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NovaGrowth 

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Idiopathic short-stature testing 

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Genomic testing for unexplained short stature

 

A physician-ordered,

phenotype-informed pathway

NOVA TESTING PATHWAY

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INITIAL TEST

WES​

Broad assessment of coding regions with phenotype-driven interpretation.

$399

WES

$70

kit + round-trip shipping

≤6 weeks

after an acceptable sample

unresolved 

PHYSICIAN-SELECTED ESCALATION

WGS​

Broader genomic assessment when clinically appropriate.

CLINICAL CONTEXT

“Idiopathic” means unexplained, genetics may hold the answer.

Short stature may reflect normal familial variation or constitutional delay, but it can also result from endocrine disease, chronic illness, growth-plate disorders, chromosomal conditions, imprinting disorders, or monogenic syndromes. 

A molecular diagnosis is more likely when short stature is disproportionate, syndromic, associated with skeletal dysplasia, neurodevelopmental or congenital findings, persistent after small-for-gestational-age birth, or supported by a family history.

Diagnostic yield rises sharply when short stature is accompanied by syndromic, skeletal features, or parents with short stature.

Idiopathic Short Stature

 

Current evidence indicates that genetic testing identifies a monogenic cause in fewer than 15% of children with isolated short stature, compared with up to 80% of children with syndromic short stature or suspected skeletal dysplasia (1).

Diagnostic Yield (1-2)

WES

27%

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Chromosomal Microarray

11-14%

 

Gene Panels

17% ​​​​​

WES Diagnostic Yield

Up to 70% (1)

Isolated short stature

15%

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Syndromic short stature

26% ​

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Body disproportion or skeletal abnormalities

70%

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With intellectual disability

57%

 

Parents with short stature

38% ​

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Small for gestational age

64%

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Recurrently identified genes: PTPN11, NF1, COL2A1, ACAN, and FGFR3.

  1. Diagnostic yield of genetic testing in children with short stature: a systematic review.  European Journal of Endocrinology, 2026, 194, S15–S24

  2. Molecular Diagnostic Yield of Exome Sequencing and Chromosomal Microarray in Short Stature.  A Systematic Review and Meta-Analysis. JAMA Pediatr. 2023;177(11):1149-1157.

Optional Precocious Puberty Analysis

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Precocious puberty is the development of pubertal changes before age 8 in girls or age 9 in boys. Nova offers optional analysis of genes associated with central precocious puberty and related genetic conditions, including genes involved in the regulation of pubertal timing.

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Genetic testing may help identify an underlying cause, particularly when early puberty runs in the family or occurs with other developmental, neurological, growth, or physical findings. Testing complements, but does not replace, endocrine evaluation, hormone testing, bone-age assessment, or brain imaging when clinically indicated.

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INDICATIONS FOR TESTING​

Severe short stature

Height below −3 SDS, or marked deviation from the child’s expected family height.

Growth faltering

A sustained decline in height SDS or crossing of growth percentiles after measurement error and common secondary causes are considered.

Disproportion or skeletal findings

Abnormal sitting-height-to-height and arm-span-to-height ratios, limb disproportion, deformity, joint findings, or suggestive radiographs.

Syndromic features

Dysmorphic features, congenital anomalies, microcephaly, macrocephaly, developmental differences, intellectual disability, or multisystem findings.

Persistent short stature after SGA birth

Birth weight or length below −2 SDS without adequate catch-up growth, particularly when an imprinting disorder or syndrome is suspected.

Unexplained endocrine phenotype

Severe growth-hormone deficiency, pituitary structural abnormalities, or other findings suggesting a monogenic endocrine disorder.

Unresolved evaluation

Persistent short stature after clinically appropriate endocrine, nutritional, gastrointestinal, renal, inflammatory, and other secondary causes have been assessed.

Precocious Puberty ​

  • Early or rapidly progressive pubertal development

  • Precocious puberty accompanied by short stature, markedly advanced bone age, or reduced predicted adult height​

  • A family history of early puberty affecting multiple relatives, particularly through the paternal side of the family

  • An unexplained presentation after appropriate endocrine and clinical evaluation, suspected peripheral precocious puberty or another inherited endocrine disorder

PRE-TEST PHENOTYPING

Variant interpretation starts with the growth assessment.

