Neural Arch Stenosis and Spinal Cord Injury in Thanatophoric Dysplasia Ona Marie Faye-Petersen, MD, A. S.
Knisely, MD
\s=b\ Bony abnormalities caused by thanatophoric dysplasia affect the base of the
skull and the vertebrae as well as the ribs and appendicular long bones. We present our findings in a full-term infant with thanatophoric dysplasia in whom the posterior fossa, the rostral vertebral column, and the neuraxis at and adjoining the craniovertebral junction were studied by dissection, roentgenography, and histologic examination. In this infant, malformations of the vertebral laminae, most prominent in the basiocciput and atlas vertebra, led to compression of the rostral cervical spinal cord, causing gliosis and focal necrosis. Stenosis of the foramen magnum and spinal canal may contribute to the ventilatory insufficiency that often causes death in patients with thanatophoric dysplasia. We suggest that the causes of death in patients with thanatophoric dysplasia and other severe forms of osteochondrodysplasia should be sought in neuraxial injury rather than attributed solely to pulmonary
hypoplasia. (AJDC. 1991;145:87-89)
thanatophoric dysplasia (TD), the limbs are short, the thorax is small, and the clivus and posterior fossa are hypoplastic.1"3 These deformities result from disordered endochondral ossifica¬ tion.4 Reduced thoracic dimensions in TD are frequently associated with mod¬ erate pulmonary hypoplasia,5 to which, at least in part, death is generally as¬
cribed.1 The vertebral laminae, compo¬ nents of the neural arch, are endochonAccepted for publication June 18,1990. From the Department of Pathology, Primary Children's Medical Center (Dr Faye-Petersen) and the Departments of Hematology and Pathology, University of Utah Medical Center (Dr Knisely), Salt Lake City. Reprint requests to Department of Pathology, Children's Hospital of Pittsburgh, One Children's Pl, Pittsburgh, PA 15213-3417 (Dr Knisely).
drally formed, and stenosis of the foramen magnum has long been recog¬
nized in TD.2,3 We examined the basiocciput, vertebrae, and spinal cord of a full-term infant with TD. We found mal¬ formations, deformation, and potential¬ ly significant neuraxial injury, princi¬ pally at the level of the atlas vertebra, that may have contributed to ventila¬ tory failure. PATIENT REPORT Clinical History A 19-year-old woman presented for initial evaluation in the 42nd week of gestation by dates. She described the pregnancy, her fourth, as uncomplicated. The family his¬ tory was unremarkable. Sonography identi¬ fied short-limbed osteochondrodysplasia and breech presentation. After a short period of spontaneous labor, a male infant was born by cesarean section. Thick meconium was in the amniotic fluid. Craniomegaly, short limbs, and poor ventilatory effort were noted at birth. Endotracheal intubation was per¬ formed for pulmonary toilet; ventilatory sup¬ port was continued pending evaluation. Skel¬ etal roentgenograms showed short, curved femora, squared iliac bones, platyspondylisis, and subperiosteal juxtaphyseal spur¬ ring. These findings were consistent with TD. After consultations with the parents, ventilatory support was discontinued on the third postnatal day, and the infant died with¬ in 5 minutes. Skin fibroblasts from the infant were cultured and banked (National Insti¬ tute of General Medical Sciences Human Genetic Mutant Cell Repository GM10749, Coriell Institute for Medical Research, Cam-
den, NJ).
Necropsy Techniques After standard necropsy evisceration, the posterior fossa and rostral spinal column were excised en bloc, including the in situ neuraxis distal to the obex.6 The posterior fossa and vertebrae C-l through T-l, with the encased length of spinal cord in situ, were
fixed in 10% phosphate-buffered formalde¬ hyde solution. Individual vertebrae were separated at the levels of the intervertebral disks using sharp dissection. Roentgeno¬ grams of the posterior fossa with basiocciput and of vertebrae C-l through T-l were ex¬ posed with the specimens in contact with the cassette to avoid magnification. The verte¬ brae and fossa were decalcified in 8% sulfosalicylic acid, hemisected transversely, and embedded in paraffin. Whole-mount sections were stained with hematoxylin-eosin, Masson's trichrome, periodic acid-Schiff, Luxol fast blue-cresyl violet, Bodian, and immunoperoxidase. A portion of the spinal cord at the level of the atlas vertebra was postfixed and routinely processed for transmission electron microscopy.
