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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.

Prevalence: Rare

Etiology: Autosomal recessive inheritance (1)

Genetic: Mutation in the diastrophic dysplasia sulfate transporter gene (DTDST) (2)

Case report:

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.

Findings:

  • midface hypoplasia
  • micrognathia
  • flattened nasal bridge
  • small thorax
  • platyspondyly
  • horizontal sacrum
  • micromelia
  • 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)

  • atelosteogenesis I and III

  • fibrochondrogenesis

  • diastrophic dysplasia

  • mesomelic dwarfism of hypoplastic tibia

  • Nievergelt syndrome

 most difficult with other types of Atelosteogenesis

Type I

Type II

Type III

                                           Long bones
 
 

 

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)

                                           Hands/feet
 
 

 

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

                                         Pelvis
 
 

 

Nearly normal

Iliac bones almost round, irregular outline of iliac crest

Vertical block-like ischia

                                          Spine
 
 

 

Incomplete ossification of vertebral bodies with coronal clefting

Cervical kyphosis with hypoplastic and dysplastic changes; lumbosacral

hyperlordosis

Segmentation defects in cervical spine with double curve (S) configuration,

                                           Histopathology
 
 

 

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

References

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.

9.  Hastbacka J, Salonen R, Laurila P, de la Chapelle A, Kaitila I Prenatal diagnosis of diastrophic dysplasia with polymorphic DNA markers. J Med Genet. 1993 Apr;30(4):265-8.

10.  Kaitila I, Hastbacka J, de la Chapelle A, Sistonen P. [Defective gene causing diastrophic dysplasia has been localized]Duodecim. 1991;107(17):1418-9

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.

12.  Superti-Furga A. Achondrogenesis type 1B.J Med Genet. 1996 Nov;33(11):957-61. Review.

13.  Tennstedt C, Bartho S, Bollmann R, Schwenke A, Nitz I, Rothe K. [Osteochondrodysplasias. Prenatal diagnosis and pathological-anatomic findings] Zentralbl Pathol. 1993 Mar;139(1):71-80.

14.  Gembruch U, Niesen M, Kehrberg H, Hansmann M. Related Articles Diastrophic dysplasia: a specific prenatal diagnosis by ultrasound.Prenat Diagn. 1988 Sep;8(7):539-45.

15.  Gollop TR, Eigier A. Prenatal ultrasound diagnosis of diastrophic dysplasia at 16 weeks. Am J Med Genet. 1987 Jun;27(2):321-4.

16.  Kaitila I, Ammala P, Karjalainen O, Liukkonen S, Rapola J. Early prenatal detection of diastrophic dysplasia.Prenat Diagn. 1983 Jul;3(3):237-44.

17. Kaitila I, Ammala P, Karjalainen O, Liukkonen S, Rapola J. [Detection of diastrophic dysplasia in early pregnancy]Duodecim. 1983;99(14):861-8.

18. Taybi H. Radiology of Syndromes, Metabolic Disorders and Skeletal Dysplasias. 3er ed. Year Book Medical Publishers,Inc. 1990. pag. 689 -691

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