Growth data & Body proportions

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Serial height and weight, growth velocity, birth size, pubertal stage, skeletal asymmetry or deformity, head circumference, arm span.​

Family context

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Mid-parental height, consanguinity, parental timing of puberty, and a three-generation pedigree.​

Associated features

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Development, dysmorphism, congenital anomalies, vision, hearing, cardiac, renal, gastrointestinal, immune, and neurological findings.​

Prior investigations & Treatment history

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Bone age and clinically directed endocrine, metabolic, inflammatory, renal, gastrointestinal, cytogenetic, methylation, or imaging findings. Previous or current growth-promoting therapy & response.​

NOVA GUIDED CLINICAL FORM

Convert the growth presentation into an interpretable phenotype.

Nova’s form and genetic counsellor review capture growth trajectory, auxology, family history, examination, associated findings, and prior testing in a structured format.

 

This helps prioritize relevant genes and distinguish a plausible disease association from a weakly matched finding.

CLINICAL UTILITY

How an etiologic diagnosis may change care.

Etiologic diagnosis

Identify a pathogenic or likely pathogenic variant that may explain all or part of the patient’s presentation.

Prognosis, anticipatory comorbidities

Clarify expected clinical features and identify associated conditions that may emerge over time.

Management, surveillance

Support condition-specific surveillance, referrals, treatment discussions, and multidisciplinary care when clinically indicated.

May inform growth therapy discussions

Some diagnoses may support growth-promoting therapy (such as SHOX gene deficiencies, Turner syndrome, or specific growth hormone axis mutations); others may predict limited response, require caution, or make treatment inappropriate.

Recurrence counselling

Refine reproductive risk according to the diagnosis, inheritance pattern, penetrance, and possibility of germline mosaicism.

Diagnostic efficiency

​Reduce serial testing and repeated referrals when a genomic diagnosis resolves a complex presentation.

RECURRANCE RISK

De novo findings

A variant present in the child but absent from parental samples may support pathogenicity and generally lowers, but does not eliminate recurrence risk because germline mosaicism may occur.

Inherited findings

Recurrence risk depends on the mode of inheritance, penetrance, and parental phenotype. Some autosomal-dominant findings may confer a 50% transmission probability.

TEST PROCESS & LABORATORY

Clinical sequencing through the Broad Clinical Labs

BCL

Broad Clinical Labs

Clinical sequencing is performed by Broad Clinical Labs, a CLIA-certified and CAP-accredited subsidiary of the Broad Institute.

Accreditations:

  • CLIA Number: 22D2055652

  • ​CAP Number: 8707596​

1

Physician order

Select WES and complete Nova’s guided clinical form (physician attestation).

2

Counsellor review

Our genetic counsellor reviews, structures the phenotypes, and prepare HPO terms before analysis and interpretation.

3

At-home collection

The family receives a buccal-swab kit for cheek-swab collection and return shipment to the clinical laboratory.

4

Clinical sequencing

Sequencing is performed by Broad Clinical Labs in its CLIA-certified and CAP-accredited laboratory.

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Interpretation and reporting

Findings are correlated with the phenotype and reported with clinical context, limitations, and appropriate next steps.

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Result review

The physician receives the report; physician summary written for primary care teams, and genetic counselor summary in everyday English are included.

CLINICAL REPORT

Four principal result categories

Pathogenic/Likely Pathogenic
01
Positive Finding

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A pathogenic or likely pathogenic variant may establish or support an etiologic diagnosis.​

Potential value

Diagnosis, prognosis, surveillance, referrals, condition-specific management, family testing, or reproductive counselling.

NEG
02
Negative finding

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No reportable disease-causing variant was identified with the current test and knowledge.

Clinical implication

No disease-causing single nucleotide variants in coding regions was detected. A genetic etiology is not excluded. Consider alternative tests such as WGS, and future reanalysis of WES data.

VUS
03
Uncertain finding

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Variant of uncertain clinical significance (VUS) was detected. Available evidence is insufficient to classify the variant as disease-causing or benign.