Necropsy Results Findings included megalencephaly (brain weight, 577 g; normal, 7362 ± 55 g) with tem¬ poral-lobe gyral abnormalities characteristic of TD,5 posterior-fossa hypoplasia, and ros¬ tral herniation of the cerebellum through the tentorial leaflets. The lungs were hypoplastic on gross examination and weighed 29 g together (normal lung weight,' 56 ±15 g). Aspirated meconium without pneumonitis was seen on microscopic examination. The cartilaginous framework of the larynx, tra¬ chea, and bronchi was unremarkable grossly; on microscopic examination, however, archi¬ tectural immaturity and chondrocyte disar¬ ray were apparent. Sections of iliac crest and costal physes showed the effects of TD.4 Ste¬ nosis of the midportion of the ductus arteriosus, without typical postnatal proliferati ve changes, and right ventricular hypertrophy also were noted. Contact roentgenograms and tissue sec¬ tions showed malformations of the vertebral laminae, which were shortened and bowed ventrally and medially, with periosteal bony spurring and disordered ossification at the physes. Malformation was most pronounced in the basiocciput, which showed stenosis and ventral displacement of the foramen magnum (Fig 1), and in the C-l vertebra. The
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/01/2015
immature astroglial cells8 (Fig 2) were identi¬ fied ventral to the central canal and in the uncrossed corticospinal tracts. Vascular con¬ gestion with endothelial reactive changes was marked. Axonal swellings and gliosis with mature reactive astrocytes also were present (Fig 3), but were more numerous at the C-2 and C-3 levels. Gliosis with reactive astrocytes and small clusters of lipid-laden macrophages (gitter cells) were seen at the level of the foramen magnum. Gliosis was not observed caudal to the C-4 level or in the medulla immediately above the level of the foramen magnum. Reactive astrocytes stained well for glial fibrillary acid protein, while the cytoplasm of enlarged immature astroglial cells stained only faintly. Neuronal loss, degenerative changes, and pyknosis were not apparent. Transmission electron micrographs showed only advanced autolytic change that precluded meaningful ultrastructural analysis.
Fig 1.—Contact roentgenogram of the posterior fossa of the patient. The contours of the foramen magnum of an infant without osteochondrodysplasia are smooth'2; here, the occipital laminae are shortened and incurved, and the lumen of the foramen magnum is irregularly narrowed by bony protuberances that represent the physes of the occipital laminae.2,3 Note the juxtaphyseal bone spurs, one of which is indicated by an arrowhead, in the occipital laminae and body. Similar spurring Is well recognized at proximal femoral physes In thanatophoric dysplasia (original magnification 2; bar equals 1 cm).4
Fig 2.—Swollen Immature astroglial cells in the central gray matter of the spinal cord at the C-1 level. The central canal, which is flattened anteroposteriorly, is at the lower right, and the tortuous anterior spinal vessels are at the upper right (Luxol fast blue-cresyl violet, original magnification 180; bar equals 80 µ ). spinal cord was deformed at all levels, fitting snugly within the triangular lumen of the spinal canal, and was rotated 45° to the right at the L-l level.
Injury, as opposed to deformation, of the spinal cord was present from the foramen magnum through the C-3 level. It was most conspicuous at the C-l level, where swollen
COMMENT This infant with TD had abnormally short and incurved vertebral and modi¬ fied vertebral (basioccipital) laminae, with consequent stenosis of the spinal canal and foramen magnum. The entire spinal canal was stenotic, but was rela¬ tively less narrowed caudally to C-l. Our dissection did not identify a cause for rotation of the lumbar spinal cord within the spinal canal. The neural arch fit closely around the distal medulla and the rostral cervical spinal cord, which showed marked com¬ pressive deformity and injury mani¬ fested as necrosis, gliosis, and unusual cytoplasmic changes in immature as¬ troglial cells. The lesions affected pre¬ dominantly the ventral cord and were essentially limited to the region imme¬ diately caudal to the craniovertebral junction; we propose that this suggests compression ofthe cord against the dens of the axis vertebra (body of the atlas vertebra) during flexion of the head and neck. The injury seen could have led to impaired diaphragmatic function and, hence, to impaired ventilation. Gliosis, vacuolation, and macrophages in the cervical spinal cord, as documented here, have been observed in at least one other newborn with TD,5 and are consis¬ tent with antenatal onset of injury. These findings may be correlated not only with ventilatory failure but also with polyhydramnios9 (possibly due to impaired swallowing) and decreased fe¬ tal motion,10 which are both commonly
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/01/2015
HT(ASCP), performed outstanding histotechnical work. Don Morse helped greatly with photography.
