Chapter 2: Clinical Correlates

Teratoma

A tumor that often contains a variety of tissues, such as bone, hair, muscle, and gut epithelium.

Pluripotent stem cell

A cell capable of differentiating into any of the three germ layers or their derivatives.

Teratoma origin

Teratomas are thought to arise from pluripotent stem cells; some may originate from primordial germ cells that stray from their normal migratory pathways or from epiblast cells.

Oropharyngeal teratoma

A teratoma that may arise from primordial germ cells or epiblast cells.

Three germ layers in teratomas

Teratomas may contain derivatives of ectoderm, mesoderm, and endoderm.

Teratoma tissue derivatives

May include gut, bone, skin, teeth, and other tissues.

Chromosomal abnormality

An abnormality involving chromosome number or chromosome structure.

Numerical chromosomal abnormality

Abnormality involving an incorrect number of chromosomes.

Structural chromosomal abnormality

Abnormality involving alteration of the structure of one or more chromosomes.

Euploid

A chromosome number that is an exact multiple of the haploid number.

Aneuploid

A chromosome number that is not an exact multiple of the haploid number.

Trisomy

Presence of an extra chromosome.

Monosomy

Loss of one chromosome.

Nondisjunction

Failure of homologous chromosomes or sister chromatids to separate during cell division.

24-chromosome gamete

Gamete produced by nondisjunction that contains 24 chromosomes instead of the normal 23.

22-chromosome gamete

Gamete produced by nondisjunction that contains 22 chromosomes instead of the normal 23.

47-chromosome conceptus

Results when a normal 23-chromosome gamete fuses with a 24-chromosome gamete, producing trisomy.

45-chromosome conceptus

Results when a normal 23-chromosome gamete fuses with a 22-chromosome gamete, producing monosomy.

Maternal age and chromosomal abnormalities

The incidence of chromosomal abnormalities, including nondisjunction, increases with maternal age, particularly at 35 years and older.

Spontaneous abortion

Pregnancy loss occurring without medical or surgical intervention.

Chromosomal abnormalities in abortuses

Approximately 50% of spontaneous abortuses have major chromosomal abnormalities.

Major chromosomal defect in conceptuses

Approximately 25% of conceptuses have a major chromosomal defect.

Most common chromosomal abnormalities in abortuses

45,X (Turner syndrome), triploidy, and trisomy 16.

Chromosomal abnormalities and major birth defects

Chromosomal abnormalities account for approximately 10% of major birth defects.

Gene mutations and major birth defects

Gene mutations account for approximately 8% of major birth defects.

Down syndrome

Chromosomal disorder most commonly caused by trisomy 21.

Trisomy 21

Presence of an extra copy of chromosome 21.

Maternal nondisjunction in Down syndrome

Approximately 75% of the nondisjunction events causing Down syndrome occur during oocyte formation.

Down syndrome and maternal age

Risk increases with maternal age, particularly after age 35.

Down syndrome and translocation

Approximately 4% of Down syndrome cases result from an unbalanced translocation involving chromosome 21.

Down syndrome and mosaicism

Approximately 1% of cases result from mosaicism following loss of an extra chromosome during mitosis.

Mosaic Down syndrome

Presence of both normal cells and cells with trisomy 21.

Down syndrome intellectual disability

Individuals with Down syndrome usually have some degree of intellectual disability.

Down syndrome cardiac defects

Cardiac defects are common.

Down syndrome craniofacial features

Features include a flat broad face, oblique palpebral fissures, and protruding tongue.

Simian crease

A single transverse crease of the palm, described as a characteristic feature in Down syndrome.

Down syndrome and Alzheimer disease

Individuals with Down syndrome have an increased frequency and earlier onset of Alzheimer disease.

Trisomy 18

Chromosomal disorder characterized by an extra chromosome 18.

Trisomy 18 features

Intellectual disability, congenital heart defects, low-set ears, flexion of fingers and hands, micrognathia, renal anomalies, syndactyly, and skeletal malformations.

Micrognathia

Abnormally small mandible.

Syndactyly

Fusion or joining of two or more digits.

Trisomy 18 prognosis

Most affected conceptuses are lost before birth, and most infants born alive die by 2 months of age.

Trisomy 13

Chromosomal disorder caused by an extra chromosome 13.

Trisomy 13 features

Intellectual disability, holoprosencephaly, congenital heart defects, deafness, cleft lip and palate, and eye defects.

Holoprosencephaly

Failure of the forebrain to divide properly.

Microphthalmia

Abnormally small eyes.

Anophthalmia

Absence of one or both eyes.

Coloboma

Defect involving the eye caused by incomplete development of an ocular structure.

Trisomy 13 prognosis

More than 90% of affected infants die during the first month after birth, and approximately 5% survive beyond 1 year.

