JMed Genet 1998;35:505-507 505 A lethal skeletal dysplasia with features of

chondrodysplasia punctata and osteogenesis J Med Genet: first published as 10.1136/jmg.35.6.505 on 1 June 1998. Downloaded from imperfecta: an example of Astley-Kendall dysplasia. Further delineation of a rare

Nursel Elqioglu, Christine M Hall

Abstract vault is unossified. The long are An unusual pre- extremely short, deformed, and appear frag- senting with lethal neonatal short limbed mented because of multiple ossification cen- , defective ossification, and tres. The tubular bones of the hands and feet punctate calcification within is are unossified. Multicentric ossification is also presented. The features resemble four present in the scapulae, pelvis, and facial cases previously described with Astley- bones. The vertebrae are less severely affected.3 Kendall dysplasia. Both HEM and DDD are severely hydropic.3 (3 Med Genet 1998;35:505-507) Keywords: osteochondrodysplasia; short limbed dwarf- Case report ism; lethal; Astley-Kendall dysplasia This stillborn female was delivered at 34 weeks' gestation. The Pakistani parents were young and healthy. No malformations or A review of 3500 cases on the Skeletal Dyspla- diseases were known to be present in the fam- sia Registry of the Department of Radiology, ily. Neither necropsy nor histochemical Great Ormond Street Hospital for Children examination of the cartilage was performed NHS Trust identified a fetus with striking and no photographs of the patient were radiological features resembling both chondro- obtained. dysplasia punctata and osteogenesis imper- fecta.

Astley-Kendall dysplasia is characterised http://jmg.bmj.com/ radiologically by absent ossification of the cra- nial vault and multifocal ossification giving a stippled appearance involving the axial skel- eton and carpus and tarsus. In addition, the ribs are short and deformed, the vertebral bod- ies flat, and the long bones short and deformed, with diaphyseal fractures and flared on September 29, 2021 by guest. Protected copyright. metaphyses.' Greenberg dysplasia (hydrops-ectopic calcification-motheaten skeletal dysplasia, HEM) has a poorly ossified vault, a frag- mented, "mottled" appearance of the long bones, most pronounced at their ends, but extending to involve the diaphyses.' Dappled diaphyseal dysplasia (DDD) has Department of more severe features than HEM. The skull Radiology, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK N Elgioglu* C M Hall

Correspondence to: Dr Hall.

*Present address: Department of Genetics, Cerrahpasa Medical School, Istanbul, Turkey. Received 5 August 1997 Figure 2 Babygram showing short, deformed limbs, short Revised version accepted for ribs with transverse defects, and multiple centres of increased publication bone density in the spine. Wormian bones are visible in the 3 December 1997 Figure 1 Lateral skull: absent ossification of the vault. skull. 5065E4ioglu, Hall

Table 1 Comparision of the radiologicalfindings of the present case with the reported Astley-Kendall cases and related conditions

Astley- Nairn-Chapman Present Dappled J Med Genet: first published as 10.1136/jmg.35.6.505 on 1 June 1998. Downloaded from Radiologicalfindings Kendall (aUl cases) case diaphyseal HEM Skull Lack of ossification of vault + + + + + Normal skull base + + + - - Spine Multiple dense centres (stippling) + + + + + Platyspondyly + + + + + Thorax Small + ++/ + + + Transverse translucent rib defects + + + + + Ribs deformed (wavy) + + + - + Ribs broad + ++/- + - - Scapulae subglenoid defect + + + - Pelvis Crescentic ilia + + + - - Limbs Short and deformed + + + + + Constriction and fracture near midpoint of long bones + + + Angulated tibia/fibula + + + Normal sized hands and feet + + + - - Stippled carpus/tarsus + + + + + Punctate epiphyses + ++/- + + + Splayed metaphyses + + + - + Multiple ossification centres of diaphyses - - - + + Severe hydrops - - - + + Pattern of inheritance AR AR AR AR