References
Fig 3.—Mature reactive astrocytes (arrow) and rare swollen Immature astroglial cells in un¬ crossed corticospinal tract at the C-2 level (hematoxylin-eosln, original magnification 575; bar equals 30 µ ). associated with TD. Neural arch malformation with neuraxial deformation is recognized in other forms of osteochondrodysplasia,11"14 in which it is associated with ventilatory dysfunction that can be surgically re¬ lieved.14 Release of the neuraxis by suboccipital craniectomy has allowed two individuals with TD and ventilatory dysfunction to survive for several years; one of them had evidence of brainstem compression on measure¬ ment of auditory evoked potentials. These children remained ventilator de¬ pendent.15 Our findings indicate that compressive deformity at C-l and fora¬ men magnum levels may be a significant complication of TD. If potentially lifesparing surgery is performed to combat the effects of TD, it may be necessary to unroof the neuraxis in the rostral spinal canal as well as at the craniovertebral junction. Evaluations of thoracic wall mechanics, pulmonary function, and brain-stem and phrenic evoked poten¬ tials (to assess the extent to which ab¬ normalities in thoracic and diaphrag¬ matic conformation, anatomy of the
cartilaginous airways, and neuraxial in¬ jury may contribute to ventilatory in¬ sufficiency) should perhaps precede such procedures. To our knowledge, these studies have yet to be performed in individuals with TD.
Thoracic malformations, abnormali¬ ties in lung mesenchyme, and neuraxial injury all may be present in osteochondrodysplasia. These lesions may pro¬ duce both pulmonary hypoplasia and ventilatory insufficiency of multifactorial cause.16"18 Assessment of skeletal and neuraxial abnormalities at the cranio¬ vertebral junction and in the rostral cer¬ vical spine and spinal cord, as per¬ formed in this patient, facilitates study of the contributions of thoracic, pulmo¬ nary, and neural-arch malformations to the ventilatory insufficiency seen in many forms of osteochondrodysplasia.
1. Jones KL. Smith's Recognizable Patterns of Human Malformation. 4th ed. Philadelphia, Pa: WB Saunders Co; 1988:290-291. 2. Potter EL, Craig JM. Pathology of the Fetus and the Infant. 3rd ed. Chicago, Ill: Year Book Medical Publishers Inc; 1975:552-554. 3. Marin-Padilla M, Marin-Padilla TM. Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism). In: Bergsma D, Lowry RB, Gorlin RJ, Doran TA, Paul NW, eds. Embryology and Pathogenesis and Prenatal Diagnosis: Part D of Annual Review of Birth Defects, 1976. New York, NY: Alan R Liss Inc; 1977;13:7-23. 4. Horton WA, Hood OJ, Machado MA, Ahmed S, Griffey ES. Abnormal ossification in thanatophoric dysplasia. Bone. 1988;9:53-61. 5. Knisely AS, Ambler MW. Temporal-lobe abnormalities in thanatophoric dysplasia. Pediatr Neurosci. 1988;14:169-177. 6. Knisely AS, Singer DB. A technique for necropsy evaluation of stenosis of the foramen magnum and rostral spinal canal in osteochondrodysplasia. Hum Pathol. 1988;19:1372-1375. 7. Gruenwald P, Minh HN. Evaluation of body and organ weights in perinatal pathology, I: normal standards derived from autopsies. Am J Clin Pathol. 1960;34:247-253. 8. Privat A. Postnatal gliogenesis in the mammalian brain. Int Rev Cytol. 1975;40:281-323. 9. Thompson BH, Parmley TH. Obstetric features of thanatophoric dwarfism. Am J Obstet Gymecol. 1971;109:396-401. 10. T\l=o'\thZ, Vachter J, Szeifert G, et al. Antenatally diagnosed thanatophoric dysplasia. Acta Paediatr Hung. 1982;23:423-430. 11. Pauli RM, Scott CI, Wassman ER Jr, et al. Apnea and sudden unexpected death in infants with achondroplasia. J Pediatr. 1984;104:342-348. 12. Knisely AS, Steigman CK. Stenosis of the foramen magnum and rostral spinal canal, with spinal cord deformity, in Jeune's asphyxiating thoracic dystrophy. Pediatr Pathol. 1989;9:299-305. 13. Pauli RM, Gilbert EF. Upper cervical cord compression as cause of death in osteogenesis imperfecta type II. J Pediatr. 1986;108:579-581. 14. Reid CS, Pyeritz RE, Kopits SE, et al. Cervicomedullary compression in young patients with achondroplasia: value of comprehensive neurologic and respiratory evaluation. J Pediatr. 1987; 110:522-530. 15. MacDonald IM, Hunter AGW, MacLeod PM, MacMurray SB. Growth and development in thanatophoric dysplasia. Am J Med Genet.
