NT Genetics Registry

About the NT Genetic Registry – please scroll down to view the full list of conditions.

Many people, including some medical professionals, still believe that NT is a marker only for trisomy 21 (Down syndrome). This is a common misconception.

In fact, there are more than 3,000 scientific publications describing associations between increased NT and a wide range of genetic conditions and pathogenic gene variants. Surprisingly, this information has never been fully systematised.

We have undertaken extensive work to compile and organise this comprehensive registry of conditions and relevant genetic variants. The registry currently includes approximately 650 conditions and gene variants (mutations). We have chosen not to exclude certain duplications, as these may reflect important genotype–phenotype interactions associated with increased NT. Some conditions are associated with multiple genes, while a single gene may also be linked to several distinct genetic syndromes.

Overall, we have identified around 300 individual genetic variants associated with the increased NT phenotype.

We recognise that the registry is not yet exhaustive and will continue to be reviewed, updated, and expanded on a regular basis. If you are aware of a condition or gene variant that is not currently included, please contact us with the relevant reference. We would be pleased to review it for inclusion.

Please note: this registry focuses on genetic causes and does not include structural, non-genetic conditions associated with increased NT, such as heart defects or VACTERL syndrome.

What groups of diseases are associated with increased NT?

Increased nuchal translucency (NT) can be linked to a wide range of genetic abnormalities, which can be broadly divided into several main groups:

1. Aneuploidies – conditions caused by an abnormal number of chromosomes, such as trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome).
2. Sex chromosome anomalies – for example, Turner syndrome (45,X), Klinefelter syndrome (47,XXY), and other X/Y chromosome imbalances.
3. Structural chromosomal rearrangements – including microdeletions, microduplications, and other copy number variants (CNVs) that affect chromosomal segments rather than whole chromosomes. Examples include 22q11 deletion syndrome (DiGeorge syndrome) and 1p36 deletion syndrome.
4. Monogenic (single-gene) disorders – caused by mutations in a single gene. These represent a very large and diverse group, including conditions such as Noonan syndrome and other RASopathies, skeletal dysplasias, metabolic disorders, and neuromuscular syndromes. They may follow dominant, recessive, or X-linked inheritance, but most are due to de novo mutations (new changes not inherited from parents).

Together, these categories account for hundreds of distinct conditions associated with increased NT, reflecting the wide genetic diversity underlying this ultrasound finding.

What are the most common monogenic conditions?

Commonest single-gene (monogenic) disorders associated with increased nuchal translucency (NT):

• Noonan syndrome and related RASopathies – PTPN11, SOS1, RAF1, KRAS, NRAS, HRAS, BRAF, MAP2K1, MAP2K2, RIT1, SHOC2, CBL, RRAS, MRAS, LZTR1
• Cardio-facio-cutaneous (CFC) syndrome – BRAF, MAP2K1, MAP2K2
• Costello syndrome – HRAS
• Neurofibromatosis type 1 / Legius syndrome – NF1, SPRED1
• CHARGE syndrome – CHD7
• Turner-like lymphatic dysplasia – FLT4 (VEGFR3), CCBE1, ADAMTS3, PIEZO1, FOXC2
• Kabuki syndrome – KMT2D, KDM6A
• Rubinstein–Taybi syndrome – CREBBP, EP300
• Rett syndrome – MECP2
• Coffin–Siris and related SWI/SNF complex disorders – ARID1B, SMARCA4, SMARCB1
• Craniosynostosis syndromes (Apert, Crouzon, Muenke, Saethre–Chotzen) – FGFR2, FGFR3, TWIST1, TCF12
• Thanatophoric dysplasia – FGFR3
• Stickler and Kniest syndromes – COL2A1, COL11A1, COL11A2
• Marfan syndrome – FBN1
• Ehlers–Danlos syndromes – PLOD1, TNXB
• Osteogenesis imperfecta – COL1A1, COL1A2
• Tuberous sclerosis complex – TSC1, TSC2
• Greig cephalopolysyndactyly / Pallister–Hall syndrome – GLI3
• Joubert and Meckel–Gruber syndromes – TMEM67, CC2D2A, CEP290
• Smith–Lemli–Opitz syndrome – DHCR7
• Lysosomal storage disorders (e.g. Gaucher, Krabbe, Tay–Sachs) – GBA, GALC, HEXA
• Branchio-oto-renal spectrum disorders – EYA1, SIX1, GATA3, CDH1
• Ectrodactyly–ectodermal dysplasia–clefting (EEC) syndrome – TP63
• Cortical malformation syndromes – TUBA1A, DYNC1H1, KIF5C