Med. J. Malaysia Voi. XXXV No. 1, September 1980

LETHAL NEONATAL : A CASE OF

MASOOD K AFZAL CHOO KENG EE SUMMARY pregnancy, she had one previous abortion. Three other children are alive and well. The parents are Achondrogenesis is a lethal neonatal chondro­ well and healthy. There was no history of dysplasia with extreme micromelia and marked congenital abnormalities. There was no antenatal discrepancy between the relatively large head and history of drugs or illness. The baby was the decreased trunk length. The affected neon­ delivered gasping and died shortly afterwards. At ates are usually delivered prematurely, and are birth the baby weighed 2 lb 8 oz and the Apgar stillborn or die soon after birth. Polyhydramnios was 2 at 1 min. The neonate had a dispropor­ is frequently present. It is an inherited autosomal tionately large head, short neck, distended recessive disease. The radiographic features are abdomen. thorax and reduction deformities of all diagnostic. limbs. The baby was markedly oedematous, (Fig. 1). Head circumference was 28.5 cm, crown­ INTRODUCTION rump length 20 cm and crown-heel length 25 cm. The thoracic circumference at the nipple was 21 OUR interest in neonatal dwarfism was aroused cm. Post-mortem of the baby was not granted by the presentation of a deformed neon ate with and we were also unable to obtain blood for short upper limbs and flapper-like lower limbs. chromosomal and viral studies. We were unable to diagnose that baby. That was three years ago, since then we have seen one case The radiographic features in this neonate are of short rib polydactyly syndrome, one case of seen in Fig. 2. There is absent ossification of the chondrodysplasia puncta or Conradi's disease and lumbar vertebrae and sacrum. The ischium and one of neonatal . Our most recent pubic are also unossified. The iliac bones addition is a case of achondrogenesis which we are small with concave inner and inferior present here. The aim of this article is to alert margins. The tubular bones are markedly short­ paediatricians and obstetricians of neonatal dwar­ ened and show metaphyseal widening and fism so that genetic counselling to parents can be cupping. The thorax is small and barrel-shaped. done. More often than not, in pratice, such the ribs are short. The small non-ventilated babies are diagnosed as "still birth", "preterm thoracic cage contrasts with the bulging abdo­ baby with congenital deformities" or "preterm men. The skull shows good ossification and with ". appears very large in comparison with the marked shortening of trunk and limbs. CASE REPORT The clinical and radiographic features in this newborn baby are characteristic of Achondro­ A baby girl was prematurely delivered at 28 genesis type 2(Langer-Saldino-Fraccara). The weeks gestation on 18.10.1979 to a thirty-year-old absent ossification of the lumbar vertebrae, mather (K bt. A.H.). This was her fourth sacrum, ischium and pubis with the characteristic Masood K. Afzal, MBBS, DMRD, small iliac bones with concave inner and inferior Radiologist, University Hospital, University of margins (Fig. 3) are diagnostic of achondrogene­ Malaya, Kuala Lumpur. sis. The normal ossification of the skull and the Choo Keng Ee*, MBBS, MRCP (UK) radiographic appearance of the limbs are features Paediatrician, General Hospital, Seremban consistent with type 2 (Yang, 1974). The abnor­ *Presently, Paediatrician, General Hospital, Kuala mality in type 2 appears to affect and Trengganu. tubular bones but not membraneous bones.

64 Fig.I Photograph of achondrogenlc newborn showing large head, short thick trunk and marked micromelia.

Fig. 2 Achondrogenesise anterior and lateral radiographs showing non-ossification of vertebrae and pelvic bones; Fig. 3 Close-up view of pelvis showing the typical small ilia small ilia with concave inner and inferior margins; with concave inner and inferior margins which is small thorax with short ribs; prominent abdomen and diagnostic of achondrogenesls, large head with normal ossification of skull, The tubular bones of the limbs are short and show characteristic metaphyseal widening and cupping.

6S DIFFERENTIAL DIAGNOSIS baby who is short for gestational age, any baby who has disproportionate shortening of the limbs Achondrogenesis type 1 is characterised by or trunk, and in any baby with multiple poor ossification of the skull, multiple rib congenital abnormalities. There are several dif­ fractures and very short, broad bones of the ferent conditions that may produce low birth extremities with marked bowing. In short rib weight or short length for gestation infant. These polydactyly syndrome and thanatophoric dyspla­ include placental insufficiency, foetal-maternal sia there is ossification of the vertebral column endocrine defect, chromosomal abnormalities, and pelvis. The bones of the extremities have a dysmorphology syndrome, intrauterine infection, different appearance than in achondrogenesis. skeletal dysplasia, etc (Sillence, 1978). In the Severe hypophosphatasia is differentiated by the assessment of the small infant details of the absent or severely delayed ossification of the skull pregnancy, delivery, obstetric and family history and the delicate appearance of the tubular bones and the initial examination of the neonate and its with characteristic metaphyseal ossification placenta may provide a clue to the underlying defects (Spranger, 1974). Histologically achon­ cause. An accurate assessment of gestation is drogenesis type 1 is probably a primary necessary to interpret measurements of length, disorder of connective tissue and shows severe weight and head circumference· in the newborn. retardation of chondrocytic proliferation in the The mother's menstrual history may be the only physeal cartilage. On the other hand, achondro­ reliable index of gestational age. Having establi­ genesis type 2 is probably a disoder representing shed that an infant is disproportionately short, degeneration of proliderating epiphyseal cells one must determine whether the shortening with extremely dificient matrix (Yang, 1976). primarily affects the trunk or the limbs and if the Further discussion on the differential diagonsis latter whether it is proximal (rhizomelic) middle may be found in Saldino (1971) and Xanthakos segment (mesomelic) or distal (acromelic) or a et al. (1973). combination of these.

