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Combined Pituitary Hormone Deficiency-4 (CPHD-4) via the LHX4 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
LHX4 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8729LHX481479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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


Genetic Counselors


  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Short stature is a multifactorial developmental disorder. Combined pituitary hormone deficiency (OMIM 262700) is a genetic disorder due to at least one pituitary hormone deficiency combined with growth hormone deficiency (Machinis et al. Am J Hum Genet 69:961-968, 2001). Patients diagnosed with combined pituitary hormone deficiency usually have short stature along with growth hormone deficiency associated with thyroid-stimulating hormone (TSH), adrenocorticotropin hormone (ACTH), prolactin (PRL), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) deficiencies. Brain MRI often shows anterior pituitary hypoplasia, ectopic posterior lobe, and a poorly developed sella turcica (Machinis et al. 2001, Pfaeffle et al. J Clin Endocr Metab 93:1062-1071, 2008; Castinetti et al. J Clin Endocr Metab 93:2790-2799, 2008). In addition, Chiari malformation and corpus callosum hypoplasia have been reported in less than 8% of the patients (Machinis et al. 2001; Tajima et al. Endocr J 54:637-641, 2007; Castinetti et al. 2008).


Combined pituitary hormone deficiency is inherited as an autosomal dominant disorder (Machinis et al. 2001; Machinis et al. J Clin Endocr Metab 90:5456-5462, 2005). Variants in the LHX4 gene cause combined pituitary hormone deficiency (Machinis et al. 2001). The LHX4 gene encodes a transcription factor known as LIM-homeodomain protein 4 (LHX4), which is predicted to have a role in the genesis and development of the Rathke’s pouch (Machinis et al. 2005). LHX4 proteins contain two LIM domains and one homeobox domain. It has been reported that LHX4 is involved in the activation of the POU1F1 transcription factor, the main regulator of growth hormone secretion (Machinis et al. 2005). A mix of missense, splicing, frameshift, and gross deletion variants within the LHX4 gene have been reported (Machinis et al. 2001; Tajima et al. 2007; Pfaeffle et al. 2008; Castinetti et al. 2008; Tajima et al. Exp Clin Endocrinol Diabetes 118:405-409, 2010; Dateki et al. J Clin Endocr Metab 95:4043-4047, 2010).

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test is currently unknown.

Testing Strategy

This test provides full coverage of all coding exons of the LHX4 gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with symptoms consistent with combined pituitary hormone deficiency and family members of patients who have known LHX4 variants.


Official Gene Symbol OMIM ID
LHX4 602146
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Pituitary Hormone Deficiency, Combined 4 AD 262700

Related Tests

Combined Pituitary Hormone Deficiency (CPHD) Panel
Hypogonadotropic Hypogonadism/Kallmann Syndrome Panel


  • Castinetti, F., et.al. (2008). "A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism." J Clin Endocrinol Metab 93(7): 2790-9. PubMed ID: 18445675
  • Dateki, S., et.al. (2010). "Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion." J Clin Endocrinol Metab 95(8): 4043-7. PubMed ID: 20534763
  • Machinis, K., Amselem, S. (2005). "Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation identified in patients with pituitary defects." J Clin Endocrinol Metab 90(9): 5456-62. PubMed ID: 15998782
  • Machinis, K., et.al. (2001). "Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4." Am J Hum Genet 69(5): 961-8. PubMed ID: 11567216
  • Pfaeffle, R. W., et.al. (2008). "Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies." J Clin Endocrinol Metab 93(3): 1062-71. PubMed ID: 18073311
  • Tajima, T., et.al. (2007). "A novel missense mutation (P366T) of the LHX4 gene causes severe combined pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe and a poorly developed sella turcica." Endocr J 54(4): 637-41. PubMed ID: 17527005
  • Tajima, T., et.al. (2010). "A novel mutation (V101A) of the LHX4 gene in a Japanese patient with combined pituitary hormone deficiency." Exp Clin Endocrinol Diabetes 118(7): 405-9. PubMed ID: 19856252


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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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