The postmortem radiographs show short, with a few transverse defects suggesting intra- deformed limbs and a narrow thorax with a uterine fracturing. Punctate calcification is moderately protuberant abdomen. In the skull present at the posterior ends of the ribs. The there is very poor ossification ofthe vault which scapulae have an unusual configuration with shows multiple wormian bone formation. The some deficiency laterally in the infraglenoid base of the skull and facial bones are well position. In the upper limbs, the long bones are developed (fig 1). short and bowed or angulated. The metaphyses In the spine, multiple areas of stippling are of the proximal humeri are flared. There are seen in the vertebral bodies in the lower radiolucent defects across the mid diaphyses of thoracic and lumbar regions and the pedicles the humeri with marginal sclerosis and callus and transverse processes thoughout. There is indicating healing fractures. Stippling is marked platyspondyly and absent ossification present in the carpus (fig 2). of vertebral bodies in most of the thoracic In the pelvis, the iliac wings are wide, short, http://jmg.bmj.com/ region with only a trace of ossification at the and concave inferiorly (crescentic). There is levels ofD 1 and D2. The thorax is narrow with extensive stippling affecting the pubic bones short, broad, spatulate ribs widened at the and ischia. Stippling is also present in the anterior ends. The ribs are deformed (wavy) upper femoral regions and extensively through- out the tarsus. There is expansion owing to callus with some sclerosis of the diaphyses of

both femora and transverse lytic areas repre- on September 29, 2021 by guest. Protected copyright. senting fracturing. The distal metaphyses and epiphyses are well maintained. The tibiae and fibulae are extremely short and angulated. In the feet, the short tubular bones are well devel- oped with no evidence of deformity (fig 3).

Discussion This stillborn infant shows a number of features reminiscent of several conditions. In particular, the poor ossification in the cranial vault, transverse defects in the diaphyses of long bones with surrounding callus and sclero- sis, angulated tibiae, and broad ribs are features seen in . Stippling is a feature of all forms of chondrodysplasia punc- tata and of other disorders.4 In this case the combination offindings is diagnostic ofAstley- Kendall dysplasia. Astley and Kendall' described a stillborn infant and Nairn and Chapman5 reported another three female sibs from a consanguine- ous marriage with this condition. However, there have been suggestions published6 that Figure 3 Lower limbs and pelvis showing crescentic ilia, stippled ischia, short, deformedfemora with wide diaphyses, these sibs had features of DDD and not Astley- and angulated tibiae/fibulae. Kendall dysplasia. It has also been suggested Astley-Kendall dysplasia 507

that HEM represents a milder form ofDDD.6 cases of this presumed autosomal recessive dis- We feel that Astley-Kendall dysplasia is distinct order, interestingly, have occurred in Asians

from both DDD and HEM on radiological from the Midlands area of the United King- J Med Genet: first published as 10.1136/jmg.35.6.505 on 1 June 1998. Downloaded from grounds (table 1). dom. The chondro-osseous morphology ofAstley- Kendall dysplasia has been well described.7 1 Astley R, Kendall AC. A bone dysplasia for diagnosis. Ann There is dystrophic globular calcification Radiol 1980:23:121-3. within 2 Greenberg CR, Rimoin DL, Gruber HE, DeSa DJB, Reed epiphyses, vacuolated chondrocytes, M, Lachman RS. A new autosomal recessive lethal widened lacunae, and disorganised growth with congenital hydrops. Am Med Genet 1988;29:623-32. plate with irregular columns, maturational 3 Carty H, Kozlowski K, Sillence D. Dappled diaphyseal arrest, and thin cortex. Fractures of the dyplasias. Fortschr Rontgenstr 1989;150:228-9. 4 Poznanski AK. Punctate epiphyses: a radiological sign not a diaphyses were present with fibrous tissue pro- disease. Pediatr Radiol 1994;24:418-24. liferation and callus formation. The chondro- 5 Nairn ER, Chapman S. A new type of lethal short-limbed dwarfism. Pediatr Radiol 1989;19:253-57. osseous morphology of HEM is significantly 6 Spranger J, Maroteaux P. The lethal osteochondrodyspla- different.2 sias. Adv Hum Genet 1990;19:1-102. case represents 7 Taybi H, Lachman RS. Radiology ofsyndromes, metabolic dis- Our the fifth published orders, and skeletal dysplasias. 4th ed. St Louis: Mosby, report of Astley-Kendall dysplasia. To date, all 1996:838-9. http://jmg.bmj.com/ on September 29, 2021 by guest. Protected copyright.