Klinefelter syndrome

Sex chromosome abnormality occurring in males with an XXY chromosome complement.

Klinefelter karyotype

47,XXY.

Klinefelter syndrome—clinical features

Sterility, testicular atrophy, hyalinization of seminiferous tubules, and usually gynecomastia.

Klinefelter syndrome and Barr body

A Barr body is present in approximately 80% of cases.

Barr body

Condensed, inactivated X chromosome.

Klinefelter syndrome cause

Most commonly caused by nondisjunction of the XX homologues.

48,XXXY

A rarer sex chromosome complement that can occur in Klinefelter syndrome.

Klinefelter syndrome and cognitive impairment

Intellectual disability is not generally part of the syndrome, but additional X chromosomes increase the likelihood of cognitive impairment.

Klinefelter syndrome incidence

Approximately 1 in 500 males.

Turner syndrome

Sex chromosome abnormality characterized by a 45,X karyotype.

Turner karyotype

45,X.

Turner syndrome and monosomy

Turner syndrome is the only monosomy compatible with life.

Turner syndrome gonadal dysgenesis

Absence or underdevelopment of the ovaries.

Turner syndrome features

Female appearance, short stature, webbed neck, lymphedema, skeletal deformities, broad chest, and widely spaced nipples.

Turner syndrome and spontaneous abortion

Approximately 98% of fetuses with Turner syndrome are spontaneously aborted.

Turner syndrome and nondisjunction

Approximately 55% of affected females are monosomic for the X chromosome because of nondisjunction.

Turner syndrome mosaicism

Some cases result from mitotic nondisjunction producing mosaicism.

Chromatin-body negative

Absence of a Barr body in cells containing only one X chromosome.

Triple X syndrome

Sex chromosome abnormality characterized by a 47,XXX chromosome complement.

Triple X karyotype

47,XXX.

Triple X clinical presentation

Often goes undiagnosed because physical features may be mild.

Triple X-associated problems

Speech problems and self-esteem problems.

Triple X and sex chromatin bodies

Cells contain two sex chromatin bodies.

Structural chromosome abnormality

Abnormality involving one or more chromosomes that usually results from chromosome breakage.

Chromosome breakage

Breaking of chromosome material that can result in loss, rearrangement, or attachment of chromosome segments.

Partial chromosome deletion

Loss of part of a chromosome.

Cri-du-chat syndrome

Syndrome caused by partial deletion of the short arm of chromosome 5.

Cri-du-chat syndrome features

Cat-like cry, microcephaly, intellectual disability, and congenital heart disease.

Microdeletion

Deletion involving only a few contiguous genes.

Microdeletion syndrome

Syndrome resulting from a microdeletion.

Contiguous gene syndrome

Syndrome resulting from deletion involving several neighboring genes.

Contiguous gene complex

Chromosomal region containing genes affected by a microdeletion.

FISH and microdeletions

Fluorescence in situ hybridization can be used to identify sites of microdeletions.

Chromosome 15q11-q13 microdeletion

Microdeletion region associated with Angelman syndrome or Prader-Willi syndrome depending on whether the affected chromosome is maternal or paternal.

Angelman syndrome

Disorder resulting from a microdeletion on the maternal chromosome 15.

Angelman syndrome features

Intellectual disability, inability to speak, poor motor development, and unprovoked prolonged periods of laughter.

Prader-Willi syndrome

Disorder resulting from a microdeletion on the paternal chromosome 15.

Prader-Willi syndrome features

Hypotonia, obesity, intellectual disability, hypogonadism, and undescended testes.

Genomic imprinting

Differential expression of genetic material depending on whether it is inherited from the mother or father.

Maternal deletion

Chromosome 15 microdeletion inherited from the mother resulting in Angelman syndrome.

Paternal deletion

Chromosome 15 microdeletion inherited from the father resulting in Prader-Willi syndrome.

Maternal 15q11-q13 deletion

Angelman syndrome

Paternal 15q11-q13 deletion

Prader-Willi syndrome

Miller-Dieker syndrome

Contiguous gene syndrome caused by a deletion at 17p13.

Miller-Dieker syndrome features

Lissencephaly, developmental delay, seizures, and cardiac and facial abnormalities.

22q11 syndrome

Contiguous gene syndrome resulting from a deletion in chromosome region 22q11.

22q11 syndrome features

Palatal defects, conotruncal heart defects, speech delay, learning disorders, and schizophrenia-like disorder.

Fragile site

Region of a chromosome with a tendency to separate or break under certain cell culture conditions.

Folate-deficient medium

Culture condition that can reveal certain fragile chromosome sites.

CGG repeat

Repeated DNA sequence associated with fragile sites; the relevant fragile X mutation involves CGG repeats in the FMR1 gene.

FMR1 gene

Gene on the long arm of the X chromosome associated with fragile X syndrome.