2002-02-21-10 Neonatal Osseous Dysplasia © Guerrero www.thefetus.net/
Neonatal Osseous Dysplasia
A Sosa Olavarr?a, MD, PhD Luis D?az Guerrero, MD, Reigosa Yanis A
Perinatology Unit, Maternidad Privada Las Acacias, Valencia, Venezuela
Synonyms: Neonatal osseous dysplasia type I, atelosteogenesis type II, “Ring around the chondrocyte” dysplasia, De la Chapelle syndrome
Definition: Lethal neonatal micromelic osteochondrodysplasia with diagnostic X-ray and characteristic clinical and histopathological features.
Etiology: Autosomal recessive inheritance (1)
Genetic: Mutation in the diastrophic dysplasia sulfate transporter gene (DTDST) (2)
The patient is scanned at 17 weeks and the examination demonstrates this clubbed foot: connected to a very mesomelic limb (short tibia fibula).
an abnormally short tibia that has an unusual triangular shape. The tibia is the short triangular structure between the leg and the foot on the image below
and the unusual position of the sacrum which is almost horizontal.
The fetus after delivery. The triangular tibia, the mid face hypoplasia and the distal limb defects
and the X-rays demonstrates the platyspondyly.
- midface hypoplasia
- flattened nasal bridge
- small thorax
- horizontal sacrum
- triangular fibula and ulna
- talipes equinovarus.
At histopathology, lacunar halos are present around chondrocytes
The diagnosis could not be established prenatally but was established from the X-ray and pathology exam. The final diagnosis was: Neonatal Osseous Dysplasia also called Atelosteogenesis type II
Findings: Severe micromelia with ulnae and fibulae reduced to a triangular osseous remnant, clubbed humerus with proximal metaphyseal widening; irregular short curved radius, midface hypoplasia, spinal abnormalities, small thorax, talipes equinovarus and abducted thumbs and toes, platyspondyly, lumbosacral hyperlordosis or horizontal sacrum (3,4,5,6)
Laboratory abnormalities: Pathologic examination of cartilage shows lacunar halos around chondrocytes. Resting cartilage extremely abnormal; matrix attenuated with many cystic areas containing only radiating threads of matrix
Associated anomalies: Depressed nasal bridge, cleft palate, oligodactyly, clubfoot, short and bowed long bones, trachea or laryngeals anomalies, cervical kyphosis with hypoplastic and dysplastic changes of the spine.
Prognosis: Stillborn or neonatal death due to respiratory distress in all cases.
Management: Early ultrasound diagnosis allows pregnancy termination if opted by the parents, but a precise prenatal diagnosis of this lethal condition may be difficult.
OMIM : 256050
History: De la Chapelle et al. described an unrecognized skeletal dysplasia in a stillborn son and daughter of consanguineous parents. The limbs were strikingly short. The fibula and ulna were almost triangular. The middle phalanges were curiously double. Both had cleft palate and patent foramen ovale and ductus arteriosus. The boy had endocrine and hematologic abnormalities. A relationship of this skeletal dysplasia to mesomelic dwarfism of the hypoplastic ulna, fibula and mandible types (249700) has been suggested.
Differential diagnosis: (7,8,9,10,11,12,13,14,15,16,17)
most difficult with other types of Atelosteogenesis
Less shortening than type II,
· humerus: absent distal parts,
· femur: distally tapered
· fibula: absent
Marked shortening with widening of the metaphyses
· humerus: V or U shaped distal end
· femur: distal end rounded
· fibula: present in all cases
Club or globular humeri with precocious proximal epiphyseal ossification.
Absent fibula. (18)
All tubular bones hypoplastic and dysplastic with delayed mineralization
Tubular bones severe hypoplastic and dysplastic; second and third metacarpals and metatarsals larger than remaining bones
Harmonious ossification of tubular hand bones, bifid digits, Tombstone-shaped proximal phalanges, widened distal phalanges
Iliac bones almost round, irregular outline of iliac crest
Vertical block-like ischia
Incomplete ossification of vertebral bodies with coronal clefting
Cervical kyphosis with hypoplastic and dysplastic changes; lumbosacral
Segmentation defects in cervical spine with double curve (S) configuration,
Resting cartilage intact but hypocellular areas in which giant cells may be found. The proliferative and hypertrophic zone is shortened and distorted by prolongation of relatively acellular areas between the cell columns.
Resting cartilage extremely abnormal; matrix attenuated with many cystic areas containing only radiating threads of matrix.
Mild hypocellularity; otherwise normal.
Adapted from Atelosteogenesis, type I
1. De la Chapelle, A.; Maroteaux, P.; Havu, N.; Granroth, G. : Une rare dysplasie osseuse letale de transmission recessive autosomique. Arch. Franc. Pediat. 29: 759-770, 1972.
2. Hastbacka, J.; Wilcox, W. R.; Superti-Furga, A.; Rimoin, D. L.; Cohn, D. H.; Lander, E. S. : Atelosteogenesis type II is caused by mutations in the dystrophic dysplasia sulfate transporter gene (DTDST). Am. J. Molec. Genet. 57: A48 only, 1995.
3. Nores, J. A.; Rotmensch, S.; Romero, R.; Avila, C.; Inati, M.; Hobbins, J. C. Atelosteogenesis type II: sonographic and radiological correlation. Prenatal Diag. 12: 741-753, 1992.
4. Rossi, A.; van der Harten, H. J.; Beemer, F. A.; Kleijer, W. J.; Gitzelmann, R.; Steinmann, B.; Superti-Furga, A. : Phenotypic and genotypic overlap between atelosteogenesis type 2 and diastrophic dysplasia. Hum. Genet. 98: 657-661, 1996.
5. Salonen, R. : Neonatal osseous dysplasia I: second report. Prog. Clin. Biol. Res. 104: 171-172, 1982.
6. Sillence, D.; Kozlowski, K.; Rogers, J.; Sprague, P.; Cullity, G.; Osborn, R. Atelosteogenesis: evidence for heterogeneity. Pediat. Radiol. 17: 112-118, 1987.
7. Stern, H. J.; Graham, J. M., Jr.; Lachman, R. S.; Horton, W.; Bernini, P. M.; Spiegel, P. K.; Bodurtha, J.; Ives, E. J.; Bocian, M.; Rimoin, D. L. : Atelosteogenesis type III: a distinct skeletal dysplasia with features overlapping atelosteogenesis and oto-palato-digital syndrome type II. Am. J. Med. Genet. 36: 183-195, 1990.
8. Whitley, C. B.; Burke, B. A.; Granroth, G.; Gorlin, R. J. : De la Chapelle dysplasia. Am. J. Med. Genet. 25: 29-39, 1986.
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11. Jung C, Sohn C, Sergi C. Case report: prenatal diagnosis of diastrophic dysplasia by ultrasound at 21 weeks of gestation in a mother with massive obesity.Prenat Diagn. 1998 Apr;18(4):378-83.
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18. Taybi H. Radiology of Syndromes, Metabolic Disorders and Skeletal Dysplasias. 3er ed. Year Book Medical Publishers,Inc. 1990. pag. 689 -691