Pediatr Radiol (1981) 10:155-160 Pediatric Radiology �9 Springer-Verlag 1981

New Forms of Neonatal Death Dwarfism Report of 3 Cases

K. Kozlowski, T. Tsuruta, Y. Kameda, A. Kan and G. Leslie

Departments of Radiology and Pathology, Royal Alexandra Hospital for Children, Sydney, Australia; Department of Orthopaedic Surgery, Mie University School of Medicine, Mie-Ken, Japan; The Clinical Laboratories, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; and Neonatal Intensive Care Unit, Royal North Shore Hospital, Sydney, Australia

Abstract. T h e t e r m L e t h a l N e o n a t a l D w a r f i s m

( D e a t h D w a r f i s m ) d e n o t e s b o n e d y s p l a s i a s w h i c h

a l w a y s h a v e a f a t a l o u t c o m e . T h r e e d i f f e r e n t c a s e s of

" n e w " f o r m s o f d e a t h d w a r f i s m a r e r e p o r t e d . A

b a b y g r a m s h o u l d b e a r o u t i n e e x a m i n a t i o n in al l t h e

c a s e s of s t i l l b o r n b a b i e s o r t h o s e w h o d i e s o o n a f t e r

t h e b i r t h . I f t h e n t h e d i a g n o s i s c a n n o t b e e s t a b l i s h e d

m i c r o s c o p i c i n v e s t i g a t i o n s of t h e g r o w t h c a r t i l a g e

s h o u l d b e p e r f o r m e d .

Key words: D e a t h d w a r f i s m - A c h o n d r o g e n e s i s -

T h a n a t o p h o r i c d w a r f i s m - O s t e o g e n e s i s i m p e r f e c t a

c o n g e n i t a

T h e a u t h o r s w i s h t o r e p o r t 3 d i f f e r e n t , n e w f o r m s of

l e t h a l n e o n a t a l s h o r t - l i m b e d d w a r f i s m ( l e t h a l n e w -

b o r n c h o n d r o d y s p l a s i a ) . T o t h e b e s t of o u r k n o w l -

e d g e s i m i l a r ca se s w e r e n o t ye t r e p o r t e d [ 1 - 7 ] .

Report of the Cases

Case L This stillborn, male patient born at 35 weeks gestation showed mongoloid appearance and omphalocele. Weight 1850 g. Length 32 cm. Hydramnios 3200 ml. The 29 years old para 1, gravida 1 mother, received hormonal therapy at the age of 24 because of amenorrhea from the age of 20-24. There was negative family history and the father was 32 years old (Fig. 1A and B).

The X-ray examination revealed generalised bone changes most marked in the appendicular skeleton. The humeri, femora, fibulae and metacarpals were missing. There were 5 bones in the fingers and 4 in the toes - probably corresponding to the distal phalanges. The forearm bones and the tibiae had a most peculiar triangular shape. The trunk was shortened. The spine was dysplas- tic and its development was markedly retarded. The clavicles were long and curved peripherally. In the scapulae the acetabulae were hypoplastic and the pelvis showed hypoplastic iliac bodies and absent pubic bones. There were no gross abnormalities of the skull (Fig. 1 C-G).

Microscopic examination confirmed marked retardation of endochondral ossification in the long bones with considerably reduced proliferation of cbondrocytes and narrow zone of hyper- trophy at the growth plates (Fig. H). In the misshapen triangular bones of the extremities epiphyseal plate was present at one edge only and endochondral ossification was absent at the opposite apex where unremodelled osseous trabeculae were in direct contact with fibrous tissue which took the place of a cartilage epiphyseal plate (Fig 1). Small amounts of glycogen were present in the chon- drocytes.

Case II. This male patient was born at 34 weeks gestation weighing 1860g., crown-heel length 30.5cm, upper limbs 8.0cm and occipito-frontal circumference 30.5 cm (Fig. 2A).

The 31 year old, para 0, gravida 3, mother presented at 28 weeks gestation with acute polyhydramnios. Both ultrasonic examination at 11 weeks and X-ray examination at 14 weeks showed a singel fetus with short limbs and small trunk. Because of marked maternal discomfort at 30 weeks 700 ml of amniotic fluid was removed by transabdominal amniocentesis. Labour was intro- duced at 34 weeks because of recurrent polyhydramnios resulting in delivery of an infant with markedly short limbs, small trunk and large cystic mass in the occipital region. Post mortem examination demonstrated that the occipital mass was a cystic scalp lesion and that there was a single fused adrenal gland. Karyotype was 46 XX.

