Hypogonadotropic Hypogonadism/Kallmann Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
5243 ANOS1 81406,81479 Order Options and Pricing
AXL 81479,81479
CCDC141 81479,81479
CHD7 81407,81479
DUSP6 81479,81479
FEZF1 81479,81479
FGF17 81479,81479
FGF8 81479,81479
FGFR1 81405,81479
FLRT3 81479,81479
FSHB 81479,81479
GNRH1 81479,81479
GNRHR 81479,81479
HESX1 81479,81479
HS6ST1 81479,81479
IL17RD 81479,81479
KISS1 81479,81479
KISS1R 81479,81479
LEP 81479,81479
LEPR 81406,81479
LHX3 81479,81479
LHX4 81479,81479
NR0B1 81404,81479
NSMF 81479,81479
PCSK1 81479,81479
PROK2 81479,81479
PROKR2 81479,81479
PROP1 81404,81479
SEMA3A 81479,81479
SEMA3E 81479,81479
SOX10 81479,81479
SOX2 81479,81479
SOX3 81479,81479
SPRY4 81479,81479
SRA1 81479,81479
TAC3 81479,81479
TACR3 81479,81479
WDR11 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
5243Genes x (38)81479 81404, 81405, 81406, 81407, 81479 $930 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Hypogonadotropic hypogonadism (HH), also known as gonadotropin-releasing hormone (GnRH) deficiency (IGD), is a genetic condition that is characterized by delayed or absent sexual development and infertility due to an impaired secretion of gonadotropins. Hypogonadotropic hypogonadism is divided into two major clinical phenotypes depending on the presence of an intact sense of smell: anosmic hypogonadotropic hypogonadism (Kallmann syndrome, KS) and normosmic hypogonadotropic hypogonadism (nHH) (Marino et al. 2014. PubMed ID: 25254043; Boehm et al. 2015. PubMed ID: 26194704; Kim. 2015. PubMed ID: 26790381; Balasubramanian et al. 2017. PubMed ID: 20301509). The prevalence of HH has been estimated to range from 1:10,000 to 1:86,000 individuals depending on different populations (for example 1:10,000 in French and 1:86,000 in Sardinian). A recent study in Finland showed a minimal incidence of KS which accounts for nearly two thirds of individuals with HH of 1:30,000 in males and 1:125,000 in females (Laitinen et al. 2011. PubMed ID: 21682876). Males predominate in HH with a male-to-female ratio of nearly 4:1 (Seminara et al. 1998. PubMed ID: 9793755).

HH is typically diagnosed in patients presenting with absent or incomplete puberty, low serum testosterone or estradiol due to absence of circulating gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone), but no other abnormalities of the hypothalamic-pituitary axis (Balasubramanian et al. 2017. PubMed ID: 20301509). Infant boys with HH often demonstrate micropenis and cryptorchidism. Adult males with HH present failure to undergo normal puberty and absence of secondary sexual characteristics. Females with HH usually have little or no breast development, primary amenorrhea or infertility. In addition to reproductive symptoms, many KS patients exhibit a wide variety of additional signs and symptoms. Commonly recognized non-reproductive features that may be present in KS patients include: digital synkinesia, unilateral renal agenesis, cleft lip and /or palate, dental agenesis, hearing loss, and abnormal eye movements (Kaplan et al. 2010. PubMed ID: 20949504; Layman 2013. PubMed ID: 23650337; Balasubramanian et al. 2017. PubMed ID: 20301509).

Hormone replacement with testosterone in males and estrogen in females is the classic treatment for hypogonadism. Hypogonadotropic hypogonadism is one of the rare conditions in which specific medical treatment can reverse infertility. Early intervention can promote the development of and maintain secondary sexual characteristics and normal sexual function, prevent low bone density and related complications, and also provides the opportunity for fertility (Boehm et al. 2015. PubMed ID: 26194704).

Genetics

HH is a clinically and genetically heterogeneous disorder. To date, pathogenic variants in more than 35 genes account for about half of all HH. The most common causes of HH are pathogenic variants in the ANOS1 (KAL1), CHD7, FGFR1, GNRHR, IL17RD, PROKR2, SOX10, and TACR3 genes (Marino et al. 2014. PubMed ID: 25254043; Balasubramanian et al. 2017. PubMed ID: 20301509). These genes are known to be involved in the formation and migration of GnRH and olfactory neurons. Pathogenic variant in these genes haven been reported to disrupt the migratory pathway of GnRH and olfactory neurons from the nasal region into the hypothalamus. HH can be inherited in X-linked, autosomal dominant or recessive manner. Some of these genes have also been associated with oligogenic inheritance. See individual gene test descriptions for information on molecular biology of gene products.

