The Invitae Isolated Gonadotropin-releasing Hormone Deficiency (IGD) Panel analyzes three genes that are associated with IGD and Kallmann syndrome, including ANOS1 (“KAL1”). These genes were selected based on the available evidence to date. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.
ANOS1 CHD7 FGFR1
ANOS1 CHD7 FGFR1
Isolated gonadotropin-releasing hormone deficiency (IGD) manifests as hypogonadism and low concentrations of gonadotropins (luteinizing and follicle-stimulating hormones). Approximately 60% of individuals with IGD have an impaired sense of smell—a presentation that is categorized as Kallmann syndrome. The remaining 40% have a normal (normosmic) sense of smell. Adults with IGD present with incomplete sexual maturation: males have decreased muscle mass, absence of secondary sexual characteristics, erectile dysfunction, and infertility whereas females exhibit primary amenorrhea and reduced or absent breast development. Low testosterone or estradiol in conjunction with low levels of LH/FSH confirms hypogonadotropic hypogonadism in affected individuals. Hypoplasia of the olfactory bulbs or tracts is common in Kallmann syndrome. Affected individuals are typically treated with hormone replacement therapies.
Approximately 20%–30% of isolated gonadotropin-releasing hormone deficiency is explained by ANOS1 (“KAL1”), CHD7, and FGFR1.
ANOS1-related (or “KAL1-related”) IGD is X-linked recessive. FGFR1- and CHD7-related IGD are autosomal dominant.
IGD has incomplete penetrance and variable expression. ANOS1-related (or “KAL1-related”) phenotypes are typically fully penetrant.
The prevalence is estimated at 1 in 8000 males and 1 in 40,000 females.
Testing should be considered for patients who have incomplete sexual maturation and are suspected to have hypogonadotropic hypogonadism.
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Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.
Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|