Frequency: 1 in 700–800 live births; much higher related to conceptions, but spontaneous abortion fol- lows in more than 60% of cases and stillbirth in about 20%; the incidence increases with increasing maternal age (incidence at the 16th week of pregnan- cy is 1 in 300 for 35-year-old expectant mothers, rising to 1 in 22 in 45-year-olds).
Genetics
In 95% of cases regular trisomy 21 is present, which arises in more than 90% of patients from maternal nondysjunction, usually at the 1st meiotic division (80%); at least 1% of patients have mosaicism with normal and trisomy 21 cell lines arising from either mitotic nondysjunction in a trisomy 21 zygote (80%) or in a normal zygote; in 4% of cases the extra copy of chromosome 21 is translocated (either one parent is a carrier of a balanced translocation or the translo- cation is due to a de novo mutation); the critical Down syndrome region responsible for the pheno- type is 22q22.3, and contiguous genes are implicated (OMIM 190685).
Clinical Features
• Delayed motor milestones, mental retardation, hypotonia, Alzheimer disease
• Short stature
• Brachycephaly
• Flat face, upward slanted palpebral fissures, epi- canthus, Brushfield spots on iris
• Macroglossia, protruding tongue, fissured tongue
• Small, low-set ears, folded helix, small ear lobe
• Redundant skin about the neck
• Short, broad hands, clinodactyly of 5th fingers, palmar simian creases
• Gap between 1st and 2nd toes
• Characteristic gait
• Congenital heart defects (atrioventricular canal)
• Duodenal stenosis/atresia, Hirschsprung disease
• Increased risk of leukemia
Fig. 24.1. aPatient 1, newborn: flat face, upward slanted palpe- bral fissures, depressed nasal bridge, short neck. b Patient 2, adult: elongated face, upward slanted fissures, strabismus
a
b
Differential Diagnosis
• Other autosomal imbalances
Radiographic Features Skull
• Brachycephalic microcephaly
• Flat occiput, small posterior fossa
• Thin calvarium with wide sutures and delayed closure of fontanels
• Hypoplasia of the facial bones and sinuses
• Orbital hypotelorism
• Sphenoid hypoplasia
• High orbital roofs
• Short hard palate
C
Fig. 24.2. a, c Patient 3, age 5 months. The skull is brachy- cephalic, with short base and small posterior fossa. The calvar- ium is thin, with widely opened sutures and fontanels.
(Reprinted, with permission, from Dallapiccola and Pistocchi
1972) b, d Patient 4, age 4 years and 6 months. Note relative hypoplasia of the facial bones and absent pneumatization of the frontal sinuses. Note also high orbital roofs, and sclerotic mastoids
a
b
d c
Spine
• Odontoid hypoplasia, atlanto-axial instability and dislocation (symptomatic in 2–3%, radiologically evident in 18%)
• Scoliosis
• Subluxation of cervical vertebrae
• Vertebral fusions
• Flattening of cervical vertebrae
• Arthritic changes of cervical vertebrae
• Increased height and decreased AP diameter of lumbar vertebrae (newborn)
Chest
• Bell-shaped chest
• Eleven pairs of ribs
• Increased number of ossification centers of the manubrium
Pelvis
• Flared iliac wings with small acetabular angles and iliac index
• Hip dysplasia and/or dislocation
• Distal tapering of the ischium Hands and Feet
• Short hands with stubby digits
• Clinodactyly of 5th fingers (short and wide middle phalanx)
• Brachymesophalangy
• Stippled epiphyses
• Pseudoepiphyses in the hands
• Pes planus
• Metatarsus varus Extremities
• Genu valgum
• Slipped capital femoral epiphysis
• Patellofemoral instability Joints
• Joint laxity
Fig. 24.3. aPatient 5, age 2 days. b Patient 6, age 3 days. Ra- diograms taken in flexion and extension, showing odontoid hypoplasia and atlanto-axial instability
a
b
Fig. 24.4. Patient 7, age 3 months. There are 11 pairs of ribs on each side. The thorax is bell shaped
Bibliography
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Cremers MJ, Ramos L, Bol E, van Gijn J. Radiological assess- ment of the atlantoaxial distance in Down’s syndrome.Arch Dis Child 1993; 69: 347–50
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Garcia-Heras J, Rao PN. A brief review of cryptic duplications of 21q as an emerging cause of Down syndrome: practical considerations for accurate detection. Clin Genet 1999; 55:
207–11
Hernandez D, Fisher EM. Down syndrome genetics: unravel- ling a multifactorial disorder. Hum Mol Genet 1996; 5:
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Keeling JW, Hansen BF, Kjaer I. Pattern of malformations in the axial skeleton in human trisomy 21 fetuses. Am J Med Genet 1997; 68: 466–71
Johnson RC, Abalson RB. Intellectual, behavioral, and physical characteristics associated with trisomy, translocation and mosaic types of Down’s syndrome. Am J Ment Defic 1969;
73: 852–5
Lane D, Stradford B (eds). Current approaches to Down’s syn- drome. Holt, Rinehart & Winston, Austin, 1985
Pueschel SM, Scola FH, Tupper TB, Pezzullo JC. Skeletal anom- alies of the upper cervical spine in children with Down syn- drome. J Pediatr Orthop 1990; 10: 607–11
Smith GF, Berg JM. Down’s anomaly. Churchill Livingstone, London, 1976
Stempfle N, Huten Y, Fredouille C, Brisse H, Nessmann C.
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682–8
C
Fig. 24.5. a Patient 8, premature infant. Note characteristic flaring of iliac wings, with small acetabular angle and iliac index, and distally tapering ischia. b Patient 9, premature in-
fant. c Patient 3, age 5 months. d Patient 10, adult. (Reprinted, with permission, from Dallapiccola and Pistocchi 1972)
a b
d c
a b
c
C
Fig. 24.7. aPatient 3, age 5 months.
bPatient 12, age 6 years. c Patient 13, age 13 years. Note short toes, hypoplasia of the middle pha- langes, most pronounced in 5th toes, and 5th toe clinodactyly
a
b
c
