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Postnatal chromosomal analysis

Indication:

  • Dysmorphic features.
  • Failure to thrive.
  • Developmental delay and/or mental retardation.
  • Infertility and multiple pregnancy loss.
  • Family history of chromosome abnormality.
  • Ultrasound abnormalities or family history of chromosome abnormality.
  • Congenital anomalies
  • Ambiguous genitalia
  • Hypogonadism / undescended testes / hypospadias
  • Delayed menarche and short stature

Method:

Culture of peripheral lymphocytes (72 hrs), G-banded chromosome analysis
Specimen Requirements:
3-5 ml blood in sodium heparin vaccutainer (green top tube) transported at room temperature
Turnaround time:  3-4 weeks

Chromosome breakage analysis

Chromosome breakage analysis is performed when there is a clinical suspicion of Fanconi anemia (Fanconi pancytopenia). Cultured lymphocytes are treated with the DNA cross-linking agent. Affected individuals exhibit very high levels of chromosome breakage with this treatment while unaffected individuals have little or no increase at all.

 

Indication:

  • Anemia
  • Bone marrow failure
  • Birth defects
  • Developmental or eating problems.

 

Method:

Culture of peripheral lymphocytes with mitogen (Mitomycin C) for 72 h
Specimen Requirements:
Blood (7 ml in sodium heparin) from patient and age/sex matched control.

Turnaround time:  3-4 weeks


Chromosomal analysis for fragile x syndrome

Indication:

  • Any male or female with mental retardation (borderline to severe), developmental delay or learning disabilities of unknown cause.
  • Any male or female with autism or autistic-like characteristics.
  • Any male or female with a relative who has fragile X syndrome or mental retardation of unknown cause.

Anyone with a previous positive or equivocal result by the fragile X cytogenetic test, confirmation of the presence of the FMR1 mutation is important.

Method:

Culture of peripheral lymphocytes with thymidine for 72 h.

Specimen Requirements:

3-5 ml blood in sodium heparin vaccutainer (green top tube) transported at room temperature
Turnaround time:  3-4 weeks


Fluorescence in situ hybridization (FISH) for microdeletion syndrome

  • 1p36.3 Microdeletion Syndrome
  • DiGeorge Syndrome, Microdeletion 22q11.2
  • Williams’s syndrome
  • Sex Determining Region(SRY)
  • Cri-du-chat syndrome
  • Prader-Willi syndrome (PWS)
  • Angelman syndrome
  • Smith-Magenis syndrome
  • Miller-Dieker syndrome
  • Kallmann Syndrome, Xp22.3 Deletion.
  • Steroid sulfatase deficiency syndrome
  • SOTOS syndrome




  • 1p36.3 Microdeletion Syndrome

Chromosome 1p microdeletion syndrome is associated with a spectrum of dysmorphic features and mental retardation. The syndrome can be suspected in overweight patients with mental retardation, heart defects, and finger abnormalities. Facial features include microcephaly (small head), short neck, malformed ears, and small deep-set eyes. The phenotype is variable and depends on the size of the deletion.

  • DiGeorge Syndrome, Microdeletion 22q11.2

DiGeorge syndrome is a disorder caused by the deletion of a small piece of chromosome22. The deletion occurs near the middle of the chromosome at a location designated q11.2. The features of this syndrome vary widely. Symptoms may include heart defects, cleft palate, recurrent infections, kidney abnormalities, low levels of calcium in the blood, thrombocytopenia, feeding difficulty, hearing loss, developmental delays, and learning disabilities.

  • Williams syndrome

A developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate intellectual disability, unique personality characteristics, distinctive facial features, heart and blood vessel (cardiovascular) problems.  Williams’s syndrome is caused by missing genes from a specific region of chromosome 7. The deleted region includes more than 25 genes and researchers believe that a loss of several of these genes probably contributes to the characteristic features of this disorder. Although Williams syndrome is considered an autosomal dominant condition, most cases are not inherited, but occur as random events during the formation of reproductive cells (eggs or sperm) in a parent of an affected individual.

  • Sex Determining Region(sry)

The SRY (sex-determining region on the Y chromosome) gene is required for normal embryonic wolffian (male) genital development, although numerous other genes are involved in completing the process of normal male development. Some gene mutations block the action of SRY in development. Thus, a 46, XY individual with an SRY deletion or mutation will develop as a female, and a 46, XX individual with translocation of SRY to 1 X chromosome will develop as a male. Structural abnormalities of the Y chromosome result in a spectrum of abnormalities from primary infertility (male or female) to various forms of ambiguous genitalia. SRY-negative 46, XX males often have ambiguous genitalia, whereas those who are positive for SRY usually have a normal male phenotype with azoospermia. SRY-negative 46, XY females may have another mutation, such as 1 involving the SOX9 gene.


