Aliases: KS, Kallmann syndrome, Type I; X-linked Kallmann syndrome; Kallmann syndrome, X-linked; Dysplasia olfactogenitalis of De Morsier;
Gene(s) involved: KAL1 on chromosome Xp22.31
Brief description of disorder: Kallmann syndrome (KS) is characterized by idiopathic or isolated hypogonadotropic hypogonadism (IHH) and an impaired or absent sense of smell. Affected males usually present with cryptorchidism and micropenis in infancy. Adults and adolescents typically exhibit incomplete sexual maturity and hypogonadism. Adult males lack secondary sexual characteristics, exhibit a diminished libido, and may exhibit erectile disfunction and infertility. Associated findings include agenesis of teeth, corpus callosum, and kidney unilaterally (30%), as well as brachydactyly, syndactyly, synkinesia of digits (80%).
The prevalence of KS (Types 1-4) is roughly 1 in 10,000 - 86,000.
Inheritance pattern: KS is inherited in an X-linked fashion. Approximately 70% of affected males are simplex cases.
Genetics: For all types of KS, only about 25% have defined gene mutations. The other 75% of cases are undefined and unmapped genetic anomalies. KAL1 mutations, such as point, missense, splice-site, and nonsense mutations are detectable via sequence analysis in approximately 5-10% of affected males. Whole gene deletions are not typically seen and are therefore rarely detectable by FISH or array. Terminal deletions on Xq22.3 result in a contiguous gene syndrome characterized by Kallmann syndrome with the addition of mental retardation, short stature, chondrodysplasia punctata, and steroid sulfatase deficiency. These terminal deletions are detectable by FISH. However FISH testing is frequently utilized to confirm karyotype findings and to better define the positional rearrangements.
Test method: Conventional cytogenetic analysis, FISH and array. Gene mutation testing is not available at this facility for this disorder.
Test sensitivity: Cytogenetic analysis detects approximately 25% of deletions that are greater than 5 Mb. FISH and array will detect 98-100% of deletions/duplications that are greater than 100 kb; however, deletions/ duplications smaller than 100kb will not be detected on array and deletions/duplications smaller than the FISH probe will not be detected.
Specimen requirements for Cytogenetic Analysis, FISH, and Array:
Adult: 3-5 ml peripheral blood in a sodium-heparin tube.
Newborn: 1-3 ml blood in a sodium-heparin tube.
Turn-around-time
Newborns: 2-3 days
Non-STAT: 2-14 days
FISH: 6-8 days
Array CGH: 7-14 days
References: GeneReviews
Revised 5-24-2011
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