proposals made by Kozlowski et al. [19851 do not fully account for the abnormal morphogenesis in our patient, and an alternative explanation is an underlying collagen disorder with resultant bony abnormalities associated with other malformations, possibly on the basis of a single gene disorder. The genetic basis of Boomerang dysplasia is uncertain but it may be of significance that all 4 known cases were males. Two affected infants had normal sibs of both
Boomerang Dysplasia
443
TABLE 111. Radiological Manifestations Kozlowski et al. [1981] Skull
Nil of note
Nil of note
Kozlowski et al. [1985] Poorly ossified cranium Frontal defect
Spine
Spine dysplastic with retarded ossification
Retarded ossification; lower thoracic and lumbar vertebrae visible
Lateral masses and bodies of lower cervical vertebrae visible
13 ribs bilaterally
Clavicles long and curved peripherally; hypoplastic acetabulae
-
Ribs slender; manubrium sterni well ossified Scapulae well
-
Well developed Hypoplastic Absent Well developed
Iliac wings large Small Absent Well developed
Short Ossification centres aplastic Absent
Short Absent
Thorax Shoulder girdle
Pelvis Iliac crests Iliac bodies Pubic bones Ischal bodies Limbs Upper Humerii
Hypoplastic Absent
-
Short Absent
Radii
Triangular shape
Ulna
Triangular “Boomerang” Absent
Metacarpals Fingers Proximal phalanges Middle phalanges Distal phalanges Lower Femori Tibia Fibulae Metatarsals Toes
Tenconi et al. [1983]
Abnormal shape but well ossified
Not ossified
Absent
5 distal phalanges
Some ossification dysplastic Ossification
Short Absent Absent Absent Only distal phalanges
Small ossification centres in forearms Absent
Short Boomerang shaped Boomerang shaped Abnormal shape but well ossified 4 bones each foot, ? distal Phalanges
sexes. None of the marriages were consanguineous and On this histories were X-linked recessive inheritance warrants consideration.
ACKNOWLEDGMENTS w e are grateful to Dr. K. Kozlowski for his original diagnosis and to Elaine Lavin and Phillippa Webster for typing the manuscript. This work was supported by grants from the South African Research the Mauerberger Foundation. the Harry Crosslev Fund. and the University of Cape Town Staff Reseakh Fund.
South African Nepro Abnormal base of skull with stenosis of foramen magnum and enlarged clinoid process; defective ossification of occipital frontal bones Vertebral bodies underossified and having coronal clefts; the mid-thoracic spinal canal is narrow; the lumbar spinal canal is dilated Slender ribs Clavicles long and curved peripherally
Hypoplastic Present Well developed Short Tiny specules bilaterally Short Boomerang Absent
Absent
Absent
Peripheral ossification centres
2 small foci calcification
Short Absent Boomerang shaped Absent
Boomerang Boomerang Short, thickened Absent No ossification
REFERENCES Kozlowski K, Sillence D, Cortis-Jones R, Osburn R (1985):Boomerang dysplasia, Br Radial 58:369-371, Kozlowski K, Tsuruta T, Kameda Y, Kan A,Leslie G (1981):New forms of neonatal death dwarfism. Paediatr Radio1 10:155-160. Piepkorn M, Karp L, Hickok D, et al. (1977):Alethal neonatal dwarfing condition with short ribs, polysyndactyly, cranial synostosis, cleft palate, cardiovascular and urogenital anomalies and severe ossification defect. Teratology 16:345-350. Tenconi R, Kozlowski K, Laraiollia (1983): Boomerang dysplasia. A new form of neonatal death dwarfism. Fortschr Rontgenstr 138 (3):378-380.
Boomerang Dysplasia I. Winship, B. Cremin, and P. Beighton MRC Unit for Inherited Disorders of the Skeleton, Department of Human Genetics, University of Cape Town Medical School (I.W., P.B.), and Department of Radiology, Red Cross Children’s Hospital and University of Cape Town, (B.C.),Cape Town, South Africa
Boomerang dysplasia is a recently delineated form of neonatally lethal dwarfism. A fourth case has been investigated and an increased range of phenotypic manifestations is documented in this article. So far all affected infants have been males and X-linked recessive inheritance is possible. Diagnostic criteria for Boomerang dysplasia are outlined.
