638 Chromosome Trisomy 18 Syndrome 23 Chromosome Trisomy 18 Syndrome Edwards syndrome • Wide fontanels • Wormian bones Developmental and mental retardation, dolicho- • Thin calvaria cephaly, short palpebral fissures, micrognathia, over- • Hypoplasia of periorbital ridges lapping fingers, rocker-bottom feet • Hyper- or hypotelorism • Micrognathia (96%) Frequency: 1 in 5,000 births. Hands and Feet • Clenched hands, overlapping fingers Genetics • Ulnar deviation of the hand Trisomy 18; maternal age is a risk factor for aneu- • Hypoplastic thumbs, short 1st metacarpal ploidy; critical segment 18q11-q12. • Syndactyly, polydactyly, ectrodactyly • Short, hypoplastic, or absent finger phalanges Clinical Features • Equinovarus feet, rocker-bottom feet • Growth deficiency, failure to thrive • Toe syndactyly (2nd and 3rd toes most frequently • Hypoplastic skeletal muscle and subcutaneous fat involved) • Microcephaly, narrow bifrontal diameter, promi- • Hypoplastic, absent proximal hallucal phalanx nent occiput • Dysmorphic/absent toe phalanges • Short palpebral fissures, epicanthal folds, ptosis, Extremities microphthalmia, corneal opacities • Most pronounced changes involve the mesomelic • Short upper lip, small mouth, cleft lip/palate segments of the limbs • Micrognathia • Thin long bones • Low-set, dysplastic ‘fawn-like,’ posteriorly rotated • Tibial aplasia ears • Patellar aplasia • Shield-chest, short sternum, hypoplastic nipples • Genu valgum • Umbilical and inguinal hernia, diastasis recti • Radial hypoplasia • Cryptorchidism, hypoplastic labia majora, small Chest pelvis, limited hip abduction • Asymmetrical thorax, wide thorax, pectus excava- • Clenched hand, overlapping of index fingers over tum 3rd, 5th fingers over 4th, arches on fingertips, • Incomplete ossification of clavicles (middle por- hypoplastic nails tions), thin clavicles • Short, dorsiflexed hallux, prominent heel • Thin ribs, 11 pairs of ribs • Skin redundancy, hirsutism, cutis marmorata • Short sternum, reduced number of sternal ossifi- • Cardiac defects cation centers • Hypotonia, followed by hypertonia Spine • Severe mental retardation • Hemivertebrae, fused vertebrae, scoliosis Pelvis Differential Diagnosis • Small pelvis, narrow ilia, relatively large pelvic • Other chromosome imbalances inlet • Short and vertical ischia Radiographic Features • Unossified pubic rami Skull • Hip dysplasia • Dolichocephaly (93%) Generalized Bone Defects • Prominent occiput • Delayed bone age • Microcephaly (70%) • Stippled epiphyses Chromosome Trisomy 18 Syndrome 639 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) C a b abc Fig. 23.2 a–c. Three newborns. a In patient 2 note cranial dolichocephaly with prominent occiput, wide open sutures asymmetry,wide fontanels,cleft palate,micrognathia,and thin and fontanels, hypoplasia of facial bones, and micrognathia. clavicles and ribs. b In patient 3 facial asymmetry, small orbits, (Reprinted, with permission, from Dallapiccola and Pistocchi and cervical spine anomalies are seen. c In patient 1 note 1972) 640 Chromosome Trisomy 18 Syndrome 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 Fig. 23.3. Patient 4,newborn.Ribs are thin and elongated,with the axial skeleton in human trisomy 18 fetuses. Am J Med segmentation defects in upper right thorax, and fewer in num- Genet 1996; 65: 332–6 ber on left (11 pairs). Clavicles are also thin, with lateral hooks. Mastroiacovo P,Dallapiccola B,Andria G,Camera G,Lungarot- The heart silhouette is enlarged. (Reprinted, with permission, ti MS. Difetti congeniti e sindromi malformative. McGraw- from Dallapiccola and Pistocchi 1972) 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 abc Fig. 23.4. a Patient 5, newborn: note severely deformed lower note severe varus deformity of left foot, equinovarus defor- limbs, with tibial aplasia on right, and bilateral clubfoot and mity and genu valgum on right. c Patient 3, newborn: note hip dislocation. Note also small pelvis, with short, vertically cavus deformity of the foot. (Reprinted, with permission, from oriented ischia, and enlarged pelvic inlet. b Patient 6, newborn: Dallapiccola and Pistocchi 1972) Chromosome Trisomy 18 Syndrome 641 Fig. 23.5 a,b. Two newborns: a patient 1, b patient 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 C b a.