1989;33:508-512.
Cunningham M, Stocks J. Werdnig-Hoffdisease: the effects of intrauterine onset on lung growth. Arch Dis Child. 1978;53:921-925. 17. Wigglesworth JS, Desai R. Effects on lung growth of cervical cord section in the rabbit fetus. Early Hum Dev. 1979;3:51-65. 18. Shapiro JR, Burn VE, Chipman SD, et al. Case report: pulmonary hypoplasia and osteogenesis imperfecta type II with defective synthesis of alpha I(1) procollagen. Bone. 1989;10:165-171. 16.
mann
This study was supported in part by grant 5T32 DK07115 from the National Institutes of Health. We thank Mary W. Ambler, MD, Margaret G. Norman, MD, and Bernd W. Scheithauer, MD, for assistance in interpreting neuropathologic find¬ ings. Kelly C. Bowles, HT(ASCP), Marnine A. Peterson, HT(ASCP), and Susan L. Wall,
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/01/2015
Knisely, MD
\s=b\ Bony abnormalities caused by thanatophoric dysplasia affect the base of the
skull and the vertebrae as well as the ribs and appendicular long bones. We present our findings in a full-term infant with thanatophoric dysplasia in whom the posterior fossa, the rostral vertebral column, and the neuraxis at and adjoining the craniovertebral junction were studied by dissection, roentgenography, and histologic examination. In this infant, malformations of the vertebral laminae, most prominent in the basiocciput and atlas vertebra, led to compression of the rostral cervical spinal cord, causing gliosis and focal necrosis. Stenosis of the foramen magnum and spinal canal may contribute to the ventilatory insufficiency that often causes death in patients with thanatophoric dysplasia. We suggest that the causes of death in patients with thanatophoric dysplasia and other severe forms of osteochondrodysplasia should be sought in neuraxial injury rather than attributed solely to pulmonary
hypoplasia. (AJDC. 1991;145:87-89)
thanatophoric dysplasia (TD), the limbs are short, the thorax is small, and the clivus and posterior fossa are hypoplastic.1"3 These deformities result from disordered endochondral ossifica¬ tion.4 Reduced thoracic dimensions in TD are frequently associated with mod¬ erate pulmonary hypoplasia,5 to which, at least in part, death is generally as¬
cribed.1 The vertebral laminae, compo¬ nents of the neural arch, are endochonAccepted for publication June 18,1990. From the Department of Pathology, Primary Children's Medical Center (Dr Faye-Petersen) and the Departments of Hematology and Pathology, University of Utah Medical Center (Dr Knisely), Salt Lake City. Reprint requests to Department of Pathology, Children's Hospital of Pittsburgh, One Children's Pl, Pittsburgh, PA 15213-3417 (Dr Knisely).
