Spondylometaphyseal Dysplasia–Sedaghatian Type

Nursel Elcioglu2 and Christine M. Hall1*1Department of Radiology, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom2Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Turkey

We present the radiological findings in twounrelated cases with spondylometaphy-seal dysplasia type Sedaghatian. We reviewthe literature and identify additionalanomalies including disproportionatelylong fibulae, dysharmonious maturationand turricephaly. Am. J. Med. Genet. 76:410–414, 1998. © 1998 Wiley-Liss, Inc.

KEY WORDS: lethal chondrodysplasia;platyspondyly; metaphysealdysplasia; Sedaghatian dys-plasia; AR inheritance

INTRODUCTION

Spondylometaphyseal dysplasia type Sedaghatian isa rare, perinatally lethal osteochondrodysplasia com-prising minor facial, cardiac and cerebral anomalies,rhizomelic shortness of long bones, metaphyseal cup-ping and irregularity, platyspondyly, delayed epiphy-seal ossification, irregular ‘‘lacy’’ iliac crests, andbrachydactyly. To date eight cases have been reportedin four families; seven of them boys. The condition ispresumed to be inherited in an autosomal recessivemanner.

The radiological findings in a further two unrelatedmales are compared with the five other cases illus-trated in the literature.

CLINICAL REPORTSCase 1

Fetus A.H. (male) was the second pregnancy of ayoung healthy non-consanguineous Pakistani couple,the first having resulted in the birth of a normaldaughter. During this pregnancy, the limbs werethought to be short on US examination at 31 weeks andthis was confirmed at 33 weeks gestation. The babywas stillborn at 36 weeks with a birthweight of 2.9 kg(75th centile), length of 43 cm (2nd centile), and head

circumference (OFC) of 31 cm (10th centile). Photo-graphs of the baby showed only rhizomelic shortness.

X-ray examination showed some overriding of the su-tures, a large posterior fontanelle, and a disproportion-ately small occipital bone. There was an appearance ofturricephaly with elevation of the parietal bones. Themandible appeared large with some straightening ofthe mandibular angle. There was ossification of thehyoid bone (Fig. 1a). The long bones were short withmildly flared metaphyses. The metaphyses were alsoextremely irregular and with marginal sclerosis. In ad-dition, there was disproportionate shortness of thetibiae, the fibulae being relatively long (Fig. 1b). Theribs were short; 12 pairs were present. There was pro-nounced cupping of the medial and lateral ends of theribs. The scapulae showed an irregular contour andthere was lateral spiking in the region of the inferiorangles. There was abnormal ossification of the iliacwings. The wings were short but wide laterally withrelatively prominent anterior inferior spines. Therewas a medial extension of the iliac wings towards thesacrum and a groove extending along the iliac crests.The acetabular roofs were horizontal with medial andlateral spurs. The sacrosciatic notches were wide. Theischia showed irregular ossification with a notched ap-pearance superiorly. There was generalised platyspon-dyly, evident on the anterio-posterior views (Fig. 1c).Unfortunately no lateral view was available.

Case 2

Baby A.K. (male) survived until age 6 weeks. Thiswas an isolated case, the child being of young healthyunrelated Middle-East parents. His birth length was43 cm (<0.4th centile). He had been asphyxiated afterfetal distress and had been ventilated since birth. Hehad continuous seizures until death. His hands andfeet had an unusual position and redundant skin foldswere noted in the limbs. An ultrasound scan of hisbrain showed porencephaly. Unfortunately neither au-topsy nor clinical photographs were obtained.

By using X-ray examination, a skeletal survey at age6 weeks showed an extremely large posterior fontanelleand unusually small occiput, giving an appearance ofturricephaly (Fig. 2a). The ribs were short with markedcupping posteriorly and anteriorly. There were 11 pairsof ribs. The scapulae showed irregular ossification andthe inferior angles were deficient with lateral spiking(Fig. 2b). In the spine, there was generalised platy-spondyly (Fig. 2c). The iliac wings were short but rela-

*Correspondence to: Dr. Christine M. Hall, Department of Ra-diology, Great Ormond Street Hospital for Children NHS Trust,London WC1N 3JH, United Kingdom.