  • Cri-du-chat syndrome

Cri du chat syndrome, also known as 5p- (5p minus) syndrome or cat cry syndrome, is a genetic condition that is caused by the deletion of genetic material on the small arm (the p arm) of chromosome 5. Infants with this condition often have a high-pitched cry that sounds like that of a cat. The disorder is characterized by intellectual disability and delayed development, small head size, low birth weight, weak muscle tone in infancy, and distinctive facial features. While cri du chat syndrome is a genetic condition, most cases are not inherited.

  • Prader-Willi syndrome (PWS)

Prader-Willi syndrome (PWS) is a complex genetic condition that affects many parts of the body. At birth, babies with PWS have poor muscle tone and a weak cry. Initially, they are slow feeders and appear undernourished. The feeding problems improve after infancy and often between 2 to 4 years of age; children with PWS become much focused on food and have difficulty controlling their appetite. The overeating often results in rapid weight gain and obesity. Individuals with PWS also often have developmental delays and less-than-average adult height. PSW is caused by missing or non-working genes on chromosome 15. Most cases are not inherited, but occur randomly.

  • Angelman syndrome

Angelman syndrome is a genetic disorder that primarily affects the nervous system. Characteristic features of this condition include developmental delay, intellectual disability, severe speech impairment, problems with movement and balance (ataxia), epilepsy, and a small head size. Individuals with Angelman syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. Many of the characteristic features of Angelman syndrome result from the loss of function of a gene called UBE3A. Most cases of Angelman syndrome are not inherited, although in rare cases a genetic change responsible for Angelman syndrome can be inherited from a parent.

  • Smith-Magenis syndrome

Smith-Magenis syndrome is a developmental disorder that affects many parts of the body. The major features of this condition include mild to moderate intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems. Most people with Smith-Magenis syndrome have a deletion of genetic material from a specific region of chromosome 17. Although this region contains multiple genes, researchers believe that the loss of one particular gene, RAI1, in each cell is responsible for most of the characteristic features of the condition. Smith-Magenis syndrome is not typically inherited, but results from a genetic change that occurs during the formation of reproductive cells (eggs or sperm) or in early fetal development.

  • Miller-Dieker syndrome

Miller-Dieker syndrome is a genetic condition characterized by lissencephaly, typical facial features, and severe neurologic abnormalities. Symptoms may include severe intellectual disability, developmental delay, seizures, muscle stiffness, weak muscle tone and feeding difficulties. Miller-Dieker syndrome is caused by a deletion of genetic material near the end of the short (p) arm of chromosome 17. Treatment is symptomatic and supportive.

  • Kallmann Syndrome, Xp22.3 Deletion.

Kallmann syndrome is associated with a deletion on the short arm of the X chromosome. The syndrome is an X-linked disease and can be suspected in patients with complete absence of smell (anosmia), hypogonadism, and delayed sexual development. The phenotype may include gynecomastia, bimanual synkinesis (1 hand copying the movements of the other hand), shortened 4th metacarpal bone, and absence of a kidney. Kallmann syndrome affects mainly males, but rare cases of affected females have been reported.

  • Steroid sulfatase deficiency syndrome

Steroid sulfatase deficiency syndrome is associated with a deletion of the STS gene on the short arm of X chromosome (Xp22.3). The syndrome is an X-linked form of ichthyosis, which is a group of cutaneous disorders characterized by increased or abnormal keratinization. The phenotype is variable, with affected males presenting with dry and scaly skin, sparse hair, and conical teeth.

  • SOTOS syndrome

Sotos syndrome, also known as cerebral gigantism, is a childhood overgrowth syndrome characterized by distinctive facial features including prominent forehead, downward slanting palpebral fissures, and pointed chin, macrocephaly and learning disability.  The physical characteristics are often accompanied by delayed social, cognitive, language, and motor development.  Behavioral disturbances including anxiety, withdrawal, depression, phobias, sleep disturbance, tantrums, aggressiveness, inappropriate speech, and irritability are seen in approximately 60-80% of children diagnosed with Sotos syndrome.  

Method:

Metaphase fluorescence in situ hybridization  
Specimen Requirements:
5-3 ml blood in sodium heparin vaccutainer (green top tube) transported at room temperature
Fixed cell pellet
Turnaround time:  10-15days