Microdeletion Syndrome Detection

Fluorescence in situ Hybridization (FISH)

Microdeletion syndromes affect every pediatric and genetics practice. The incidence of these syndromes ranges from 1 in 50,000 to 1 in 8000. Diagnosis can be complicated by a negative family history and seemingly normal routine chromosome analysis. LabCorp continues its leadership in the field of diagnostic genetics by making available high-resolution chromosome analysis and FISH for many microdeletion syndromes. A partial listing of available tests follows.

 

SyndromeLocusClinical FeaturesProbe% Detectable*
*Deletion detected in those cases that have met strict diagnostic criteria.
**FISH performed as a follow-up to a positive RT-PCR test to determine mode of inheritance (test 511210).
Angelman syndrome1,215q11.2Ataxic gait, inappropriate laughter, mental retardationD15S10

80%

(uniparental disomy in <5%)

Cri-du-chat syndrome35p15.2Characteristic cry, microcephaly, mental retardationD5S23NA
DiGeorge syndrome2,4,522q11.2Dysmorphic features, hypoplasia/aplasia of thymus and parathyroidHIRA (TUPLE1)>90%
Isolated lissencephaly617p13.3LissencephalyLIS1~40%
Kallmann syndrome2,7Xp22.3Hypogonadism, anosmia/hyposmia, obesity, mental retardation, short stature, renal abnormalities, cryptorchidism, ataxia/synkinesisKALNA
Miller-Dieker syndrome217p13.3Mental retardation, dysmorphic features, seizuresLIS1≥90%
Prader-Willi syndrome**215q11.2Infant hypotonia, mental retardation, hypogonadism, obesitySNRPN / DI5S10

70%

(uniparental disomy in 25%)

1pter deletion syndrome81p36Dysmorphic features, hypotonia, psychomotor retardation, poor/absent speechLSI p58≥95%
PTEN Hamartoma tumor syndrome910q23Includes Bannayan-Riley syndrome, Cowden syndrome, Proteus and Proteus-like syndromesPTEN11% for Bannayan-Riley syndrome
Short stature (short stature and Léri-Weill dyschondrosteosis)10,11

Xp22.3

(SHOX)

Short stature, microcephaly, hearing loss, cataracts, nasal hypoplasia, depressed nasal bridge, hypogonadism, skeletal anomalies, developmental delaySHOX2%-7%
Smith-Magenis syndrome2,1217p11.2Mental retardation, self-destructive behavior, craniofacial changes, sleep disturbancesFLI1>99%
Soto syndrome13-16

5q35

(NSDI)

Cardinal (>90%): Characteristic facial features, learning disabilities, overgrowth. Major (15% to 89%): Behavioral problems, advanced bone age, cardiac abnormal, cranial MRI abnormal, renal, scoliosis, seizuresNSDI50% of individuals of Japanese heritage and 10% of individuals of non-Japanese heritage have a 5q35 microdeletion that encompasses NSDI
Steroid sulfatase deficiency and X-linked ichthyosis2Xp22.3Absence of STS activity; ichthyosis of extensor and flexor extremities, face, and neck; possible cryptorchidism; corneal opacities, testicular cancerSTS85%
Velocardiofacial syndrome522q11.2Cleft palate, cardiac defect, developmental delayHIRA (TUPLE1)85%
Williams syndrome17,187q11.23Dysmorphic features, cardiac defect, mental retardation, outgoing personalityELN / LIMK≥95%
Wolf-Hirschhorn syndrome194p16.3Mental retardation, characteristic facies, psychomotor retardationD4S96NA

References

  1. Buxton J, Chan C, Gilbert H, et al. Angelman syndrome associated with a maternal 15q11-13 deletion of less than 200 kb. Hum Mol Genet. 1994; 3(8):1409-1413. PubMed 7987324
  2. Ledbetter D, Ballabio A. Molecular cytogenetics of contiguous gene syndromes: Mechanisms and consequences of gene dosage imbalance. In Scriver C, Beaudet A, Sly W, et al, eds.The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995:811-839.
  3. Overhauser J, Huang X, Gersh M, et al. Molecular and phenotypic mapping of the short arm of chromosome 5: Sublocalization of the critical region for the cri-du-chat syndrome. Hum Mol Genet.1994; 3(2):247-252. PubMed 8004090
  4. Driscoll D, Budarf M, Emanuel B, et al. A genetic etiology for DiGeorge syndrome: Consistent deletions and microdeletions of 22q11. Am J Hum Genet. 1992; 50(5):924-933. PubMed 1349199
  5. Goldmuntz E, Emanuel B. Genetic disorders of cardiac morphogenesis. The DiGeorge and velocardiofacial syndromes. Circ Res. 1997; 80(4):437-443. PubMed 9118473
  6. Pilz D, Macha M, Precht K, et al. Fluorescence in situ hybridization analysis with LIS1 specific probes reveals a high deletion mutation rate in isolated lissencephaly sequence. Genet Med. 1998; 1(1):29-33. PubMed 11261426
  7. Rugarli E, Ballabio A. Kallmann syndrome. From genetics to neurobiology. JAMA. 1993; 270(22):2713-2715. PubMed 8133589
  8. Battaglia A, Shaffer LG. 1p36 deletion syndrome. GeneTests., www.genetests.org. Accessed November 15, 2011.
  9. Eng C. PTEN hamartoma tumor syndrome (PHTS). GeneTests., www.genetests.org. Accessed November 15, 2011.
  10. Rappold GA, Fukami M, Niesler B, et al. Deletions of the Homeobox gene SHOX (short stature Homeobox) are an important cause of growth failure in children with short stature. J Clin Endocrinol Metab. 2002; 87(3):1402-1406. PubMed 11889216
  11. Morizio E, Stuppia L, Gatta V, et al. Deletion of the SHOX gene in patients with short stature of unknown cause. Am J Med Genet A. 2003; 119A(3):293-296. PubMed 12784295
  12. Moncla A, Piras L, Arbex OF, et al. Physical mapping of microdeletions of the chromosome 17 short arm associated with Smith-Magenis syndrome. Hum Genet. 1993; 90(6):657-660. PubMed 8444473
  13. Allanson JE, Cole TR. Sotos syndrome: Evolution of facial phenotype subjective and objective assessment. Am J Med Genet. 1996; 65(1):13-20. PubMed 8914735
  14. Tatton-Brown K, Rahman N. Clinical features of NSD1-positive Sotos syndrome. Clin Dysmorphol.2004; 13(4):199-204. PubMed 15365454
  15. Kurotaki N, Harada N, Shimokawa O, et al. Fifty microdeletions among 112 cases of Sotos syndrome: Low copy repeats possibly mediate the common deletion. Hum Mutat. 2003; 22(5):378-387. PubMed 14517949
  16. Tatton-Brown K, Douglas J, Coleman K, et al. Genotype-Phenotype associations in Sotos syndrome: An analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet. 2005; 77(2):193-204.
  17. Ewart A, Morris C, Atkinson D, et al. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet. 1993; 5(1):11-16. PubMed 7693128
  18. Osborne L. Williams-Beuren syndrome: Unraveling the mysteries of a microdeletion disorder. Mol Genet Metab. 1999; 67(1):1-10. PubMed 10329018
  19. Altherr M, Wright T, Denison K, et al. Delimiting the Wolf-Hirschhorn syndrome critical region to 750 kilobase pairs. Am J Med Genet. 1997; 71(1):47-53. PubMed 9215768

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