Cerebral Palsy due to Chromosomal Anomalies and Continuous Gene Syndromes
Section snippets
Diagnosis during the neonatal period
Chromosomal disorders and contiguous gene syndromes should be considered in any neonate that presents with any of the following conditions:
The syndrome of muscular hypotonia with brisk deep tendon reflexes (atonic cerebral palsy) in the absence of a history of perinatal asphyxia or trauma.
Whenever neonatal hypotonia is accompanied by two or more major congenital anomalies, particularly when these involve the mesodermal or endodermal germ layers.
In the presence of minor congenital anomalies,
Down syndrome (trisomy 21)
Down syndrome (trisomy 21) is the most common autosomal anomaly in live births. The most recent figures in the United States (1997) indicate a prevalence of 9.9 per 10,000 live births, and 43% occur in births to women aged 35 years and older [10]. This is significantly less than the prevalence of 1 in 500 that was recorded in 1950, and reflects the effectiveness of prenatal screening programs [11].
Down syndrome is associated with an extra chromosome 21 or an effective trisomy for chromosome 21
Structural autosomal anomalies
Several cytogenetically visible structural anomalies of the autosomal chromosomes have been reported and have been accompanied by neurologic defects, notably mental retardation and microcephaly. The most common of these entities is a deletion of the short arm of chromosome 5 (5p−), which causes the cri du chat syndrome, and the deletion of the short arm of chromosome 4 (4p−; Wolf-Hirschhorn) syndromes.
Subtelomeric abnormalities
Deletions, duplications, and cryptic imbalance rearrangements of the telomeres—the terminal segments of chromosomes—have received an increasing amount of attention in the past few years. It has become apparent that abnormalities in these regions are responsible for at least 5% to 10% of nonsyndromic mental retardation, as well as for cases of mental retardation that are associated with multiple congenital anomalies. Several techniques have been used to screen for these abnormalities. FISH is
Sex chromosome abnormalities
Sex chromosome abnormalities consist of various aneuploidies that involve the sex chromosomes. As determined by most surveys of the newborn population or of cells that are obtained at amniocentesis [38], the prevalence of sex chromosome abnormalities is approximately 2.5 in 1000 phenotypic male subjects and 1.4 in 1000 phenotypic female subjects (see Table 2). Although considerable geographic variation occurs, the two most common abnormalities in phenotypic male subjects are the XYY and the XXY
Chromosomal anomalies in various dysmorphic syndromes (contiguous gene syndromes, microdeletion syndromes)
In addition to deletions that are detected readily cytogenetically, combined molecular and cytogenetic analysis has led to the identification of small deletions in several clinically well-defined syndromes (see Table 1). The term “contiguous gene syndrome,” which was coined by Schmickel [50], refers to the patterns of phenotypic expression that result from the inactivation or overexpression as a result of deletion, duplication, or other means, of a set of adjacent genes in a specific chromosome
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