Table 3.

Disorders Associated with Germline Intragenic ELN, GTF2IRD1, and NCF1 Pathogenic Variants

GeneDisorderComment
ELN Autosomal dominant cutis laxa type 1 (ADCL1) (OMIM 123700)Generalized cutis laxa of variable severity. Aortic root dilatation & emphysema may occur. (See LTBP4-Related Cutis Laxa.)
Autosomal dominant supravalvuar aortic stenosis (SVAS) (OMIM 185500)Persons w/SVAS should be evaluated to determine if WS or autosomal dominant SVAS is the appropriate diagnosis. Persons w/autosomal dominant SVAS typically have only connective tissue abnormalities, & thus do not have WS.
GTF2IRD1 GTF2IRD1-related neurodevelopmental disorderReported in 1 family to date. Biallelic GTF2IRD1 variants were reported in 2 brothers w/autism, severe neurodevelopmental delay (incl seizures), & dysmorphic facial features (different from those in WS); heterozygous parents & sibs did not exhibit signs or symptoms of the presumably autosomal recessive syndrome [Cummings & Starr 2023].
NCF1 Chronic granulomatous disease (CGD)Biallelic pathogenic variants cause autosomal recessive CGD, a primary immunodeficiency disorder of phagocytes resulting from impaired killing of bacteria & fungi.

WS = Williams syndrome

From: Williams Syndrome

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