Clinical implication

Do not use a VUS alone for diagnosis or major management decisions. Segregation, phenotype evolution, functional evidence, or future reanalysis may help.

PHENOTYPE-CORRELATED REVIEW

Selected uncertain findings may still deserve clinical attention.

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Nova manually correlates selected VUS with the patient’s phenotype and current evidence.

 

Findings with a meaningful clinical fit and emerging evidence may be highlighted for conservative follow-up or reassessment of evolving comorbidities. They remain uncertain and do not independently justify treatment.

WES limitations​

  • WES may not reliably detect every copy-number or structural variant, methylation or imprinting disorder, balanced rearrangement, repeat expansion, low-level mosaic variant, deep intronic variant, mitochondrial variant, or technically difficult region.

  • Karyotype, chromosomal microarray, methylation testing, SHOX-focused dosage analysis, skeletal imaging, or other targeted assays may still be indicated.

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Turner syndrome 

  • ​If Turner syndrome is suspected, consider karyotyping as the initial genetic test.

  1. International guideline on genetic testing of children with short stature. European Journal of Endocrinology. 2026;194(2) -R36.

  2. Focused revision: ACMG practice resource - genetic evaluation of short stature. Genetics in Medicine. 2021;23(5):813 -815.

  3. International consensus guideline on small for gestational age: Etiology and management from infancy to early adulthood. Endocrine Reviews. 2023;44(3):539–565.

ORDERING & SUPPORT

Physician ordered. Family self-pay. No insurance submission.

Physician responsibilities

  • Complete Nova’s guided clinical form (requisition form)

  • Enter clinical indications and select the appropriate test

 

For parents/patients

  • Discuss possible positive, negative, and uncertain results

  • Review limitations, consent, and family implications

  • Receive and disclose the clinical report

Clinical report is emailed or fax to the ordering physician​

Nova support

  • Pre-test physician support - indications for testing, singleton vs trio/duo testing, WES vs WGS, test limitations

  • Physician-friendly interpretation and next-step summary

  • Parent explanation written in everyday English

  • Post-test genetic counselling and reanalysis options available

Testing Available in All U.S. States Except New York

Nova currently accepts physician orders for patients residing in all U.S. states except New York.

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Testing is not currently available to New York residents.

Genetic Counseling Available

Genetic counseling is available to help patients and families understand what the results mean, family testing, or future family planning.

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Genetic counseling is available through DNAvisit, which provides genetic counseling services nationwide. A 30-minute session costs approximately $150. Appointment information will be provided with the genetic test report.

Fees are set by DNAvisit and are subject to change. ​

Billing and refund policy

This is a self-pay service. The standard WES price is $399, plus $70 for the buccal-swab kit and round-trip shipping. Patients or families pay directly through the Nova website.

 

Nova does not verify insurance benefits, request prior authorization, or submit claims.

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Tests are non-refundable after online ordering. If the sample fails quality control and testing cannot proceed, the test fee will be refunded, but the $70 shipping fee will not.

EVIDENCE

Evidence informing the short-stature clinical pathway

The 2026 international guideline supports WES as a first-line broad genetic testing for selected children with short stature after initial clinical evaluation and exclusion of non-genetic causes.

 

The chance of identifying a genetic cause varies substantially by phenotype: 

Fewer than 15% in children with isolated short stature, compared with up to 70% in those with syndromic short stature or suspected skeletal dysplasia. Careful assessment of growth pattern, body proportions, family history, dysmorphic features, neurodevelopment, radiographic findings, and laboratory results helps identify children most likely to benefit from genetic testing.

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The ACMG recommends a phenotype-directed testing pathway:

This may include karyotyping for girls with persistent or progressive short stature, chromosomal microarray for suspected chromosomal abnormalities, targeted testing for a recognizable disorder, skeletal assessment for disproportionate short stature, and a multigene panel or exome sequencing when the cause remains unclear. Methylation or uniparental-disomy testing should be considered separately when an imprinting disorder is suspected.

