Wolf-Hirschhorn Syndrome, 4p16.3 Deletion, FISH
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/8696 Chromosomes Analysis, for Congenital Disorders, Blood) performed to rule out other chromosome abnormalities or translocations.
Aids in the diagnosis of Wolf-Hirschhorn syndrome, in conjunction with CMS/8696 Chromosomes Analysis, for Congenital Disorders, Blood
Detecting cryptic translocations involving 4p16.3 that are not demonstrated by conventional chromosome studies
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.
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.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Van Dyke DL, Wiktor A: Clinical cytogenetics. In Laboratory Medicine. 6th edition. Edited by K McClatchey. Baltimore, Williams & Wilkins, 2002, Chapter 26
2. Jones K: Deletion 4p syndrome. In Smith’s Recognizable Patterns of Human Malformation. 6th 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