KEY WORDS: lethal dwarfism, neonatal death dwarfism, skeletaldysplasia INTRODUCTION Boomerang dysplasia was first reported as a new form of“neonata1death dwarfism” by Kozlowski et al. [19811. An earlier report by Piepkorn et al. [19771 of a lethal neonatal dwarfing condition was almost certainly describing the same entity. Two further cases were documented by Tenconi et al. [1983] and Kozlowski et al. [19851, and with description of the third case of the disorder, separate syndromic status was suggested. We have investigated a further example of this lethal malformation, and our observations are presented in this article in order to further delineate the phenotype. This entity has hitherto only been recorded in the radiological literature. CLINICAL REPORT A black male South African infant was born to a healthy 29-year-oldmother gravida 3, para 3. There was no relevant family history and no parental consanguinity. A brother and sister were normal. There had been no early complications to the pregnancy until preterm labor began at 32 weeks; at this time polyhydramnios was noted and short limbs were detected on prenatal radiographs. Ultrasonographic examination of the fetus was not available. Labor continued and a breech
Fkceived for publication June 23,1989; revision received November 20, 1989. Address reprint requests to Dr. Ingrid Winship, Department of Human Genetics, University of Cape Town Medical School, Observatory 7925, Cape Town, South Africa.
0 1990 Wiley-Liss, Inc.
extraction of the infant was performed. Death ensued within one minute after birth. The major clinical manifestations were striking shortness and deformity of all 4 limbs. The face was flat and the fontanelles were wide with a defect in the frontoethmoid region and a frontal encephalocoele. Radiological examination demonstrated marked abnormalities of the long bones together with changes in the skull, chest, spine, and pelvis (Figs. 1,2). Postmortem examination was undertaken; macroscopic and histologic examination of internal organs did not show any significant abnormalities, Chromosome analysis was unsuccessful as the postmortem cell culture failed. Case details are compared with the previously documented instances of Boomerang dysplasia in Tables 1-111.
DISCUSSION Boomerang dysplasia is now recognized as an entity and this fourth case report represents further evidence for autonomous syndromic identity. The phenotype has been consistent in the initial reports [Kozlowski et al., 1981,1985; Tenconi et al., 19831;dwarfism with normal head circumference is usual, with gross shortness and deformity of all 4 limbs. Partial or complete syndactyly of fingers and toes is another consistent finding. Variations in size of the previously reported infants may be attributed to gestational age. Radiographically, long bones may be absent, hypoplastic, or abnormally modelled, having a characteristic flat, curved contour reminiscent of the Australian boomerang-hence the designation “boomerang dysplasia.” In the digits, ossification is restricted to terminal phalanges. Consistent pelvic anomalies include hypoplastic ilia and absent pubic bones, although ischial bodies are well developed. Skull radiographs in 2 cases were normal [Kozlowski et al., 1981;Tenconi et al., 19831;the third showed poorly ossified cranial bones and a defect in the frontal bones [Kozlowski et al., 19851 Retarded ossification of the spine was a consistent feature [Kozlowski et al., 1981, 1985; Tenconi et al., 19831; other vertebral anomalies were variable. As with the clinical phenotype, these radiographic changes may be related to gestational duration. While conforming to the basic phenotype of Boomerang dysplasia, the case which we studied displayed sev-
Boomerang Dysplasia
441
Fig. 1. Frontal radiograph of the infant (postmortem) displaying the skeletal dysplasia. The short humeri, shortened “boomerang”-shaped radii femora, and tibia are noted. The iliac bones are narrow at their base and the ischia are prominent. The ribs are thin, the chest bellshaped, and the clavicles elongated. The mid-thoracic spinal canal narrows and lumbar canal widens. Ossification of hands and feet is virtually absent.
