Down Syndrome
Siegfried M. Pueschel
I. Description of the problem. The child with Down syndrome has recognizable physical characteristics and limited intellectual functioning due to the presence of an extra chromosome 21 or part of the long arm of chromosome 21.
A. Epidemiology.
Estimated incidence of Down syndrome is between 1 in 800-1200 live births.
3000-5000 children with Down syndrome are born each year in the United States.
There has been a slight decrease in the birth prevalence due to the increased utilization of prenatal screening (alpha fetoprotein, unconjugated estriol, free beta human chorionic gonadotropin, pregnancy-associated plasma protein-A (PAPP-A), inhibin-A, and ultrasonography) and diagnostic techniques (chorionic villus sampling, amniocentesis, and other procedures), leading to subsequent termination of the pregnancy.
There is a higher prevalence in the population because of an increased life expectancy.
B. Genetics. There are four main types of chromosome abnormalities in Down syndrome.
1. Trisomy 21 is observed in the vast majority (93%-95%) of children with Down syndrome.
2. Translocation occurs in 4%-6% of children with Down syndrome. Most translocations involve the attachment of the long arms of the supernumerary chromosome 21 to chromosome 14, 21, or 22. If a translocation is identified in a child with Down syndrome, the parents’ chromosomes need to be examined, since in about one-third of the cases a parent may be a balanced carrier of the translocation. Genetic counseling is recommended.
3. Mosaicism occurs in approximately 1%-2% of children with Down syndrome.
4. A rare chromosome aberration, partial trisomy 21, is noted in some persons with Down syndrome.
5. Much progress has been made in molecular genetics. Recent genome studies revealed that there are more than 420 genes encoded on chromosome 21 of which 145 have been studied well.
C. Etiology. Many etiologies of Down syndrome have been posited including radiation, viral infections, genetic predisposition, autoimmune processes, and others. It is well known that advanced maternal age is a definite risk factor that may be associated with problems in production line, persistent nucleoli, hormonal imbalance, delayed fertilization, and relaxed selection. Most of these theories are tentative. Recent investigations suggest that the absence or reduced proximal recombination appears to predispose to nondisjunction in meiosis I and the presence or increase of proximal exchanges predisposes to nondisjunction in meiosis II. In addition, some studies indicate an increased incidence of Down syndrome in diabetic mothers and in females with only one ovary.
II. Making the diagnosis.
A. Signs and symptoms. There is a wide variability in the characteristics of children with Down syndrome. Some individuals have only a few signs, whereas others show most of the features as listed in Table 39-1.
B. Differential diagnosis. The main features of Down syndrome are often recognized by the clinician in the neonatal period. However, on rare occasions children with other chromosomal aberrations may display a similar phenotype (e.g., newborns with 49, XXXXX syndrome may have similar facial features). Conformation by chromosome analysis is mandatory.
C. Medical concerns. Some of the medical concerns of newborn children with Down syndrome may be life-threatening and require immediate correction, whereas others may only become apparent during subsequent days and weeks or in later life.
1. Neonatal medical problems.
a. Congenital heart disease is diagnosed in 40%-50% of children with Down syndrome (most often atrioventricular canal, followed by ventricular septal defect, Tetralogy of Fallot, patent ductus arteriosus, and atrial septal defect). All newborns
with Down syndrome should be examined by a pediatric cardiologist and undergo echocardiography. A child with congenital heart disease who is in heart failure will require appropriate medical treatment. Many of these children will undergo heart surgery during the first year of life.
Table 39-1. Percentage of phenotypic findings in a group of 114 infants with Down syndrome (abbreviated list)
Sagittal suture separated
98
Oblique palpebral fissures
98
Wide space between first and second toes
96
False fontanel (widening of sagittal suture at the parietal area)
95
Plantar crease between first and second toes
94
Increased neck tissue
87
Abnormally shaped palate
85
Hypoplastic nose
83
Brushfield spots
75
Mouth kept open
65
Protruding tongue
58
Epicanthal folds
57
Single palmar crease
53
Brachyclinodactyly
51
Short stubby hands
38
Flattened occiput
35
Abnormal structure of ears
28
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