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Before genetic testing, the clinical evaluation should include accurate serial height measurements, growth velocity, midparental height, bone age, medical and family history, and physical examination. Endocrine, nutritional, gastrointestinal, renal, and other acquired causes should be evaluated as clinically indicated.

Guideline​​

  1. International guideline on genetic testing of children with short stature. European Journal of Endocrinology. 2026;194(2)–R36.

  2. Focused revision: ACMG practice resource - genetic evaluation of short stature. Genetics in Medicine. 2021;23(5):813–815.

  3. International consensus guideline on small for gestational age: Etiology and management from infancy to early adulthood. Endocrine Reviews. 2023;44(3):539–565.

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Diagnostic Yield

  1. Molecular diagnostic yield of exome sequencing and chromosomal microarray in short stature: A systematic review and meta-analysis. JAMA Pediatrics. 2023;177(11):1149–1157.

  2. Diagnostic yield of genetic testing in children with short stature: A systematic review. European Journal of Endocrinology. 2026;194(2)–S24.

  3. Genetic investigation of idiopathic short stature in the endocrinology practice: The Mayo Clinic experience. Genetics in Medicine. 2022;24(3 Suppl)–S95. Conference abstract.

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References

  1. ​Stratifying the genetic aetiology in children born small for gestational age with persistent short stature (SGA-SS). Journal of the Endocrine Society. 2021;5(Suppl 1)–A686. Conference abstract.

  2. Rare copy number variants are a common cause of short stature. PLOS Genetics. 2013;9(3).

  3. Genomic insights into short stature in children born small for gestational age: A Korean multicenter exome study. The Journal of Clinical Endocrinology & Metabolism. 2026;111(3):622–635.

  4. Genetics of idiopathic short stature: Insights into growth regulation. Journal of Pediatric Endocrinology and Diabetes. 2025;5(1):12–21.

  5. Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature. Genetics in Medicine. 2018;20(6):630–638.

  6. Evaluation of short and tall stature in children. American Family Physician. 2015;92(1):43–50.​

 

Recommendations from Professional Societies/Organizations​

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2026 International Guideline on Genetic Testing of Children with Short Stature.

  • The guideline emphasizes advanced molecular techniques, establishing whole exome sequencing (WES) as the highest-yielding modality for evaluating childhood short stature.

  • This guideline is endorsed by the:

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  1. European Society for Paediatric Endocrinology

  2. Pediatric Endocrine Society

  3. Latin American Society of Pediatric Endocrinology

  4. Chinese Society of Pediatric Endocrinology and Metabolism

  5. Japanese Society for Pediatric Endocrinology

  6. European Society of Human Genetics

  7. Japan Society of Human Genetics

  8. Human Genetics Society of Australasia

 

  • The guideline recommends completing a clinical evaluation and excluding non-genetic causes before genetic testing. Genetic testing is recommended when the history, physical examination, growth measurements, radiographs, or laboratory findings suggest an increased likelihood of a genetic cause.

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American College of Medical Genetics and Genomics

  • The ACMG recommends a phenotype-directed genetic evaluation. Its pathway includes:

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  • Karyotyping as part of the initial evaluation for girls with persistent or progressive short stature

  • Chromosomal microarray for suspected chromosomal abnormalities or copy-number variants

  • Targeted testing when a recognizable disorder is suspected

  • SHOX analysis when clinically indicated

  • A multigene panel or WES when the cause remains unclear

  • Methylation or uniparental-disomy testing when an imprinting disorder is suspected

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International Consensus Guideline on Small for Gestational Age

 

  • Developed by experts representing 10 pediatric endocrine societies, this guideline recommends considering genetic testing in children born small for gestational age who have persistent short stature, with or without skeletal disproportion, when no other cause has been identified.

  • Evaluation by a clinical geneticist is particularly recommended when the child also has:

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  • Dysmorphic features

  • Major congenital anomalies

  • Microcephaly

  • Developmental delay or intellectual disability

  • Signs of skeletal dysplasia

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  • Specific methylation and uniparental-disomy testing should be used when Silver–Russell syndrome or another imprinting disorder is suspected. WES or a multigene panel may be considered when a monogenic disorder is likely.

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