Spondylometaphyseal Dysplasia: Sedaghatian Type

Ayman Koutouby,* Javed Habibullah, and Faquih Arif MoinuddinDepartment of Pediatrics, Al Wasl Maternity and Pediatric Hospital, Department of Health and Medical Services,Government of Dubai, United Arab Emirates

We report a case of spondylometaphysealdysplasia in an infant who was born to non-consanguineous Yemeni parents. Radiologi-cal findings were consistent with lethal me-taphyseal chondrodysplasia (Sedaghatiantype). Although all previously reportedcases died within 4 days of life, our patientsurvived 161 days. This reported case wasthoroughly investigated for serum calcium,magnesium, zinc, ammonia, phosphatelevel, alkaline phosphatase, parathormonelevel, liver and renal function test, TORCH,metabolic screening, skeletal survey, chro-mosomal studies, muscle enzymes, EEG,computed tomography scan, and magneticresonance imaging (brain). Genomic DNAanalysis of patient and parents were sent tothe Faculty de Medicine Xavier Bichat,France, but yet abnormal gene could not bedetected. Am. J. Med. Genet. 90:199–202,2000. © 2000 Wiley-Liss, Inc.

KEY WORDS: spondylometaphyseal dys-plasia; congenital lethal me-taphyseal chondrodysplasia(Sedaghatian type); platy-spondylic lethal osteochon-drodysplasia (Shiraz type);epimetaphyseal chondrodys-plasia; autosomal recessiveinheritance

INTRODUCTION

Congenital lethal metaphyseal chondrodysplasiawas first described by Sedaghatian [1980] in three sibs(two brothers and one sister) of nonconsanguineousIranian parents. Since then nine cases in six familieswere reported. This syndrome is also known as spon-dylometaphyseal dysplasia or platyspondylic lethal os-teochondrodysplasia (Shiraz type) and comprises nor-

mal intrauterine growth, narrow rib cage, rhizomelicshortness of limbs, slight platyspondyly, and severemetaphyseal dysplasia. All previously described in-fants died shortly after birth. Autopsy performed in oneshowed subacute myocarditis, pulmonary hemorrhage,cortical necrosis of kidneys, and adrenal. We report ourfindings in an Yemeni infant with similar radiologicalfindings who survived for 161 days.

CLINICAL REPORT

A term male infant was delivered normally with Ap-gar scores of 5 after one minute and 6 after 5 minutesto a 28-year-old gravida 3, para 2 mother. Both parentsare Yemeni and nonconsanguineous. Two older chil-dren (one male and one female) were normal. Motherwas 160 cm tall and weighed 60 kg. Father was 170 cmtall and weighed 65.6 kg, and he had seven healthy sibs(four male and three female). Neither parent had anyIranian relatives. Family history was unremarkable.

The infant’s birth weight was 3,485 kg, head circum-ference 34.5 cm, and length 45 cm. Soon after birth hehad low hairline, mild hypertelorism, short neck, fron-tal bossing, retrognathia, broad hands, and shortlimbs. His upper to lower body segment ratio was 1.5:1.0. The eyes were normal and so were nose, palate,lips, and philtrum. The chest was narrow; there was agrade II/VI soft ejection systolic murmur at the leftlower sternal border. Abdomen was soft with liver pal-pable 3 cm below the right costal margin. There wereno other palpable abdominal masses. Genitalia werenormal. The anus was patent. The back appeared nor-mal. Infant was profoundly hypotonic, hyporeflexicwithout any spontaneous movements (Fig. 1A). Me-chanical ventilation was needed because of impendingrespiratory failure. At age 10 hours infant was noted tohave generalized tonic and clonic seizures (with asso-ciated desaturation). The patient was fully investi-gated for probable septicemia, metabolic disorders,anatomic brain lesions, congenital heart defects,muscle enzymes, liver and renal function tests,TORCH, chromosomal analysis, amino acid, and sugarchromatography. Echocardiogram showed atrial septaldefect (ASD) secundum defect. The infant’s seizure ac-tivity could not be controlled effectively despite mul-tiple anticonvulsant medications including a trial ofintravenous pyridoxine. He never acquired the abilityto breathe on his own, hence continued to require re-spiratory support till his death on day 161. Biopsies

*Correspondence to: Dr. Ayman Koutouby, Consultant Neona-tologist, Al Wasl Maternity & Pediatric Hospital, P.O. Box 9115,Dubai, United Arab Emirates.

Received 14 May 1999; Accepted 30 September 1999

American Journal of Medical Genetics 90:199–202 (2000)

© 2000 Wiley-Liss, Inc.

(muscle and bone) and autopsy were refused by theparents.

RADIOLOGICAL FINDINGS

The skeletal survey showed striking radiologicalchanges. The metaphyses were cupped, irregular, andmildly flared. The long bones were all short (Fig. 1C).In the hands there were shortness of metacarpals andphalanges with cone shaped epiphysis. In the spinethere was generalized platyspondyly. The thorax wasnarrow with rather short ribs, which were cupped an-teriorly and posteriorly. The ribs showed V-shaped bor-der at the posterior ends and flattening at the anteriorends (Fig. 1D). The tarsal bones showed very irregularand somewhat stippled ossification. In the pelvis, theischia had irregular ossification. The iliac crests had adouble-edged appearance, which is typically calledlace-like appearance. These findings were all consis-tent with the diagnosis of spondylometaphyseal dys-plasia type Sedaghatian. The skull vault did not showany significant abnormalities. Bone age correlated tothe chronological age.