The X-ray examination showed generalised changes most marked in the appendicular skeleton. No definite abnormalities were noted in the skull (Fig. 2B-D).

Case IlL This female patient was born as a full term infant after normal gestation weighing 3226 g (Fig. 3 A). After the delivery the child was resuscitated. Respiratory distress was described as due to Pierre Robin anomaly. Apgar 1'-1, 5 ' -3, 10'-7. It was noted that the child had bizzare facies, flat nose with depressed nasal bridge and short limbs with dislocated knees and ankles, flexed knees and hips and bilateral talipes equino-varus.

The 16 years old para 1, gravida 1 mother received Debendox for hyperemesis during the pregnancy. There was otherwise a negative family history.

The newborn was brought to the RAHC at the age of 4 hours, cyauosed with tachycardia and tachypnea. He died at the age of 9 hours.

The X-ray examination showed predominant changes in the appendicular skeleton. No definite abnormalities were noted in the skull (Fig. 3 B-E).

0 3 0 1 - 0 4 4 9 / 8 1 / 0 0 1 0 / 0 1 5 5 / $ 0 1 . 2 0

156 K. Kozlowski et al.: Neonatal Death Dwarfism. 3 "New" Forms

Fig. 1 A-L Case L "'New", unclassified type of neonatal death dwarfism. A and B Extreme shortening of the extremities. Note protrusion of the triangular bones of the extremities. Five fingers, but only four toes are present (halluxes are missing). Note dysmorphic features of the skull. C Anatomic specimen of the spine and ribs. Note dysmorphic vertebrae and ribs. D Retarded bone age and dysplastic changes of the spine. Shortening of the thoracic spine and crowding of the ribs. Hypoplastic pelvis and scapular acetabulae. Absent pubic bones. Well developed, long curved clavicles. E Absent femora, fibulae and pubic bones. Peculiar, triangular shape of the tibiae. F The fingers are extremely short and only single ossification centres in each finger is seen. They are localised at the periphery of the fingers and correspond in localisation to the distal phalanges

K. Kozlowski et al.: Neonatal Death Dwarfism. 3 "New" Forms 157

Fig. 1 A - I . Case L "New", unclassified type of neonatal death dwarfism. G There are only four toes bilaterally. Similarly to the fingers the toes show single ossification centres locatised at the periphery corresponding in localisation to the distal phalanges. H H & E x 20. Ulna: markedly reduced chondrocyte prolifera- tion and narrow zone of hypertrophy at the growth plate. I H & E x 20 Radius: absent epiphyesal plate at the apex of the triangle. Unremodel led osseous trabeculae are in contract with fibrous tissue. Endo-membranous ossification is minimal

158 K. Kozlowski et al.: Neonatal Death Dwarfism. 3 "New" Forms

Fig. 2A-D. Case II. "New", unclas- sified type of neonatal death dwarf- ism. A Extreme shortening of the ex- tremities. Soft tissue swelling around the neck. Note facial dysmorphism and shortening of the trunk. B-D Extreme shortening of the long tubular bone with irregularly out- lined, flared metaphyses. Meta- physes showing more rapid growth are more severly affected. Note ab- normal shape of the scapulae and ab- normal shape and irregular outlines of the iliac bones. There is deficient ossification of the spine with extreme platyspondyly of the lower thoracic and upper lumbar vertebral bodies. The ribs are shortened and flare anteriorly. Note the relatively long clavicles and grossly normal skull

On the autopsy the lungs were poorly aerated, with extensive intrapulmonary bleeding. Haemorrhages were also present in the right lateral ventricle and in the falx cerebri.

Microscopic examination revealed that enchondral ossification at the costo-chondral junctions was essentially normal but this

process appears retarded in the long hones of the extremities. The zones of chondrocyte proliferation and hypertrophy were irregu- larly thinned and in some areas the columnar alignement of chon- drocytes in these zones was disturbed. Glycogen granules were demonstrable within the chondrocytes (Fig. 3 F).