Fig. 2. Lateral radiograph of the spine demonstrates coronal clefts. In the skull, occipital bone, calvaria, and upper facial bones show underdevelopment.
era1 additional or variant defects. The anterior defect of the skull, with a frontal encephalocele,was noteworthy. The base of the skull was thickened with stenosis of the foramen magnum and enlargement of the posterior clinoid process. The chest was bell-shaped, the ribs were short and slender, and the clavicles were remarkably elongated and curved. These findings were similar to those of the original reports. The humeri were represented by tiny spicules of bones; humeri were absent in 2 of the 3 previous cases [Kozlowski et al., 1981,19851; in the third, the humeral ossification centres were severely
aplastic [Tenconi et al., 19831. The spine was underossified and in the AP views there was remarkable constriction and dilation of the spinal canal. Ischial bodies were prominent as in the other reported cases. Small pubic bones were present, contrary to previously documented absence of pubic bones. In the 3 previously recorded infants, the most significant changes were in the long bones; while similar changes were evident in this case, gross abnormalities were present in the axial skeleton. Boomerang dysplasia appears to be a distinct entity.
TABLE I. Genetic Data
Ethnic group Maternal age Paternal a& Polyhydramnios detected Fetal movement Age at death
Kozlowski et al. [1981] Japanese
Tenconi et al. [1983] Italian
29 32 35/52 Unknown Stillbirth
35 38 35/52 4/12 -
Kozlowski et al. [1985] Australian (European) 33
Present case South African (Negro) 29
28/52 Unknown 40 minutes
24/52 Unknown 1 minute
-
-
Winship et al.
442
TABLE 11. Clinical Manifestations
Age at birth Weight (g) Length (cm) Head circumference (cm) Face
Kozlowski et al. [1981] 35/52 1,850
-
Tenconi et ai. [1983] 36/52 2,450 38 56.6
“Mongoloid
High full forehead
-
Anterior fontanelle
Large
Frontal bones
Defect at anterior part replaced by firm membrane
Nose
Mouth Mid face Mandible Trunk and neck Limbs Upper Arms Hands
Palmar creases Nails Lower Legs Feet
Kozlowski et al. [1985] 30152 400 24 29.5
-
Trunk shortened
Shortened
-
-
Shortened
-
Present case 32/52 2,280 35 38
Flat face prominent cheeks Large fontanelle sulcus splayed 3 cm defect between frontal bones
Broad nasal root, hypoplasia nasal septum, nares slanted Cleft palate Malar hypoplasia Micrognathia Short trunk, short neck
-
Severe micromelia Duplication of terminal phalanx of 2nd finger Complete syndactyly 3rd & 4th fingers Bilateral clinodactyly 5th fingers 1 crease bilaterally Hypoplastic
Short and bowed Digits partly fused
Micromelia anterior bowing femora and tibia Small feet
Very short and bowed
Short, distorted
Toes partly fused, 4 toes on each foot
-
Extreme extroversion of feet Normal Bilateral
Males, both testes undescended Omphalocoele
Males, testes in inguinal canal Frontal encephalocoele
Nails Congenital talipes equino varus Genitalia
-
-
Male
Other
-
Male, testes unpalpable
Bilateral
-
Conditions which enter into the differential diagnosis are the lethal dwarfing dysplasias, in particular atelosteogenesis and achondrogenesis. The features in the hands are very similar in ossification pattern to atelosteogenesis, where there is ossification of the distal phalanges only. However, the constellation of the features of this malformation permits the diagnosis of Boomerang dysplasia. Demonstration of histological changes in bone and cartilage may be a useful adjunct to clinical diagnosis; however, these may be similar to the changes seen in atelogenesis [Kozlowski et al., 19851. Each of the affected infants was from a different population group, viz. Japanese, Italian, Australian (European), and South African Negro. Kozlowski et al. [19851 addressed the question of the morphogenesis of this malformation and postulated that there may have been inversion of the developmental
Flat bridge of nose