The skeletal survey was repeated at different ages

with the last one being done at age 138 days. The find-ings remained unchanged except increasing evidence ofdiffuse osteopenia and irregular mineralization at themetaphysis of tubular bones.

OTHER INVESTIGATIONS

Electroencephalogram done at age 3 weeks showed acouple of essentially left-sided discharges of highervoltage associated with focal sharp waves mixed withlarge delta waves. Abdominal ultrasound was normal.Computed tomography scan of brain showed normalanatomy with abnormal low density in the convexitycortex in the lateral frontal parietal and posterior tem-poral regions. Magnetic resonance imaging scan ofbrain at age 24 days showed damage effecting the con-vexity cortex. The underlying white matter was notmyelinated (Fig. 1B). Other laboratory findings areshown in Table I.

DISCUSSION

This case showed marked similarity with Sedagha-tian lethal metaphyseal dysplasia, which has been re-

Fig. 1. A: Patient with profound hypotonia. B: MRI (brain) showing grossly abnormal cortical development. The underlying white matter is notmyelinated. C: The metaphyses are cupped, irregular with mild flare and short long bones. D: The ribs have a ‘V’ shaped border at the posterior ends.

200 Koutouby et al.

ported in two Iranian families [Sedaghatian, 1980;Opitz et al., 1987], one British Caucasian [Campbell etal., 1992], one Black American [Peeden et al., 1992],one Pakistani, and one Middle-Eastern parents [Elcio-glu and Hall, 1998]. So this complex dysplasia is notconfined to people of Iranian or Middle-Eastern originas suggested initially [Opitz et al., 1987].

The parents of the patient described herein are Ye-meni and not consanguineous. Of 10 cases reported (in-cluding our case), nine were male, which shows thatmetaphyseal dysplasia predominantly occurs in males.In 1990, Spranger and Maroteaux [Elcioglu and Hall,1998] reviewed the radiological findings and illustratedalso platyspondyly in the original patient.

The roentgenographic features of long bones, i.e.,shortening metaphyseal dysplasia, mild platyspondyly,pelvic abnormalities, and cupping of rib ends are allcomparable with the Shiraz cases. Our case survivedfor 161 days and may be the longest live case of lethalmetaphyseal dysplasia to date. This proves that thecourse of this disease may not be as fatal as rapidlyclaimed previously.

The striking feature of our case was intractable con-vulsions, which could not be controlled effectivelyby multiple anticonvulsant drugs. We do agreewith Peeden et al. [1992] that abnormal neurologi-cal findings suggested involvement of central ner-vous system as our patient had abnormal electroen-cephalogram, brain computed tomography scan, andmagnetic resonance imaging. This reported case re-mained completely hypotonic without any spontaneousrespiratory efforts and needed mechanical ventilationthroughout his life. Perhaps the neurological abnor-malities and patient’s apnea were major causes ofdeath.

TABLE I. Laboratory Findings

Investigation Results

Serum calcium 2.38 mmol/LSerum magnesium 9 mmol/LSerum zinc 23 mmol/LSerum parathormone 410 ng/LSerum inorganic phosphate 1.6 mmol/LSerum alkaline phosphatase 120 U/LSerum lactate dehydrogenase 120 U/LSerum creatine kinase 2 70 U/LSerum ammonia 29.3 mmol/LBlood urea nitrogen 1.2 mmol/LSerum creatinine 28 mmol/LSerology test for: toxoplasmosis,

rubella, CMV, herpes, & parvovirusNegative

Blood & urine for amino acid andsugar chromatography

Negative

Liver function test NormalChromosomal analysis (infant & parents) NormalGenomic DNA analysis No abnormality

detected to date

Fig. 1. (Continued).

Spondylometaphyseal Dysplasia 201

Our patient had persistently low blood urea, creati-nine, and uric acid without apparent explanation,which has not been reported before. Other metabolicand biochemical investigations were all normal. Intra-uterine infections were ruled out by negative serologyfor TORCH and Parvovirus.

ACKNOWLEDGMENTS

We thank Prof. Salah El-Kalla, Head of the PediatricDepartment, Department of Health & Medical Ser-vices, Dubai and Dr. Caroline Silve from the Faculte deMedicine Xavier Bichat, France, for their cooperationin genomic DNA analysis of the patient and his par-ents. We also thank Dr. M.R. Sedaghatian, Consultantand Head of the Neonatal Department, Al Mafraq Hos-pital, Abu Dhabi, for his expert opinion and Mrs. Phi-lomena Barneto for secretarial assistance.

REFERENCES

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

Elcioglu N, Hall CM. 1998. Spondylometaphyseal dysplasia: Sedaghatiantype. Am J Med Genet 76:410–414.

Opitz JM, Spranger JW, Stoss HR, Pesch HJ, Azadeh B. 1987. Sedaghatiancongenital lethal metaphyseal chondrodysplasia: observation in a sec-ond Iranian family and histopathological studies. Am J Med Genet26:583–590.

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

Sedaghatian MR. 1980. Congenital lethal metaphyseal chondroplasia: anewly recognized complex autosomal recessive disorder. Am J MedGenet 6:269–274.

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

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