K. Kozlowski et al.: Neonatal Death Dwarfism. 3 "New" Forms 159

Fig. 3A-F. Case IlL "'New", unclassified type of neonatal death dwarfism. A Note shortening of the extremities and dysmorphic facial features. B Note dysplastic humeri with hypoplastic forearm bones and with relatively large ulnae. The pubic bones are small but otherwise the pelvis shows little abnormality. The fibulae are absent. The femora and tibiae show no gross abnormality. C and D Note defective ossification of the hand and foot. Radio-ulnar pseudoarthrosis. E Coronal vertebral clefts with posterior parts of the vertebral bodies being absent in the thoracic spine~ F H & E • 25. Lower tibial epiphysis showing uneven thickness of zone of proliferation and generally thinned zone of hypertrophy with disturbed alignment of the chondrocytes

160 K. Kozlowski et al.: Neonatal Death Dwarfism. 3 "New" Forms

Discussion

The review of the available literature and cases of neonatal death dwarfism observed by the authors did not reveal any identical disorders [1-7].

Case I shows unique radiographic appearances and is different from all the recognised forms of neonatal death dwarfism. I t shows similarity in the shape of the tibiae to Nievergeld syndrome [6] but in Nievergeld's syndrome the femora and humeri are present and if affected their shape is usually relatively little altered. Further, our Case I showed also changes in the axial skeleton and the ossification pat- tern of the hands and feet is unique.

Case I I also shows unusual X-ray abnormalities. Ext reme shortening of the long bones was accom- panied by mushroomed widening of the ends of the shafts which was never seen in that extent by the authors. There are however two diseases which bear some resemblance to our patient: 1. Achondro- genesis I and 2. Metatropic Dwarfism. Phenotypi- cally the child resembles Achondrogenesis I. How- ever, the X-ray appearances are not the same. In Achondrogenesis I the long bones have a stellatae appearance, similar to that of the iliac bones, whereas in our case the long bones of the extremities have a different shape. The scapulae are also different in shape f rom those in Achondrogenesis I. The pos- sibilitiy that our case is a more mature case of Achon- drogenesis I can not be rejected with absolute cer- tainty [3].

In the severe forms of Metatropic Dwarfism the pelvis and the short tubular bones are well ossified and the ends of the shafts are smooth [5].

Unfortunately no bone specimens were taken for histopathology examination.

Case I I I shows also some unusual features. The most striking abnormalities are absence of the distal parts of the humeri, deformity of the forearm bones

and absent fibulae. The senior author had seen two cases showing some similarities to the present one. That of Dr. Isdale from Johannesburg showed aplasia of both humeri and femora, thin but otherwise nor- mal forearm bones, absent fibulae and slightly deformed tibiae [2]. Another case of Prof. Cremin f rom Cape Town showed severe aplasia of the hu- meri, deformed forearm bones and absent fibulae. It also showed narrowing of the thoracic spinal canal and hypoplasia of the bodies of the iliac bones [1].

We are uncertain as to the primary cause of this peculiar pat tern of changes and the relationship be- tween these three cases of neonatal rhizomelic dwarf- ism with absent fibular ossification centres. An exter- nal noxious agent was considered. The histologic changes between our Case I I I and the case of Dr. Isdale [2] are different.

References

1. Cremin B (1979) Personal communication 2. Isdale J (1979) Personal communication 3. Kozlowski, K, Masel J, Morris L, Ryan J, Collins E, Van Vliet

P, Woolnough H (1977) Neonatal death dwarfism (Report of 17 cases). Australas Radiol 21:164

4. Kozlowski K, Masel J, Morris L, Kunze D (1978) Neonatal death dwarfism (A further report). R6fo 129:626

5. Kozlowski K, Morris L, Reinwein H, Sprague P, Tamaela LA (1976) Metatropic dwarfism and its variants (Report of six cases). Australas Radiol 20:367

6. Maroteaux P (1974) Maladies osseuses de l'enfant. Edition Flammarion, Paris

7. Ryan J, Kozlowski K (1971) Radiography of stillborn infants. Australas Radiol 15:213

Date of final acceptance: October 23, 1980

Dr. K. Kozlowski Royal Alexandra Hospital for Children Camperdown 2050, N.S.W. Australia