Normal shape Dimple below mouth Webbed neck
Short Partial syndactyly
Rudimentary Clubbed
fields around the axis of the knee and that the thigh anlagen, with 2 ossification centres, corresponded to the unossified tibia and fibula. They also suggested that one of the ossification centres might be an ectopic fibular anlage. In the patient whom we studied, it was not possible to identify a fibular anlage although single ossification centres with cartilaginous epiphyses were evident a t the distal ends of the femora. The proposals made by Kozlowski et al. [19851 do not fully account for the abnormal morphogenesis in our patient, and an alternative explanation is an underlying collagen disorder with resultant bony abnormalities associated with other malformations, possibly on the basis of a single gene disorder. The genetic basis of Boomerang dysplasia is uncertain but it may be of significance that all 4 known cases were males. Two affected infants had normal sibs of both
Boomerang Dysplasia
443
TABLE 111. Radiological Manifestations Kozlowski et al. [1981] Skull
Nil of note
Nil of note
Kozlowski et al. [1985] Poorly ossified cranium Frontal defect
Spine
Spine dysplastic with retarded ossification
Retarded ossification; lower thoracic and lumbar vertebrae visible
Lateral masses and bodies of lower cervical vertebrae visible
13 ribs bilaterally
Clavicles long and curved peripherally; hypoplastic acetabulae
-
Ribs slender; manubrium sterni well ossified Scapulae well
-
Well developed Hypoplastic Absent Well developed
Iliac wings large Small Absent Well developed
Short Ossification centres aplastic Absent
Short Absent
Thorax Shoulder girdle
Pelvis Iliac crests Iliac bodies Pubic bones Ischal bodies Limbs Upper Humerii
Hypoplastic Absent
-
Short Absent
Radii
Triangular shape
Ulna
Triangular “Boomerang” Absent
Metacarpals Fingers Proximal phalanges Middle phalanges Distal phalanges Lower Femori Tibia Fibulae Metatarsals Toes
Tenconi et al. [1983]
Abnormal shape but well ossified
Not ossified
Absent
5 distal phalanges
Some ossification dysplastic Ossification
Short Absent Absent Absent Only distal phalanges
Small ossification centres in forearms Absent
Short Boomerang shaped Boomerang shaped Abnormal shape but well ossified 4 bones each foot, ? distal Phalanges
sexes. None of the marriages were consanguineous and On this histories were X-linked recessive inheritance warrants consideration.
ACKNOWLEDGMENTS w e are grateful to Dr. K. Kozlowski for his original diagnosis and to Elaine Lavin and Phillippa Webster for typing the manuscript. This work was supported by grants from the South African Research the Mauerberger Foundation. the Harry Crosslev Fund. and the University of Cape Town Staff Reseakh Fund.
South African Nepro Abnormal base of skull with stenosis of foramen magnum and enlarged clinoid process; defective ossification of occipital frontal bones Vertebral bodies underossified and having coronal clefts; the mid-thoracic spinal canal is narrow; the lumbar spinal canal is dilated Slender ribs Clavicles long and curved peripherally
Hypoplastic Present Well developed Short Tiny specules bilaterally Short Boomerang Absent
Absent
Absent
Peripheral ossification centres
2 small foci calcification
Short Absent Boomerang shaped Absent
Boomerang Boomerang Short, thickened Absent No ossification
REFERENCES Kozlowski K, Sillence D, Cortis-Jones R, Osburn R (1985):Boomerang dysplasia, Br Radial 58:369-371, Kozlowski K, Tsuruta T, Kameda Y, Kan A,Leslie G (1981):New forms of neonatal death dwarfism. Paediatr Radio1 10:155-160. Piepkorn M, Karp L, Hickok D, et al. (1977):Alethal neonatal dwarfing condition with short ribs, polysyndactyly, cranial synostosis, cleft palate, cardiovascular and urogenital anomalies and severe ossification defect. Teratology 16:345-350. Tenconi R, Kozlowski K, Laraiollia (1983): Boomerang dysplasia. A new form of neonatal death dwarfism. Fortschr Rontgenstr 138 (3):378-380.
