Pediatr Ra diol (1993) 23:442-445
Short stature, mental retardation, craniosynostosis, Klippel-Feil syndrome, Scheuerman kyphosis, rib gaps and other distinctive skeletal and genital anomalies
A new syndrome?
K. Kozlowski ~, D. Sillence 2, F. Taylor 3
1 Department of Radiology, Royal Alexandra Hospital for Children, Sydney, Australia 2 Department of Genetics, Royal Alexandra Hospital for Children, Sydney, Australia 3 Department of Orthopaedic Surgery, Royal Alexandra Hospital for Children, Sydney Australia
Received: 23 February 1993/Accepted: 22 March 1993
Pediatric Radiology 9 Springer-Verlag 1993
Abstract. A 12-year-old girl with a syndrome of short stat- ure, mental retardat ion and mult iple, distinctive skeletal anomal ies such as craniosynostosis, hamate-capi tate fu- sion, first r ib gaps, Kl ippel-Fei l anomaly and Scheuerman- l ike kyphosis is reported.
on the right thumb and arches on the right index and right fifth fin- gers. She also had an enlarged clitoris and underdeveloped scro- talized labia. In view of the ambiguous genitalia a vaginogram was performed and this showed almost complete duplication of the inter- nal genitalia with a double uterus. A severe irreducible kyphosis was present in the upper thoracic spine.
A large number of syndromes with short stature, menta l retardat ion and mult ip le skeletal anomal ies have been re- ported. The finding of craniosynostosis, hamate-cap i tate fusion, first rib gaps and progressive Scheuerman- l ike kyphosis in a 12-year-old occasioned review of her new- born and chi ldhood features. These point to a unique short stature, mental retardat ion, mult iple skeletal anom- alies syndrome.
This child was ascertained at birth as having multiple dysmorphic features. Birth weight at term was 2832 g (10th-25th percentile), head circumference 33.5 cm (10th-50th percentile). The forehead was high and prominent. There was a large posterior fontanelle with a small anteriorly placed anterior fontanelle, The hairline was low posteriorly and the neck short, Ears were low set and shortened in their longitudinal axis with a broad thickened tragus and hypoplastic lobules. Palpebral fissures were short with an anti-mongoloid slant. The palate was high-arched and narrow anteriorly. Both thumbs were proximally placed and showed fixed flexion. Elbow extension was limited. There was bilateral fifth finger clinodactyly and bilat- eral transverse palmar creases. Chromosomal studies were normal. Parents were unrelated with two previous children who are both well. A thoracic kyphosis was recognized at 12 months of age.
When seen at 12 years of age the girl was cheerful and co-opera- five with mental retardation. She was of short stature with a height of 126.5 cm (3rd percentile), span 116 cm, upper segment/lower seg- ment ratio of 61.5/65 = 0.93 (Fig. 1). There was microbrachycephaly with a low posterior hairline. She had bilateral ptosis with hyperte- lorism, outer canthus 90 mm (75th percentile). The nose was broad and fleshy. Both hands showed many fine small transverse and ob- lique lines on the palmar surface. The dermal prints showed whorls
Correspondence to: Dr. K. Kozlowski, Royal Alexandra Hospital for Children, Camperdown 2050, NSW, Australia
Fig. 1. The patient aged 12 years. Note the bushy hair, thick brows and wide depressed nasal bridge
Fig. 2 a-d. Radiographs of the new- born patient showing increased bone density. a Large anterior fontanelle. Steep, small anterior cranial fossa. Promi- nent forehead. b Mild hypotubulation of the long bones and minor hypoplasia of the first metacarpal, and middle and dis- tal phalanges. e Small distal femoral epiphyses. Absent tibial epiphyses. d Bell-shaped chest. Thin, shortened ribs
were within normal limits. In the hands the tufts of the distal phalanges were absent and the distal phalanges of the first and second fingers were hypoplastic, as were the middle phalanges of the second and fifth fingers and the first metacarpal. There was coalition of the hamate and capitate, with the remaining metacarpals being small and abnormally shaped. In the feet the changes were less obvious. Pointed distal phalanges and bifid epiphyses of the great toe may be present as normal variants. However, a rhomboid shape of the great toe, quarter-moon-shaped epiphyses of the pointed distal phalanx and small oval-shaped middle phalanges are not encountered in the normal population. Cuneiform I was broader and positioned more anteriorly than usual (Fig. 3).