Received 11 August 1997; Accepted 21 November 1997

American Journal of Medical Genetics 76:410–414 (1998)

© 1998 Wiley-Liss, Inc.

tively broad with prominent anterior superior iliacspines. There were grooves along the length of the iliaccrests, giving a double edged appearance, and therewas medial extension of the iliac wings towards thesacrum. The acetabular roofs were horizontal with pro-nounced medial spurs and small sacrosciatic notches.The ischia have irregular ossification with superior de-fects (Fig. 2d). The long bones were short. The metaph-yses were mildly flared with cupping, irregularity, andmarginal sclerosis. The fibulae were disproportionatelylong. The epiphyses adjacent to the knees were smallfor age and were indistinct and irregular. The tarsalbones showed very irregular ossification, giving the ap-pearance of stippling. The calcaneum was relatively

large and showed multiple ossification centres (Fig.2e). There was significant shortness of all metacarpalsand phalanges. There were pseudo-epiphyses at thedistal end of the 1st metacarpal and the proximal endsof the 2nd and 3rd metacarpals. The metaphyses of themiddle and proximal phalanges were cupped and thereappeared to be probable early ossification of cone-shaped epiphyses of the proximal and middle phalan-ges. However, there was no ossification of any carpalcentres at this stage. There also appears to be earlyossification of an epiphysis at the distal end of the hu-merus (Fig. 2f). The radiological findings of our two,together with the five cases illustrated in the litera-ture, are presented in Table I.

Fig. 1. A,B,C: Case 1 at 36 weeks of gestation. A: Lateral skull andcervical spine: elevated parietal bones. B: Lower limbs and pelvis: irregularsclerotic metaphyses, horizontal acetabula, and medial extensions of ilia.C: Chest: cupped ribs, platyspondyly, and spiked angles of scapulae.

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DISCUSSION

In 1980, Sedaghatian described in two brothers anda sister a neonatally lethal disorder associated withslight rhizomelic limb shortness, mild platyspondyly,severe metaphyseal dysplasia, and ‘‘laciness’’ of theiliac wings. Subacute myocarditis, cortical necrosis ofthe kidneys, and adrenal and pulmonary hemorrhagewere the autopsy findings of one of the boys. Labora-tory test showed low calcium, high phosphate, and highalkaline phosphatase; however these abnormalitieswere thought to be due to a renal defect. Spranger and

Maroteaux [1990] reviewed the radiological findingsand illustrated also platyspondyly in the original pa-tient. In 1987 Opitz et al. described another infant witha similar perinatal course and radiological findings, al-though the radiographs were not illustrated. This in-fant was born to first cousins, suggesting an autosomalrecessive single gene defect. In 1992, Peeden et al. re-ported another case with ASD and lissencephaly andindicated that the limb shortness cannot be detecteduntil 30 weeks of gestation.

Campbell et al. indicated that the limb shortnesscannot be detected until 30 weeks gestation. Campbell

Fig. 2. A–F: Case 2 age 6 weeks. A: Lateral skull and cervical spine: small occiput and elevated parietal bones. B: Chest: cupped anterior and posteriorribs, deficient scapular angles. C: Lateral spine: platyspondyly throughout. D: Pelvis: grooved iliac wings, notched ischia. E: Lower limbs: irregularsclerotic metaphyses, disproportionately long fibulae. F: Left upper limb with cupped irregular metaphyses, phalangeal and metacarpal cone-shapedepiphyses, and pseudo-epiphyses.

412 Elcioglu and Hall

et al. [1992] reported the radiological changes of twofurther cases and highlighted that the alkaline phos-phatase levels are normal in this condition. Their re-view of antenatal US examinations showed the limbmeasurements to be in the low normal range at 19weeks of gestation and that the growth rate declined inthe third trimester. Several of the cases were of Iranianorigin, but Peeden et al. reported findings in a blackAmerican infant and Campbell et al. [1992] reportedtwo affected sibs to an English, Caucasian unrelatedcouple.

The chondro-osseous morphology is well described byOpitz et al. [1987], Peeden et al. [1992], and Campbellet al. [1992]. There are epimetaphyseal changes some-what similar to those in hypophosphatasia. The char-acteristic findings include poor polarization of bone, de-ficient lamellar formation, long hypertrophic zone withdense cells, and little matrix extending into the me-taphysis with lack of remodelling. The alkaline phos-phatase level in all these cases was normal althoughone of the sibs in the original Sedaghatian report had a

high alkaline phosphatase level (probably explained byrenal failure).