Clinical Sensitivity - Sequencing with CNV PGxome

This multi-gene panel analyzes genes associated with hypogonadotropic hypogonadism/Kallmann syndrome. Clinical sensitivity for this NGS test is ~50% (Balasubramanian et al. 2017. PubMed ID: 20301509).

Gross deletions in ANOS1 (KAL1) have been reported in 5-10% of patients with X-linked recessive inheritance (Ahmadzadeh et al. 2015. PubMed ID: 26629483). Only 4 large deletions and genomic complex rearrangements involving FGFR1 were reported in patients affected with Kallmann syndrome or related disorders (Fukami et al. 2013. PubMed ID: 23657145). Gross deletions or duplications of other genes in this panel have not been reported in patients with Hypogonadotropic Hypogonadism/Kallmann syndrome (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides at least 97.7% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as >20X NGS reads or Sanger sequencing.

A list of regions not covered by NGS or Sanger sequencing is available upon request.

Genes without complete coverage: ANOS1, CCDC141, CHD7, FGF8, NSMF and SOX3.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with symptoms consistent with hypogonadotropic hypogonadism/Kallmann syndrome.

Diseases

Name Inheritance OMIM ID
CHARGE Association AD 214800
Follicle-Stimulating Hormone Deficiency, Isolated AR 229070
Hypogonadotropic Hypogonadism 10 with or without Anosmia AR 614839
Hypogonadotropic Hypogonadism 11 with or without Anosmia AR 614840
Hypogonadotropic Hypogonadism 12 with or without Anosmia AR 614841
Hypogonadotropic Hypogonadism 13 with or without Anosmia AR 614842
Hypogonadotropic Hypogonadism 14 with or without Anosmia AD 614858
Hypogonadotropic Hypogonadism 15 with or without Anosmia AD 614880
Hypogonadotropic Hypogonadism 16 with or without Anosmia AD 614897
Hypogonadotropic Hypogonadism 17 with or without Anosmia AD 615266
Hypogonadotropic Hypogonadism 18 with or without Anosmia AD 615267
Hypogonadotropic Hypogonadism 19 with or without Anosmia AD 615269
Hypogonadotropic Hypogonadism 20 with or without Anosmia AD 615270
Hypogonadotropic Hypogonadism 21 with Anosmia AD 615271
Hypogonadotropic Hypogonadism 22, with or without Anosmia AR 616030
Hypogonadotropic Hypogonadism 7 with or without Anosmia AR 146110
Hypogonadotropic Hypogonadism 8 with or without Anosmia AR 614837
Hypogonadotropic Hypogonadism 9 with or without Anosmia AD 614838
Isolated X-Linked Adrenal Hypoplasia Congenita XL 300200
Kallmann Syndrome 1 XL 308700
Kallmann Syndrome 2 AD 147950
Kallmann Syndrome 3 AD, AR 244200
Kallmann Syndrome 4 AD, AR 610628
Kallmann Syndrome 5 AD 612370
Kallmann Syndrome 6 AD 612702
Microphthalmia Syndromic 3 AD 206900
Obesity, Morbid, Due to Leptin Deficiency AR 614962
Obesity, Morbid, Due to Leptin Receptor Deficiency AR 614963
Panhypopituitarism X-Linked XL 312000
Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, And Hirschsprung Disease AD 609136
Pituitary Hormone Deficiency, Combined 2 AR 262600
Pituitary Hormone Deficiency, Combined 3 AR 221750
Pituitary Hormone Deficiency, Combined 4 AD 262700
Proprotein Convertase 1/3 Deficiency AR 600955
Septooptic Dysplasia AR,AD 182230

Related Test

Name
PGxome®

Citations

  • Ahmadzadeh et al. 2015. PubMed ID: 26629483
  • Balasubramanian et al. 2017. PubMed ID: 20301509
  • Boehm et al. 2015. PubMed ID: 26194704
  • Fukami et al. 2013. PubMed ID: 23657145
  • Human Gene Mutation Database (Bio-base).
  • Kaplan et al. 2010. PubMed ID: 20949504
  • Kim. 2015. PubMed ID: 26790381
  • Laitinen et al. 2011. PubMed ID: 21682876
  • Layman 2013. PubMed ID: 23650337
  • Marino et al. 2014. PubMed ID: 25254043
  • Seminara et al. 1998. PubMed ID: 9793755

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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