Beckwith-Wiedemann syndrome: genes and variants

Genes linked to Beckwith-Wiedemann syndrome

• CDKN1C: Cyclin-dependent kinase inhibitor 1C

  It restrains embryonic and placental cell proliferation and is subject to parent-of-origin-specific genomic imprinting. Loss of maternal expression contributes to Beckwith-Wiedemann syndrome, whereas gain-of-function variants can cause growth-restriction syndromes such as IMAGe syndrome.

  4 disease-causing and 144 uncertain variants in CDKN1C are linked to Beckwith-Wiedemann syndrome.

• NSD1: Histone-lysine N-methyltransferase, H3 lysine-36 specific

  It regulates developmental transcription through chromatin modification, including H3K36 methylation. Haploinsufficiency causes Sotos syndrome with childhood overgrowth, characteristic facial features, and developmental delay, while somatic rearrangements occur in some leukemias.

  3 disease-causing and 2 uncertain variants in NSD1 are linked to Beckwith-Wiedemann syndrome.

• KCNQ1: Potassium voltage-gated channel subfamily KQT member 1

  The protein forms the pore of a voltage-gated potassium channel that helps set electrical activity in heart muscle. Its partnerships with KCNE subunits also support normal function in the inner ear and other tissues, while KCNQ1 variants are linked to long-QT and short-QT syndromes.

  0 disease-causing and 6 uncertain variants in KCNQ1 are linked to Beckwith-Wiedemann syndrome.

Known disease-causing variants in Beckwith-Wiedemann syndrome

Same protein, different disease

• IMAGe syndrome is also caused by CDKN1C variants; they fall mostly in different places as the Beckwith-Wiedemann syndrome variants (3 disease-causing).
• Sotos syndrome is also caused by NSD1 variants; they fall mostly in different places as the Beckwith-Wiedemann syndrome variants (82 disease-causing).

Diseases related to Beckwith-Wiedemann syndrome

• Long QT syndrome, also linked to KCNQ1
• Alzheimer disease, also linked to CDKN1C
• Cardiac arrhythmia, also linked to KCNQ1
• Sotos syndrome, also linked to NSD1
• Type 2 diabetes mellitus, also linked to KCNQ1
• Short QT syndrome type 3, also linked to KCNQ1
• Acute myeloid leukemia, also linked to NSD1
• Epilepsy, also linked to KCNQ1
• Atrial fibrillation, familial, 10, also linked to KCNQ1
• Monogenic hearing loss, also linked to KCNQ1
• Weaver syndrome, also linked to NSD1
• Diabetes mellitus, also linked to KCNQ1

Frequently asked questions

Which genes are linked to Beckwith-Wiedemann syndrome?

In CATVariant, Beckwith-Wiedemann syndrome is linked to 3 analyzed proteins: CDKN1C (Cyclin-dependent kinase inhibitor 1C), NSD1 (Histone-lysine N-methyltransferase, H3 lysine-36 specific) and KCNQ1 (Potassium voltage-gated channel subfamily KQT member 1).

How many genetic variants are linked to Beckwith-Wiedemann syndrome?

180 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 152 are of uncertain significance or have conflicting reports.

Which uncertain variants in Beckwith-Wiedemann syndrome look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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