Redundant skin folds, present in our case 2, werealso noted over the limbs of the case of Peeden et al.[1992]. Minor and other morphological abnormalitieswere noted in the only girl reported, the sister of twoaffected males. She was described as having microph-thalmia, asymmetry of ears, depressed nasal bridge,broad nose, short neck, and prominent sternum. Oneaffected brother had micrognathia, a depressed nasalbridge, and low-set, posteriorly angulated ears[Sedaghatian, 1980]. Other minor anomalies in thecase of Peeden et al. [1992] of black American back-ground included a flat nasal bridge, telecanthus,beaked nose with anteverted nostrils, short neck, andsimple, posteriorly angulated ears.

Intracranial abnormalities consisting of poren-cephaly were present in our case 2. The case of Peedenet al. [1992] on CT scan and at autopsy was found tohave a reduced gyral pattern and focal lissencephaly.

Table I demonstrates that all seven cases have platy-

Fig. 2. (Continued).

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spondyly and short long bones, including those of thehands, with metaphyseal cupping and mild flare andirregularity. The ribs are cupped anteriorly and poste-riorly. The changes in the pelvis and tarsal bones werecommon to all. All cases demonstrated a disproportion-ately long fibula. Turricephaly was present in fourcases. The chest was narrow or small in three cases andtwo had 11 pairs of ribs. Delayed ossification of theepiphyses around the knees was present in all cases,but interestingly, probable advanced ossification ofhand and elbow epiphyses was identified in our Case 2and there was premature ossification of the hyoid bonein our Case 1.

Radiological differentiation is required from other le-thal and perinatally lethal conditions with severeplatyspondyly. In thanatophoric dysplasia and thethanatophoric variants (the lethal platyspondylicgroup), the thorax is severely narrow as a result of thesevere shortness of the ribs. Hand and pelvic abnor-malities are also different. The lethal metatrophic dys-plasias have marked platyspondyly but are differenti-ated on the basis of marked metaphyseal flaring result-ing in bulbous ends of the long bones.

Thus the age of presentation, clinical course, andspecific radiological changes enable the diagnosis of

spondylometaphyseal dysplasia type Sedaghatian to beestablished with certainty. Additional findings identi-fied include disproportionately long fibulae, dysharmo-nious maturation and turricephaly.

ACKNOWLEDGMENTS

We thank Dr. B. Kerr and Dr. N. Cavanagh for refer-ral of the patients.

REFERENCES

Campbell RSD, Ireland M, Bloxham CA, Chippindale (1992): Platyspon-dylic lethal osteochondrodysplasia: Shiraz type with radiological patho-logical correlation. Pediatr Radiol 22:90–92.

Opitz JM, Spranger JW, Stoss HR, Pesch H-J, Azadeh B (1987): Sedagha-tian congenital lethal metaphyseal chondrodysplasia: Observations ina second Iranian family and histopathological studies. Am J Med Genet26:583–590.

Peeden Jr JN, Rimoin DL, Lachman RS, Dyer ML, Gerard D, Gruber HE(1992): Spondylometaphyseal dysplasia, Sedaghatian type. Am J MedGenet 44:651–656.

Sedaghatian MR (1980): Congenital lethal metaphyseal chondrodysplasia:A newly recognized complex autosomal recessive disorder. Am J MedGenet 6:269–274.

Spranger J, Maroteaux P (1990): The lethal osteochondrodysplasias. AdvHum Genet 19:1–103.

TABLE I. Radiological Findings of Previously Reported Cases (Illustrated) Compared With Our Cases

Sedaghatian Campbell et al. Our cases

Case 1 Case 2 Peeden et al. Case 1 Case 2 Case 1 Case 2

Sex M M M M M M MSib occurrence + + − + + − −X-ray abnormalitiesShort long bones + + + + + + +Metaphyseal cupping/flaring/irregularity + + + + + + +Epiphyseal ossification

Delayed + + + + + + +Advanced +

ChestSmall, narrow + − − − − + +Cupped ribs + + + + + + +11 pair of ribs − − + − − − +

Platyspondyly + + + + + + +Pelvis

Flared iliac wings + + + + + + +Horizontal acetabular roofs + + + + + + +Lacy iliac crest + + + + + + +Ischia irregular (sup. ± inf.) + + + + + +

Fibula disproportionately long + + + + + + +Hands and feet

Brachydactyly + + + + + + +Metaphyseal cupping + + + + + + +Tarsal bones irregular + + + + + +

Turricephaly + + − − + +US prenatal/short limbs 33 wks − 3d trimester 31 wks −

414 Elcioglu and Hall