Cerebral Palsy due to Chromosomal Anomalies and Continuous Gene Syndromes

https://doi.org/10.1016/j.clp.2006.03.001Get rights and content

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

First page preview

First page preview
Click to open first page preview

References (85)

  • T. Strachan et al.

    Human molecular genetics

    (2004)
  • P.A. Jacobs et al.

    Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding

    J Med Genet

    (1992)
  • E.B. Hook et al.

    How much difference does chromosome banding make?

    Ann Hum Genet

    (1989)
  • N.P. Kuleshov

    Chromosome anomalies of infants dying during the perinatal period and premature newborn

    Hum Genet

    (1976)
  • M. Shevell et al.

    Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

    Neurology

    (2003)
  • M. Ferguson-Smith et al.

    Cytogenetic analysis

  • B. Carvalho et al.

    High resolution microarray comparative genomic hybridization analysis using spotted oligonucleotides

    J Clin Pathol

    (2004)
  • C. Bendavid et al.

    Multicolor FISH and quantitative PCR can detect submicroscopic deletions in holoprosencephaly patients with a normal karyotype

    J Med Genet

    (2006)
  • C.L. Olsen et al.

    Down syndrome: interaction between culture, demography, and biology in determining the prevalence of a genetic trait

    Hum Biol

    (2003)
  • J.A. Böök et al.

    Empiric risk figures in mongolism

    JAMA

    (1950)
  • T. Hassold et al.

    Down syndrome: genetic recombination and the origin of the extra chromosome 21

    Clin Genet

    (2000)
  • D.R. Rowe et al.

    Cardiac malformation in mongolism. A prospective study of 184 mongoloid children

    Am J Med

    (1961)
  • M. Suetsugu et al.

    Spine distribution along the apical dendrites of the pyramidal neurons in Down's syndrome

    Acta Neuropathol

    (1980)
  • K.E. Wisniewski et al.

    Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome

    Ann Neurol

    (1985)
  • R.E. Mrak et al.

    Trisomy 21 and the brain

    J Neuropathol Exp Neurol

    (2004)
  • A. Levinson et al.

    Variability of mongolism

    Pediatrics

    (1955)
  • K. Fishler et al.

    Mental development in Down syndrome mosaiciscm

    Am J Ment Retard

    (1991)
  • S.M. Pueschel et al.

    Atlantoaxial instability in individuals with Down syndrome: epidemiologic, radiographic, and clinical studies

    Pediatrics

    (1987)
  • E.J. Glasson et al.

    The changing profile of people with Down's syndrome: implication for genetic counselling

    Clin Genet

    (2002)
  • S.M. Day et al.

    Mortality and causes of death in persons with Down syndrome in California

    Dev Med Child Neurol

    (2005)
  • M.S. Christensen et al.

    Treatment-related death in childhood acute lymphoblastic leukaemia in the Nordic countries: 1992–2001

    Br J Haematol

    (2005)
  • J. Nielsen et al.

    Incidence of chromosome abnormalities in newborn children. Comparison between incidences in 1969–1974 and 1980–1982 in the same area

    Hum Genet

    (1982)
  • M.B. Forrester et al.

    Trisomies 13 and 18: prenatal diagnosis and epidemiologic studies in Hawaii, 1986–1997

    Genet Test

    (1999)
  • A.D. Carothers et al.

    Trends in prenatal diagnosis of Down syndrome and othrautosomal trisomies in Scotland 1990 to 1994, with associated cytogenetic and epidemiological findings

    Genet Epidemiol

    (1999)
  • J.L. Ramirez-Castro et al.

    Anatomical analysis of the developmental effects of aneuploidy in man – the 18-trisomy syndrome: II. Anomalies of the upper and lower limbs

    Am J Med Genet

    (1978)
  • B.J. Baty et al.

    Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk

    Am J Med Genet

    (1994)
  • J.A. Golden et al.

    Central nervous system malformations in trisomy 9

    J Neuropath Exp Neurol

    (1993)
  • A. Schinzel

    Catalogue of unbalanced chromosome aberrations in man

    (2001)
  • T.J. Wright et al.

    Wolf-Hirschhorn and Pitt-Rogers-Danks syndromes caused by overlapping 4p deletions

    Am J Med Genet

    (1998)
  • M. Sase et al.

    Ultrasonographic findings of facial dysmorphism in Wolf-Hirschhorn syndrome

    Am J Perinatol

    (2005)
  • D.A. Koolen et al.

    Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation

    Eur J Hum Genet

    (2005)
  • M.A. Ferguson-Smith et al.

    Maternal age specific rates for chromosome aberration and factors influencing them: report of a collaborative study on 52,965 amniocenteses

    Prenat Diagn

    (1984)
  • Cited by (19)

    • Cerebral palsy and related neuromotor disorders: Overview of genetic and genomic studies

      2022, Molecular Genetics and Metabolism
      Citation Excerpt :

      However, most disease-causing genomic alterations are too small to be visualized under the light microscope and require molecular techniques such as chromosomal microarray analysis or genome sequencing for detection. Anecdotal reports of patients with CP and various chromosomal abnormalities have occasionally appeared in the medical literature [43–46], and a few patients with segmental gain or loss of genomic material large enough to be seen cytogenetically and a “cerebral palsy” phenotype are reported in the DECIPHER or ClinVar databases (Table 2). However, we are not aware of any study describing the results of routine cytogenetic testing in a large series of patients with CP.

    • Genetics and genomics of cerebral palsy

      2023, Neurodevelopmental Pediatrics: Genetic and Environmental Influences
    • Movement Disorders in Childhood, Third Edition

      2022, Movement Disorders in Childhood, Third Edition
    • Prenatal and perinatal causes, risk factors, diagnosis and prevention of neonatal cerebral palsy

      2021, Review of Clinical Pharmacology and Pharmacokinetics, International Edition
    View all citing articles on Scopus
    View full text