GENETICS If skeletal dysplasia is suspected a proper Saldino, 1971 mentions of two families in work-up would include:- which multiple siblings were affected, one of these parents were consanguinous. He also 1. History: Family and maternal obstetric his- mentions a case where one of a pair of twins was tory, affected while the other was normal. This 2. Clinical examination strongly suggests that achondrogenesis, both 3. Clinical photographs, types, are genetically determined disorders with 4. X-lay examination: skeletal survey - baby­ an autosomal recessive mode of transmission. gram There is, therefore, one in four risk of recurrence S. Morphological studies of chodroosseous tissue: for each subsequent child of parents who have biopsy, autopsy. produced an affected infant. However, the 6. Other: Chromosome study, immune function, lethality of the condition should be stressed when biochemistry etc. counselling parents who are contemplatihg pro­ creation. Equally it should be emphasised that The evaluation of a baby with skeletal dys­ there is a three out of four chance that any plasia requires a multidisciplinary approach further offspring will be normal. utilising clinical, radiographic, genetic and mor­ phological findings. Although we still do not have DISCUSSION a satisfactory classification of skeletal dysplasia, the present one based on clinical and radiogra­ An underlying skeletal dysplasia should be phic features has evolved a concept that is suspected in the differential diagnosis of any invaluable for proper family counselling and for

66 till' medical care of the children affected, and 9. Chondroectoderrnal dysplasia or Ellis van enables a Iairlv prompt and accurate diagnosis in t rcvcld syndrome (Ev'C). most eas-es. This is the International Nomemcla­ 10. <. .nnpomclic dysplasia. ture Ior ConstitutionsI Diseases of which 11.·\elwl1druplasia homozygous type. \\ as adopted in 1970 and further revised in 1977. I.:!. ( h..nd rodvplaxin punta rhizornelic type. This clnssificarion (Rimion, 1978) divides the 13. type 2 (lethal prei­ skeletal dysplasias into two major groups: The natal type). chondrodvsplasius (abnormal growth and deve­ 14. Hypophosphatasia (severe). ioprnent of cartilage and/or bone) and the 15. Congenital osteopetrosis. dvsostoses (malformations of individual bones, singlY or in combination). The short-limbed ACKNOWLEDGEMENT dwarfisrns or chondrodysplasias are subdivided into those disorders that are manifest at birth This is to acknowledge our thanks to Mr. and those that become apparent later in life. Wong Meng Lye of the Department of Medical Neonatal chondrodysplasias are again subdivided Photography, General Hospital, Seremban. into those disorders that are almost always lethal (stillborn or die soon after birth) and those in which the baby usually survives the neonatal REFERENCES period. Rimoin, D. L. (1978): International nomenclature of The disorder that comprise lethal neonatal constitutional disease of bone ..J, Paediatrics, 93: 614-616. dwarfism are:- Saldino, R. M. (1971): Lethal short limbed dwarfism: achondrogenesis and thanatophoric dwarfism. Am. J. 1. Achondrogenesis type (Parenti-Housten-Har­ Roentgen. Rad. Ther. Nuc. Med., 112: 185-197. ris). Sillence, D. 0., Rimein, D. L., and Lachman, R. (1978): Neonatal dwarfism. Paediatric Clinic N. America, 25: 2. (Langer-Saldino­ 453-483. Fraccare). 3. type 1. Spranger, 1. W., Langer, L. 0., and Weidmann, H-R. 4. Thanatophoric dysplasia type 2 (clover leaf (1974): Bone dysplasias: an atlas of constitutional disorders skull) . of skeletal development. Saunders, Philadephia, pp. 24-28. Xanthakos, U. F., and Rejent, M. M. (1973): Achondrogene­ 5. Short rib polydactyly syndrome type 1 (Majew­ sis: case report and review of the literature. J. Paediatrics, ski). 82: 658-663. 6. Short rib polydactyly syndrome type 2 (Saldino Yang, 5-5., Brough, A. J., Garewal, G. S. and Bernstein, 1. -Noonan). (1974): Two types of heritable lethal achondrogenesis. J. 7. Short rib polydactyly syndrome type 3 (Nau­ Paediatrics, 85: 796-801. Yang, 5-5., Heidelberger, K. P" Brough, A. 1., Corbett, D. mom. P., and Bernstein, J. (1976): Lethal short limbed chondro­ 8. Asphyxiating thoracic dystrophy (ATDJ or dysplasia in early infancy. Perspective in Paediatric Juene syndrome. Pathology. Yearbook, Chicago, Vo!. 3, pp. 1-40.

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