Wolf-Hirschhorn Syndrome, 4p16.3 Deletion, FISH
Aids in the diagnosis of Wolf-Hirschhorn syndrome, in conjunction with CMS / Chromosomes Analysis, for Congenital Disorders, Blood
Detecting cryptic translocations involving 4p16.3 that are not demonstrated by conventional chromosome studies
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Wolf-Hirschhorn syndrome is associated with a deletion on the short arm of chromosome 4 (4p16.3). The syndrome is manifested by pre- and postnatal growth retardation and severe hypotonia (decreased muscle tone). The common major birth defects include microcephaly (small head), cleft lip and/or palate, and severe heart malformations. Facial features include cranial asymmetry, prominent forehead, hemangioma, preauricular pits or tags, coloboma of the iris or other eye malformations, hypertelorism (wide-spaced eyes), micrognathia (small jaw), and a long neck. Many other birth defects have been seen including brain and kidney malformations, hernias, abnormal external and internal genitalia, simian crease (single palmar crease), and cutis aplasia (failure of skin development) of the scalp. Most affected individuals are stillborn or die in the first year, although survival beyond age 20 has been reported. Mental retardation is profound, and survivors have seizures and severe hypotonia.
FISH studies are highly specific and do not exclude other chromosome abnormalities. For this reason we recommend that patients suspected of having Wolf-Hirschhorn syndrome also have conventional chromosome studies (CMS / Chromosomes Analysis, for Congenital Disorders, Blood) performed to rule out other chromosome abnormalities or translocations.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Any individual with a normal signal pattern (2 signals) in each metaphase is considered negative for a deletion in the region tested by this probe.
Any patient with a FISH signal pattern indicating loss of the critical region will be reported as having a deletion of the regions tested by this probe. This is consistent with a diagnosis of Wolf-Hirschhorn syndrome (4p16.3 deletion).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because this FISH test is not approved by the FDA, it is important to confirm Wolf-Hirschhorn syndrome by other established methods such as clinical history or physical examination.
In a series of 58 patient specimens (peripheral blood, amniotic fluid, tissue, or products of conception) this FISH identified a deletion in 14 patients with a phenotype consistent with Wolf-Hirschhorn syndrome or a cytogenetic or telomere 4p deletion. Seven additional patients with chromosome abnormalities involving chromosome 4, but not containing the 4p16.3 deletion, were further characterized using this probe set. This demonstrated the probe's ability to define other chromosome 4 rearrangements in this region that are not consistent with 4p16.3 deletion. In 37 patient samples with a normal karyotype or FISH telomere analysis results, no deletions of the Wolf-Hirschhorn critical region were identified.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Van Dyke DL, Wiktor A: Chapter 26: Clinical cytogenetics. In Laboratory Medicine. Sixth edition. Edited by K McClatchey. Baltimore, Williams and Wilkins, 2002
2. Jones K: Deletion 4p syndrome. In Smith’s Recognizable Patterns of Human Malformation. Sixth edition. Philadelphia, Elsevier Saunders, 2005
3. Rodriguez L, Zollino M, Climent S, et al: The new Wolf-Hirschhorn syndrome critical (WHSCR-2): a description of a second case. Am J Med Genet 2005;136:175-178