Pituitary stalk interruption syndrome: genes and variants

Genes linked to Pituitary stalk interruption syndrome

• DNMT1: DNA (cytosine-5)-methyltransferase 1

  It copies existing DNA methylation patterns during replication and also contributes to chromatin regulation and neuronal maintenance. Dominant pathogenic variants can cause hereditary sensory neuropathy with dementia and hearing loss or a cerebellar ataxia-deafness-narcolepsy syndrome.

  1 disease-causing and 0 uncertain variants in DNMT1 are linked to Pituitary stalk interruption syndrome.

• SMARCA2: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2

  It provides ATP-dependent nucleosome remodeling activity to selected SWI/SNF complexes and helps control transcriptional access to chromatin. Heterozygous pathogenic variants cause Nicolaides-Baraitser syndrome or, through distinct mechanisms, blepharophimosis-intellectual-disability syndrome.

  1 disease-causing and 0 uncertain variants in SMARCA2 are linked to Pituitary stalk interruption syndrome.

Weakly linked (only a few uncertain records): ARID1B, CHD7, FGFR3, PTCH1 and RAF1.

Known disease-causing variants in Pituitary stalk interruption syndrome

Same protein, different disease

• Nicolaides-Baraitser syndrome is also caused by SMARCA2 variants; they fall mostly in different places as the Pituitary stalk interruption syndrome variants (50 disease-causing).
• Blepharophimosis-impaired intellectual development syndrome is also caused by SMARCA2 variants; they fall mostly in different places as the Pituitary stalk interruption syndrome variants (8 disease-causing).
• SMARCA2-related BAFopathy is also caused by SMARCA2 variants; they fall mostly in different places as the Pituitary stalk interruption syndrome variants (7 disease-causing).
• Autosomal dominant cerebellar ataxia, deafness and narcolepsy is also caused by DNMT1 variants; they fall mostly in different places as the Pituitary stalk interruption syndrome variants (5 disease-causing).
• Hereditary sensory neuropathy-deafness-dementia syndrome is also caused by DNMT1 variants; they fall mostly in different places as the Pituitary stalk interruption syndrome variants (3 disease-causing).

Diseases related to Pituitary stalk interruption syndrome

• Nicolaides-Baraitser syndrome, also linked to SMARCA2
• Acute myeloid leukemia, also linked to DNMT1
• Blepharophimosis-impaired intellectual development syndrome, also linked to SMARCA2
• Spastic ataxia, also linked to DNMT1
• SMARCA2-related BAFopathy, also linked to SMARCA2
• Autosomal dominant cerebellar ataxia, deafness and narcolepsy, also linked to DNMT1
• Myelodysplastic syndrome, also linked to DNMT1
• Hereditary sensory neuropathy-deafness-dementia syndrome, also linked to DNMT1

Frequently asked questions

Which genes are linked to Pituitary stalk interruption syndrome?

In CATVariant, Pituitary stalk interruption syndrome is linked to 2 analyzed proteins: DNMT1 (DNA (cytosine-5)-methyltransferase 1) and SMARCA2 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2).

How many genetic variants are linked to Pituitary stalk interruption syndrome?

7 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 5 are of uncertain significance or have conflicting reports.

Which uncertain variants in Pituitary stalk interruption 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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