drally formed, and stenosis of the foramen magnum has long been recog¬
nized in TD.2,3 We examined the basiocciput, vertebrae, and spinal cord of a full-term infant with TD. We found mal¬ formations, deformation, and potential¬ ly significant neuraxial injury, princi¬ pally at the level of the atlas vertebra, that may have contributed to ventila¬ tory failure. PATIENT REPORT Clinical History A 19-year-old woman presented for initial evaluation in the 42nd week of gestation by dates. She described the pregnancy, her fourth, as uncomplicated. The family his¬ tory was unremarkable. Sonography identi¬ fied short-limbed osteochondrodysplasia and breech presentation. After a short period of spontaneous labor, a male infant was born by cesarean section. Thick meconium was in the amniotic fluid. Craniomegaly, short limbs, and poor ventilatory effort were noted at birth. Endotracheal intubation was per¬ formed for pulmonary toilet; ventilatory sup¬ port was continued pending evaluation. Skel¬ etal roentgenograms showed short, curved femora, squared iliac bones, platyspondylisis, and subperiosteal juxtaphyseal spur¬ ring. These findings were consistent with TD. After consultations with the parents, ventilatory support was discontinued on the third postnatal day, and the infant died with¬ in 5 minutes. Skin fibroblasts from the infant were cultured and banked (National Insti¬ tute of General Medical Sciences Human Genetic Mutant Cell Repository GM10749, Coriell Institute for Medical Research, Cam-
den, NJ).
Necropsy Techniques After standard necropsy evisceration, the posterior fossa and rostral spinal column were excised en bloc, including the in situ neuraxis distal to the obex.6 The posterior fossa and vertebrae C-l through T-l, with the encased length of spinal cord in situ, were
fixed in 10% phosphate-buffered formalde¬ hyde solution. Individual vertebrae were separated at the levels of the intervertebral disks using sharp dissection. Roentgeno¬ grams of the posterior fossa with basiocciput and of vertebrae C-l through T-l were ex¬ posed with the specimens in contact with the cassette to avoid magnification. The verte¬ brae and fossa were decalcified in 8% sulfosalicylic acid, hemisected transversely, and embedded in paraffin. Whole-mount sections were stained with hematoxylin-eosin, Masson's trichrome, periodic acid-Schiff, Luxol fast blue-cresyl violet, Bodian, and immunoperoxidase. A portion of the spinal cord at the level of the atlas vertebra was postfixed and routinely processed for transmission electron microscopy.
Necropsy Results Findings included megalencephaly (brain weight, 577 g; normal, 7362 ± 55 g) with tem¬ poral-lobe gyral abnormalities characteristic of TD,5 posterior-fossa hypoplasia, and ros¬ tral herniation of the cerebellum through the tentorial leaflets. The lungs were hypoplastic on gross examination and weighed 29 g together (normal lung weight,' 56 ±15 g). Aspirated meconium without pneumonitis was seen on microscopic examination. The cartilaginous framework of the larynx, tra¬ chea, and bronchi was unremarkable grossly; on microscopic examination, however, archi¬ tectural immaturity and chondrocyte disar¬ ray were apparent. Sections of iliac crest and costal physes showed the effects of TD.4 Ste¬ nosis of the midportion of the ductus arteriosus, without typical postnatal proliferati ve changes, and right ventricular hypertrophy also were noted. Contact roentgenograms and tissue sec¬ tions showed malformations of the vertebral laminae, which were shortened and bowed ventrally and medially, with periosteal bony spurring and disordered ossification at the physes. Malformation was most pronounced in the basiocciput, which showed stenosis and ventral displacement of the foramen magnum (Fig 1), and in the C-l vertebra. The
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/01/2015
immature astroglial cells8 (Fig 2) were identi¬ fied ventral to the central canal and in the uncrossed corticospinal tracts. Vascular con¬ gestion with endothelial reactive changes was marked. Axonal swellings and gliosis with mature reactive astrocytes also were present (Fig 3), but were more numerous at the C-2 and C-3 levels. Gliosis with reactive astrocytes and small clusters of lipid-laden macrophages (gitter cells) were seen at the level of the foramen magnum. Gliosis was not observed caudal to the C-4 level or in the medulla immediately above the level of the foramen magnum. Reactive astrocytes stained well for glial fibrillary acid protein, while the cytoplasm of enlarged immature astroglial cells stained only faintly. Neuronal loss, degenerative changes, and pyknosis were not apparent. Transmission electron micrographs showed only advanced autolytic change that precluded meaningful ultrastructural analysis.
