Figure 4: X-ray of the fetus.
The thorax appeared relatively small and bellâshaped. Most striking were the short and distally tapered humori and femora. There was bowing of the ulnae, the radii, the tibias and absence of the fibulae. The distal phalanges of the fingers were ossified, but there was no mineralization of the ossification centers of the middle and proximal phalanges. The distal and proximal phalanges of the toes were partly mineralized. The feet were in severe equinovarus position. The pelvis showed rounded iliac bones, flat acetabulae and unossified pubic bones.
No definite abnormalities of the skull were noted. Histologic study of the cartilage showed an intact reserve zone with hypocellular areas interspersed with areas of normal cellularity with a few giant cells.
The growth plate showed a narrow hypertrophic zone and irregular column formation.
Based on radiologic and histologic findings, the diagnosis of atelosteogenesis type I was made.
Discussion
In table I, some radiographic and histopathologic differences between atelosteogenesis type I and type II are presented based on the data of Sillence and Kozlowski8.
Atelosteogenesis type II can be distinguished from type I by radiographic and histopathologic criteria. The dysplastic ossification pattern in type I and type II is similar.
Due to insufficient radiologic and histopathologic documentation, not all earlier presented cases1â7 of atelosteogenesis can be reclassified as type I or type II.
An ultrasonographic and clinical marker for atelosteogenesis type II is the unusually wide space between first and second digit of both hands and feet (hitchhiker thumb or toe). In the fetus described above we saw small broad hands and broad feet with normal position of fingers and toes. Remarkable were the echodense fingertips. These echodense structures were the only bones, terminal phalanges, in the hands with mineralized ossification centers. Ossification of the terminal phalanges (hands) starts between 11 and 12 weeks of gestation and can be observed by ultrasound between 12 and 13 weeks. Within the next two weeks the midâ and proximal phalanges are mineralized14 . The process of mineralization in the present fetus probably went wrong around 12 weeks of gestation.
Table 1: Radiographic and histopathologic differences between atelosteogenesis type I and type II8
Type I
|
Type II
|
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
|
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
|
Pelvis
|
Nearly normal
|
Iliac bones almost round, irregular outline of iliac crest
|
Spine
|
Incomplete ossification of vertebral bodies with coronal clefting
|
Cervical kyphosis with hypoplastic and dysplastic changes; lumbosacral hyperlordosis
|
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.
|
Etiology
In contrast to atelosteogenesis type I, autosomal recessive inheritance of type II is suggested by parental consanguinity11 and by recurrence of this disorder in a subsequent pregnancy6,8,12 . All cases of atelosteogenesis type I have been sporadic in otherwise normal families without consanguinity.
According to Hunter and Carpenter13 atelosteogenesis type I, II and III have different radiologic and histopathologic appearances Still, more cases must be studied before it can be stated with certainty6 that they are distinct conditions.
Ultrasound diagnosis
The inutero diagnosis of atelosteogenesis is unusual. The diagnosis is based primarily on the radiographic appearance of the spine, long bones and hands and histopathologic study of the growth cartilage.
Recently, Nores et al.12 described a case of atelosteogenesis type II prenatally diagnosed at 15 weeks of gestation. A previous pregnancy of the same patient was terminated at 22 weeks of gestation because of severe micromelia, spinal abnormalities, talipes equinovarus and abducted thumbs and toes. At postâmortem examination, atelosteogenesis type II was diagnosed.
The ultrasound diagnosis of atelosteogenesis type II is probably easier than that of type I because of the suggested autosomal recessive inheritance.
References
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2. Maroteaux P, Spranger J, Stanescu V, et al. Atelosteogenesis. Am J Med Genet 13: 15â25, 1982.
3. Sillence DO, Lachman RS, et al. Spondylohumerofemoral hypoplasia (Giant cell chondrodysplasia): a neonatally lethal shortâlimb skeletal dysplasia. Am J Med Genet 13: 7Ââ14, 1982.
4.Yang SS, Roskamp J, et al. Two lethal chondrodysplasias with giant chondrocytes. Am J Med Genet 15: 615â625, 1983.
5. Kozlowski K, Bateson EM. Atelosteogenesis. ROEFO 140: 224â225, 1984.
6.McAlister WH, Crane JP, et al. A new neonatal short limbed dwarfism. Skeletal Radiol 13:271â275, 1985.
7. Chervenak FA, Isaacson G, et al. Antenatal diagnosis of frontal cephalocele in a fetus with atelosteogenesis. J Ultrasound Med 5: 111â113, 1986.
8. Sillence DO, Kozlowski K, et al. Atelosteogenesis: evidence for heterogeneity. Pediatr Radiol 17: 112â118, 1987.
9. Herzberg AJ, Effmann EL, Bradford WD. Variant of atelosteogenesis? Report of a 20âweek fetus. Am J Med Genet 29: 883â890, 1988.
10. Stern HJ, Graham JM, Lachman RS, et al. Atelosteogenesis type Ill: a distinctive skeletal dysplasia with features overlapping atelosteogenesis and otoâpalatoâdigital syndrome type 11. Am J Med Genet 36: 183â195, 1990.
11. Temple K, Hall CA, et al. A case of atelosteogenesis. J Med Genet 27: 194â197, 1990.
12. Nores JA, Rotmensch S, Romero R, et al. Atelosteogenesis type 11: sonographic and radiological correlation. Prenat Diagn 12:741â753, 1992.
13. Hunter AGW, Carpenter BF. Atelosteogenesis I and boomerang dysplasia: a question of nosology. Clin Genet 39: 471â480, 1991.
14. Brons JTJ,van der Harten HJ. Skeletal dysplasias â Preâ and postnatal identification. An ultrasonographic, radiologic and pathologic study, Academic Thesis "All inâ⏠BV, Amsterdam, 1988.
15. Romero R, Pilu G, Jeanty P, et al. Prenatal diagnosis of congenital anomalies. Appleton & Lange, p. 340â341, 1988.
16. Buyse ML, MD. Birth Defects Encyclopedia, Blackwell Scientific Publications, p. 207â208, 1990.