Radiographic fin dings
The skeletal survey performed in the newborn period showed loss of cortico-medullary demarcation in tubular bones with apparently in- creased density consistent with benign osteosclerosis. The skull showed a round-shaped cranium with prominent forehead, oblit- erated anterior fontanelle and coronal suture and a very large poste- rior fontanelle. The anterior cranial fossa was small and there were prominent digital markings in the occipital and parietal bones. There was also some hypoplasia of the facial bones. The upper extremities showed proximal shortening of the radius, and hypoplasia of the thumb and of the middle and distal phalanges. The chest was triangu- lar in shape with obliquely positioned, slightly shortened ribs (Fig.2).
The skeletal survey performed at the age of 12 years showed some unique features. There was a "beaten copper" microcephalic skull with fusion of the cranial sutures. In the chest the ribs were ob- lique in position and the first ribs showed gaps. The long bones of the upper extremities were slightly bowed with mild proximal shor- tening of the radius. In the pelvis, the iliac bones were small and there was spina bifida of the sacrum. In the spine there was fusion of C2 and C3. There was irregularity of the vertebral plates and wedging of the lower thoracic and upper lumbar vertebrae. The middle and upper thoracic vertebrae and lower lumbar vertebrae
This patient has a syndrome which includes craniosyn- ostosis and multiple skeletal malformations. Her featu- res overlap with known craniosynostosis , known microcephalic osteodysplastic dwarfism [2, 3] and known short stature syndromes [2, 3], but the spectrum and natural history of the anomalies suggest a unique short stature/mental retardation/multiple skeletal anom- alies syndrome.
Of the acrocephalopolydactyly and acrocephalosyn- dactyly syndromes, Carpenter syndrome [1-3] could be considered, but the absence of polydactyly and the me- tacarpo-phalangeal anomalies, pelvic changes and ky- phosis in this patient are not found in Carpenter syn- drome. First rib gaps have been reported in partial or mo- saic trisomy 8  and cerebro-costo-mandibular syn- drome . However, no other radiographic changes characteristic of tr isomy 8 mosaicism such as hypoplastic patellae, retarded bone age or radial head dislocation were present in our patient. Craniosynostosis and carpal fusion are not features of trisomy 8. Multiple rib in- volvement is characteristic of cerebro-costo-mandibular syndrome .
The bony changes superficially resemble hand-foot- uterus syndrome , which shows short thumbs, pointed distal phalanges without normal tuft and shortening of the middle phalanx of the fifth finger. However, the first meta- carpal in hand-foot-uterus syndrome is short but of nor- mal diameter and a prominent pseudoepiphysis is usually
Fig.3a-f. Radiographs of thepatient aged 12 years. a Microcephaly and craniosynostosis with "beaten copper" appearance. Obliteration of intervertebral disc space and fusion of C2 and C3. b Hypoplasia of the tubular bones of the thumb, of the sec- ond finger and middle phalanx of the fifth finger. Fusion of the capitate and hamate. The remaining carpal bones are slightly hypoplastic/dysplastic. c Pelvis showing coxa valga with hypoplastic ischial and pubic bones and a wide symphysis pubis. d Thin, obliquely positioned ribs with gaps in the first ribs (arrows). e Bowed radius and humerus. Distal shortening of the ulna. f Large, slightly dysplastic tubular bones of the great toe with pointed distal phalanx and quarter-moon-shaped epiphyses. The middle phalanges are unusual in size and shape, being short and oval
present at the distal end. The wrist changes in hand-foot- uterus syndrome are characterized by trapezium-sca- phoid fusion and accessory os centrale is frequently pre- sent. In the feet the cuneiforms are fused to either the navicular or the metatarsals.
Fusion of C2 and C3 is consistent with the diagnosis of Klippel-Feil syndrome. The latter is often associated with a host of other, variable musculo-skeletal, genito-urinary, neurological and cardio-respiratory anomalies or may be a feature of a well-differentiated syndrome: Mayer-Roki- tansky-Kuster-Hauser, Duane syndrome and fetal alcohol
syndrome [2, 3, 7, 8]. The unique constellation of skeletal and genital anomalies with mental retardation as present in our patient has, to the best of our knowledge, never been reported with Klippel-Feil syndrome.
The inheritance of this present syndrome is uncertain. Chromosomal studies were normal. Either a fresh muta- tion or autosomal recessive inheritance must be con- sidered.
1. Gorlin RJ, Cohen MM, Levin LS (1990) Syndromes of the head and neck. Oxford University Press, Oxford
2. Buyse ML (1990) Birth defects encyclopedia. Blackwell Scientific, Oxford
3. Taybi H, Lachman RS (1990) Radiology of syndromes, me- tabolic disorders and skeletal dysplasia. Year Book, Chicago London
4. Kozlowski K, Collis J, Suter M, Sillence D (1988) The rib gap anomaly in partial or mosaic trisomy 8. Skeletal Radiol 17: 251- 254