Fig 1.—Contact roentgenogram of the posterior fossa of the patient. The contours of the foramen magnum of an infant without osteochondrodysplasia are smooth'2; here, the occipital laminae are shortened and incurved, and the lumen of the foramen magnum is irregularly narrowed by bony protuberances that represent the physes of the occipital laminae.2,3 Note the juxtaphyseal bone spurs, one of which is indicated by an arrowhead, in the occipital laminae and body. Similar spurring Is well recognized at proximal femoral physes In thanatophoric dysplasia (original magnification 2; bar equals 1 cm).4
Fig 2.—Swollen Immature astroglial cells in the central gray matter of the spinal cord at the C-1 level. The central canal, which is flattened anteroposteriorly, is at the lower right, and the tortuous anterior spinal vessels are at the upper right (Luxol fast blue-cresyl violet, original magnification 180; bar equals 80 µ ). spinal cord was deformed at all levels, fitting snugly within the triangular lumen of the spinal canal, and was rotated 45° to the right at the L-l level.
Injury, as opposed to deformation, of the spinal cord was present from the foramen magnum through the C-3 level. It was most conspicuous at the C-l level, where swollen
COMMENT This infant with TD had abnormally short and incurved vertebral and modi¬ fied vertebral (basioccipital) laminae, with consequent stenosis of the spinal canal and foramen magnum. The entire spinal canal was stenotic, but was rela¬ tively less narrowed caudally to C-l. Our dissection did not identify a cause for rotation of the lumbar spinal cord within the spinal canal. The neural arch fit closely around the distal medulla and the rostral cervical spinal cord, which showed marked com¬ pressive deformity and injury mani¬ fested as necrosis, gliosis, and unusual cytoplasmic changes in immature as¬ troglial cells. The lesions affected pre¬ dominantly the ventral cord and were essentially limited to the region imme¬ diately caudal to the craniovertebral junction; we propose that this suggests compression ofthe cord against the dens of the axis vertebra (body of the atlas vertebra) during flexion of the head and neck. The injury seen could have led to impaired diaphragmatic function and, hence, to impaired ventilation. Gliosis, vacuolation, and macrophages in the cervical spinal cord, as documented here, have been observed in at least one other newborn with TD,5 and are consis¬ tent with antenatal onset of injury. These findings may be correlated not only with ventilatory failure but also with polyhydramnios9 (possibly due to impaired swallowing) and decreased fe¬ tal motion,10 which are both commonly
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/01/2015
HT(ASCP), performed outstanding histotechnical work. Don Morse helped greatly with photography.
References
Fig 3.—Mature reactive astrocytes (arrow) and rare swollen Immature astroglial cells in un¬ crossed corticospinal tract at the C-2 level (hematoxylin-eosln, original magnification 575; bar equals 30 µ ). associated with TD. Neural arch malformation with neuraxial deformation is recognized in other forms of osteochondrodysplasia,11"14 in which it is associated with ventilatory dysfunction that can be surgically re¬ lieved.14 Release of the neuraxis by suboccipital craniectomy has allowed two individuals with TD and ventilatory dysfunction to survive for several years; one of them had evidence of brainstem compression on measure¬ ment of auditory evoked potentials. These children remained ventilator de¬ pendent.15 Our findings indicate that compressive deformity at C-l and fora¬ men magnum levels may be a significant complication of TD. If potentially lifesparing surgery is performed to combat the effects of TD, it may be necessary to unroof the neuraxis in the rostral spinal canal as well as at the craniovertebral junction. Evaluations of thoracic wall mechanics, pulmonary function, and brain-stem and phrenic evoked poten¬ tials (to assess the extent to which ab¬ normalities in thoracic and diaphrag¬ matic conformation, anatomy of the
cartilaginous airways, and neuraxial in¬ jury may contribute to ventilatory in¬ sufficiency) should perhaps precede such procedures. To our knowledge, these studies have yet to be performed in individuals with TD.
