Kallmann Syndrome, Xp22.3 Deletion, FISH
Aids in the diagnosis of Kallmann syndrome, in conjunction with conventional chromosome studies (CMS / Chromosome Analysis, for Congenital Disorders, Blood)
Detecting cryptic translocations involving Xp22.3 that are not demonstrated by conventional chromosome studies
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 fourth metacarpal bone, and absence of a kidney. Kallmann syndrome affects mainly males, but rare cases of affected females have been reported.
FISH studies are highly specific and do not exclude other chromosome abnormalities. For this reason, we recommend that patients suspected of having Kallmann syndrome also have conventional chromosome studies (CMS / Chromosome 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 females and 1 signal in males) 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 on an X chromosome will be reported as having a deletion of the regions tested by this probe. This is consistent with a diagnosis of Kallmann syndrome (Xp22.3 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 Kallmann syndrome diagnoses by other established methods, such as clinical history or physical examination.
FISH analysis was performed on a series of 32 patient peripheral blood specimens and compared to cytogenetic or FISH telomere analyses and the patient's phenotype. Using a probe for the Kallmann syndrome, FISH analysis identified a deletion in 1 patient with an X chromosome deletion identified by karyotype analysis and in 1 patient a rearrangement of the X chromosome was further characterized using this probe set. No deletions of the Kallmann critical region were identified in 28 specimens from phenotypically normal males and females. Two patients with a normal result by the KAL1 probe were found to have Xp telomere deletions.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Meitinger T, Heye B, Petit C, et al: Definitive localization of X-linked Kallmann syndrome (hypogonadotropic hypogonadism and anosmia) to Xp22.3: close linkage to the hypervariable repeat sequence CRI-S232. Am J Hum Genet 1990 Oct;47(4):664-669
2. Weissortel R, Strom TM, Dorr HG, et al: Analysis of an interstitial deletion in a patient with Kallmann syndrome, X-linked ichthyosis and mental retardation. Clin Genet 1998 Jul;54(1):45-51