Comprehensive Short Stature Syndrome Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: MA2101

The Blueprint Genetics Comprehensive Short Stature Syndrome Panel is a 61 gene test for genetic diagnostics of patients with clinical suspicion of short stature and associated syndromes.

Numerous monogenic causes of growth disorders have been identified. This panel covers several disorders associated with short stature with autosomal recessive and dominant modes of inheritance. This comprehensive Panel includes (but is not limited to) disorders covered by the subpanels: 3-M Syndrome / Primordial Dwarfism Panel, Meier-Gorlin Syndrome Panel and Seckel Syndrome Panel. This Panel is part of the Comprehensive Skeletal / Malformation Syndrome Panel.

About Short Stature Syndromes

The clinical phenotypes of the disorders covered by this panel range in the severity of growth retardation and microcephaly, as well as in the degree of developmental delay, but there can be significant clinical overlap among syndromes. In addition to the disorders covered by the sub-panels, this comprehensive panel covers several other diseases associated with short stature, such as growth delay due to insulin-like growth factor I resistance or IGF1 deficiency (mutations in IGF1R and IGF1), hypothyroidism due to deficient transcription factors involved in pituitary development or function (HESX1, LHX3, LHX4, POU1F1 and PROP1), Rubinstein-Taybi syndrome (CREBBP and EP300) and different forms of disproportionate short stature. Disproportionate short stature can manifest itself as short-limbed dwarfism or short-trunk dwarfism. Achondroplasia (autosomal dominant, mutations is FGFR3) is the most common form of disproportionate growth retardation, its estimated incidence is at about 1/25,000 live births worldwide.

Identification of rare monogenic causes of short stature is critical since the genetic diagnosis may alert the clinician to other medical comorbidities for which the patient is at risk. For example, a male patient with 3-M syndrome will need to be monitored for the development of hypogonadism. Based on genetic studies in children with severe short stature of unknown etiology it has been suggested that monogenic causes of short stature are underdiagnosed in the pediatric endocrine clinic. Factors that increase the likelihood for a monogenic cause of short stature are severe GH deficiency, multiple pituitary hormone deficiency, unequivocal GH insensitivity, small for gestational age without catch-up growth, additional congenital anomalies or dysmorphic features, evidence of a skeletal dysplasia, associated intellectual disability, microcephaly and height below −3 SD.


Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Comprehensive Short Stature Syndrome Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
AKT1Proteus syndrome, Cowden syndromeAD39
ATRCutaneous telangiectasia and cancer syndrome, Seckel syndromeAD/AR613
BMP2Brachydactyly type A2AD126
BMP4Microphthalmia, syndromic, Orofacial cleftAD942
BMPR1A*Polyposis, juvenile intestinalAD38108
CDC6Meier-Gorlin syndrome (Ear-patella-short stature syndrome)AR13
CDT1Meier-Gorlin syndrome (Ear-patella-short stature syndrome)AR68
CENPJSeckel syndrome, MicrocephalyAR236
CEP63Seckel syndromeAR42
CEP152Seckel syndrome, MicrocephalyAR1317
CREBBPRubinstein-Taybi syndromeAD103332
CUL73-M syndrome, Yakut short stature syndromeAR1868
DHCR7Smith-Lemli-Opitz syndromeAR42194
EP300Rubinstein-Taybi syndromeAD2143
EYA1Otofaciocervical syndrome, Branchiootic syndrome, Branchiootorenal syndromeAD33186
FGD1Aarskog-Scott syndrome, Mental retardation, syndromicXL1842
FGF3Deafness, congenital with inner ear agenesis, microtia, and microdontiaAR1220
FGFR3Lacrimoauriculodentodigital syndrome, Muenke syndrome, Crouzon syndrome with acanthosis nigricans, Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome, Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia type 1, Thanatophoric dysplasia type 2, SADDANAD/AR4768
FOXL2Premature ovarian failure, Blepharophimosis, epicanthus inversus, and ptosisAD69203
GH1*Isolated growth hormone deficiency, Kowarski syndromeAD/AR2498
GHRGrowth hormone insensitivity syndrome (Laron syndrome)AD/AR32100
GHRHRIsolated growth hormone deficiencyAR1347
GLI2Culler-Jones syndromeAD1674
HESX1Septooptic dysplasia, Pituitary hormone deficiency, combinedAR/AD1125
IGF1Insulin-like growth factor I deficiencyAR412
IGF1RInsulin-like growth factor I, resistanceAD/AR562
IGFALSInsulin-like growth factor-binding protein, acid-labile subunit, deficiencyAR528
INSRHyperinsulinemic hypoglycemia, familial, Rabson-Mendenhall syndrome, Donohoe syndromeAD/AR35175
IRS1Diabetes mellitus, noninsulin-dependentAD/AR223
KRAS*Noonan syndrome, Cardiofaciocutaneous syndromeAD4638
LHX3Pituitary hormone deficiency, combinedAR914
LHX4Pituitary hormone deficiency, combinedAD917
NIPBLCornelia de Lange syndromeAD246404
NOTCH2*Alagille syndrome, Hajdu-Cheney syndromeAD2156
NR5A1Adrenocortical insufficiency, Premature ovarian failure, 46,XY sex reversalAD/AR21137
OBSL13-M syndromeAR922
ORC1Meier-Gorlin syndrome (Ear-patella-short stature syndrome)AR99
ORC4Meier-Gorlin syndrome (Ear-patella-short stature syndrome)AR135
ORC6Meier-Gorlin syndrome (Ear-patella-short stature syndrome)AR55
OTX2Microphthalmia, syndromic, Pituitary hormone deficiency, combined, Retinal dystrophy, early-onset, and pituitary dysfunctionAD1665
PCNTMicrocephalic osteodysplastic primordial dwarfismAR3082
PITX2Axenfeld-Rieger syndrome, Ring dermoid of cornea, Iridogoniodysgenesis, Peters anomalyAD1385
POU1F1Pituitary hormone deficiency, combinedAR1942
PROP1Pituitary hormone deficiency, combinedAR1934
PTCH1Basal cell nevus syndromeAD46348
PTPN11LEOPARD syndrome, Noonan syndrome, MetachondromatosisAD122129
RAF1LEOPARD syndrome, Noonan syndrome, Dilated cardiomyopathy (DCM)AD3742
RBBP8Seckel syndrome, Jawad syndromeAR45
RNU4ATACRoifman syndrome, Microcephalic osteodysplastic primordial dwarfism type 1, Microcephalic osteodysplastic primordial dwarfism type 3AR1518
SHHHoloprosencephaly, Microphthalmia with colobomaAD29212
SHOX*Leri-Weill dyschondrosteosis, Langer mesomelic dysplasia, Short statureXL/PAR23366
SMC1ACornelia de Lange syndromeXL3954
SOS1Noonan syndromeAD4166
SOX2*Microphthalmia, syndromicAD2494
STAT5B*Growth hormone insensitivity with immunodeficiencyAR511
TBX3Ulnar-Mammary syndromeAD521
TBX19Adrenocorticotropic hormone deficiencyAR526
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (; HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, The list of associated (gene specific) phenotypes are generated from CDG ( or Orphanet ( databases.

Blueprint Genetics offers a Comprehensive Short Stature Syndrome Panel that covers classical genes associated with 3-M syndrome, Jawad syndrome, meier-Gorlin syndrome (Ear-patella-short stature syndrome), microcephalic primordial dwarfism disorders (MOPD), Seckel syndrome, short stature and associated syndromes and short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (, the NHLBI GO Exome Sequencing Project (ESP;, the Exome Aggregation Consortium (ExAC;, ClinVar database of genotype-phenotype associations ( and the Human Gene Mutation Database ( The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (, Polyphen (, and Mutation Taster (

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes


ICD codes

Commonly used ICD-10 codes when ordering the Comprehensive Short Stature Syndrome Panel

Q87.1Short stature and associated syndromes

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

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