23 Chromosome Trisomy 18 Syndrome
Edwards syndrome
Developmental and mental retardation, dolicho- cephaly, short palpebral fissures, micrognathia, over- lapping fingers, rocker-bottom feet
Frequency: 1 in 5,000 births.
Genetics
Trisomy 18; maternal age is a risk factor for aneu- ploidy; critical segment 18q11-q12.
Clinical Features
• Growth deficiency, failure to thrive
• Hypoplastic skeletal muscle and subcutaneous fat
• Microcephaly, narrow bifrontal diameter, promi- nent occiput
• Short palpebral fissures, epicanthal folds, ptosis, microphthalmia, corneal opacities
• Short upper lip, small mouth, cleft lip/palate
• Micrognathia
• Low-set, dysplastic ‘fawn-like,’ posteriorly rotated ears
• Shield-chest, short sternum, hypoplastic nipples
• Umbilical and inguinal hernia, diastasis recti
• Cryptorchidism, hypoplastic labia majora, small pelvis, limited hip abduction
• Clenched hand, overlapping of index fingers over 3rd, 5th fingers over 4th, arches on fingertips, hypoplastic nails
• Short, dorsiflexed hallux, prominent heel
• Skin redundancy, hirsutism, cutis marmorata
• Cardiac defects
• Hypotonia, followed by hypertonia
• Severe mental retardation Differential Diagnosis
• Other chromosome imbalances
Radiographic Features Skull
• Dolichocephaly (93%)
• Prominent occiput
• Microcephaly (70%)
• Wide fontanels
• Wormian bones
• Thin calvaria
• Hypoplasia of periorbital ridges
• Hyper- or hypotelorism
• Micrognathia (96%) Hands and Feet
• Clenched hands, overlapping fingers
• Ulnar deviation of the hand
• Hypoplastic thumbs, short 1st metacarpal
• Syndactyly, polydactyly, ectrodactyly
• Short, hypoplastic, or absent finger phalanges
• Equinovarus feet, rocker-bottom feet
• Toe syndactyly (2nd and 3rd toes most frequently involved)
• Hypoplastic, absent proximal hallucal phalanx
• Dysmorphic/absent toe phalanges Extremities
• Most pronounced changes involve the mesomelic segments of the limbs
• Thin long bones
• Tibial aplasia
• Patellar aplasia
• Genu valgum
• Radial hypoplasia Chest
• Asymmetrical thorax, wide thorax, pectus excava- tum
• Incomplete ossification of clavicles (middle por- tions), thin clavicles
• Thin ribs, 11 pairs of ribs
• Short sternum, reduced number of sternal ossifi- cation centers
Spine
• Hemivertebrae, fused vertebrae, scoliosis Pelvis
• Small pelvis, narrow ilia, relatively large pelvic inlet
• Short and vertical ischia
• Unossified pubic rami
• Hip dysplasia
Generalized Bone Defects
• Delayed bone age
• Stippled epiphyses
Chromosome Trisomy 18 Syndrome 638
Chromosome Trisomy 18 Syndrome 639
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Fig. 23.1 a, b. Patient 1, newborn.
Growth deficiency, hypoplastic subcutaneous fat, microcephaly, short palpebral fissures, microg- nathia, low-set, dysplastic, posteri- orly rotated ears, small pelvis, clenched hands with distinctive overlapping fingers, and lower limb deformities. (Reprinted, with permission, from Mastroiacovo et al. 1990)
a
b
Fig. 23.2 a–c. Three newborns. a In patient 2 note cranial asymmetry, wide fontanels, cleft palate, micrognathia, and thin clavicles and ribs. b In patient 3 facial asymmetry, small orbits, and cervical spine anomalies are seen. c In patient 1 note
dolichocephaly with prominent occiput, wide open sutures and fontanels, hypoplasia of facial bones, and micrognathia.
(Reprinted, with permission, from Dallapiccola and Pistocchi 1972)
a b c
Bibliography
Baty BJ, Blackburn BL, Carey JC. Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk. Am J Med Genet 1994; 49: 175–88
Dallapiccola B, Pistocchi GF. Skeletal malformations caused by chromosome aberrations. Clinical and radiological study.
Minerva Med 1972; 63: 5049-208
De Grouchy J, Turleau C: Clinical atlas of human chromo- somes. Wiley, New York, 1977
Embleton ND, Wyllie JP, Wright MJ, Burn J, Hunter S. Natural history of trisomy 18. Arch Dis Child Fetal Neonatal Ed 1996; 75: 38–41
Hodes ME, Cole J, Palmer CG, Reed T. Clinical experience with trisomies 18 and 13. J Med Genet 1978; 15: 48–60
Kjaer I, Keeling JW, Hansen BF. Pattern of malformations in the axial skeleton in human trisomy 18 fetuses. Am J Med Genet 1996; 65: 332–6
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Taylor AI. Autosomal trisomy syndromes: a detailed study of 27 cases of Edwards’ syndrome and 27 cases of Patau’s syn- drome. J Med Genet 1968; 5: 227–52
Chromosome Trisomy 18 Syndrome 640
Fig. 23.3. Patient 4, newborn. Ribs are thin and elongated, with segmentation defects in upper right thorax, and fewer in num- ber on left (11 pairs). Clavicles are also thin, with lateral hooks.
The heart silhouette is enlarged. (Reprinted, with permission, from Dallapiccola and Pistocchi 1972)
Fig. 23.4. aPatient 5, newborn: note severely deformed lower limbs, with tibial aplasia on right, and bilateral clubfoot and hip dislocation. Note also small pelvis, with short, vertically oriented ischia, and enlarged pelvic inlet. b Patient 6, newborn:
note severe varus deformity of left foot, equinovarus defor- mity and genu valgum on right. c Patient 3, newborn: note cavus deformity of the foot. (Reprinted, with permission, from Dallapiccola and Pistocchi 1972)
a b c
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Fig. 23.5 a, b. Two newborns: a patient 1, bpatient 3. Typical changes in the upper limb include cubitus valgus, ulnar devia- tion of the hand, V-shaped position of fingers 2 and 3, camptodactyly, clinodacty- ly, and absent or hypoplastic middle pha- langes
a
b