Thoracic malformations, abnormali¬ ties in lung mesenchyme, and neuraxial injury all may be present in osteochondrodysplasia. These lesions may pro¬ duce both pulmonary hypoplasia and ventilatory insufficiency of multifactorial cause.16"18 Assessment of skeletal and neuraxial abnormalities at the cranio¬ vertebral junction and in the rostral cer¬ vical spine and spinal cord, as per¬ formed in this patient, facilitates study of the contributions of thoracic, pulmo¬ nary, and neural-arch malformations to the ventilatory insufficiency seen in many forms of osteochondrodysplasia.
1. Jones KL. Smith's Recognizable Patterns of Human Malformation. 4th ed. Philadelphia, Pa: WB Saunders Co; 1988:290-291. 2. Potter EL, Craig JM. Pathology of the Fetus and the Infant. 3rd ed. Chicago, Ill: Year Book Medical Publishers Inc; 1975:552-554. 3. Marin-Padilla M, Marin-Padilla TM. Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism). In: Bergsma D, Lowry RB, Gorlin RJ, Doran TA, Paul NW, eds. Embryology and Pathogenesis and Prenatal Diagnosis: Part D of Annual Review of Birth Defects, 1976. New York, NY: Alan R Liss Inc; 1977;13:7-23. 4. Horton WA, Hood OJ, Machado MA, Ahmed S, Griffey ES. Abnormal ossification in thanatophoric dysplasia. Bone. 1988;9:53-61. 5. Knisely AS, Ambler MW. Temporal-lobe abnormalities in thanatophoric dysplasia. Pediatr Neurosci. 1988;14:169-177. 6. Knisely AS, Singer DB. A technique for necropsy evaluation of stenosis of the foramen magnum and rostral spinal canal in osteochondrodysplasia. Hum Pathol. 1988;19:1372-1375. 7. Gruenwald P, Minh HN. Evaluation of body and organ weights in perinatal pathology, I: normal standards derived from autopsies. Am J Clin Pathol. 1960;34:247-253. 8. Privat A. Postnatal gliogenesis in the mammalian brain. Int Rev Cytol. 1975;40:281-323. 9. Thompson BH, Parmley TH. Obstetric features of thanatophoric dwarfism. Am J Obstet Gymecol. 1971;109:396-401. 10. T\l=o'\thZ, Vachter J, Szeifert G, et al. Antenatally diagnosed thanatophoric dysplasia. Acta Paediatr Hung. 1982;23:423-430. 11. Pauli RM, Scott CI, Wassman ER Jr, et al. Apnea and sudden unexpected death in infants with achondroplasia. J Pediatr. 1984;104:342-348. 12. Knisely AS, Steigman CK. Stenosis of the foramen magnum and rostral spinal canal, with spinal cord deformity, in Jeune's asphyxiating thoracic dystrophy. Pediatr Pathol. 1989;9:299-305. 13. Pauli RM, Gilbert EF. Upper cervical cord compression as cause of death in osteogenesis imperfecta type II. J Pediatr. 1986;108:579-581. 14. Reid CS, Pyeritz RE, Kopits SE, et al. Cervicomedullary compression in young patients with achondroplasia: value of comprehensive neurologic and respiratory evaluation. J Pediatr. 1987; 110:522-530. 15. MacDonald IM, Hunter AGW, MacLeod PM, MacMurray SB. Growth and development in thanatophoric dysplasia. Am J Med Genet.
1989;33:508-512.
Cunningham M, Stocks J. Werdnig-Hoffdisease: the effects of intrauterine onset on lung growth. Arch Dis Child. 1978;53:921-925. 17. Wigglesworth JS, Desai R. Effects on lung growth of cervical cord section in the rabbit fetus. Early Hum Dev. 1979;3:51-65. 18. Shapiro JR, Burn VE, Chipman SD, et al. Case report: pulmonary hypoplasia and osteogenesis imperfecta type II with defective synthesis of alpha I(1) procollagen. Bone. 1989;10:165-171. 16.
mann
This study was supported in part by grant 5T32 DK07115 from the National Institutes of Health. We thank Mary W. Ambler, MD, Margaret G. Norman, MD, and Bernd W. Scheithauer, MD, for assistance in interpreting neuropathologic find¬ ings. Kelly C. Bowles, HT(ASCP), Marnine A. Peterson, HT(ASCP), and Susan L. Wall,
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/01/2015
