Williams syndrome results from a heterozygous deletion at chromosome 7q11.23 spanning the WBSCR. GeneReviews documents that 90% to 95% of affected individuals carry the 1.55 Mb deletion and 5% to 10% carry the larger 1.84 Mb deletion; deletions of 2 to 4 Mb are associated with lower cognitive ability. Within the WBSCR, ELN deletion accounts for elastin arteriopathy; deletion of GTF2I and GTF2IRD1 correlates with intellectual disability and characteristic facial features; and NCF1 inclusion within the deletion is associated with lower hypertension prevalence. Deletions arise from chromosomes of either maternal or paternal origin. Approximately 25% of unaffected transmitting parents carry a 7q11.23 inversion polymorphism associated with a recurrence risk of approximately 1 in 1,750. Most cases arise as de novo events; offspring of an affected individual carry a 50% probability of inheriting the deletion.

The diagnosis is established by identification of a heterozygous 1.5 to 1.8 Mb deletion at chromosome 7q11.23 (approximately chr7:73,330,452 to 74,728,172, NCBI Build 38). GeneReviews documents that this deletion is not identifiable by routine G-banded chromosome analysis. Chromosomal microarray (CMA) using oligonucleotide or SNP genotyping arrays is the primary diagnostic method and can determine deletion size based on probe density in the 7q11.23 region. Most individuals with WS are identified through CMA performed during evaluation for developmental delay, intellectual disability, or autism spectrum disorder. Targeted deletion analysis by fluorescence in situ hybridization (FISH) using a 7q11.23-directed probe provides a reliable alternative when CMA is unavailable and is used for testing at-risk relatives of confirmed probands.

No FDA-approved pharmacologic treatments are documented in this packet for Williams syndrome. Specialty management of specific manifestations is described in GeneReviews published clinical practice guidelines. Cardiovascular management involves specialist cardiologist evaluation; SVAS is surgically corrected in approximately 30% of affected individuals, and hypertension is managed medically. GeneReviews documents a risk of myocardial insufficiency and cardiac arrest during anesthetic induction in individuals with biventricular outflow tract obstruction, with published guidelines addressing sedation and anesthesia risk management for this condition. GeneReviews identifies multivitamin preparations containing vitamin D as agents to avoid in children with Williams syndrome, noting that all pediatric multivitamin formulations contain this agent. Developmental delay and intellectual disability are addressed through early intervention programs, special education, and vocational training, with speech-language therapy, physical therapy, and occupational therapy as documented therapeutic modalities. Pharmacologic treatment for ADHD and anxiety is documented as required in approximately 50% of individuals, with behavioral counseling and psychotropic medication as described approaches. Melatonin therapy is noted in GeneReviews in the context of sleep disturbance management. Aggressive management of constipation is documented across all ages in GeneReviews because of the risk for early-onset diverticulosis and diverticulitis. Ocular manifestations are addressed with corrective lenses, patching, or surgical correction of strabismus.

GeneReviews documents that Williams syndrome affects individuals throughout the lifespan with ongoing surveillance requirements extending into adulthood. Cardiovascular disease, particularly SVAS and arterial stenoses, represents a primary source of morbidity. Sensorineural hearing loss prevalence increases from 60% overall to 90% in adults. Mean adult height is at the 3rd centile. Diabetes mellitus, more prevalent in adults, affects approximately 20% of individuals. Clinically significant hypercalcemia typically occurs before age 2 years. Colon diverticula are present in approximately 30%. GeneReviews notes that individuals with larger chromosomal deletions of 2 to 4 Mb display lower cognitive ability than those with typical 1.5 to 1.8 Mb deletions. Life expectancy data specific to Williams syndrome are not established in this packet.

Active clinical investigations documented in the packet include an NIMH-sponsored study characterizing the brain phenotype of children with WS (NCT01132885), a University of Pennsylvania natural history study of WS and other 7q11.23 variants (NCT06930417; completion anticipated 2045), a case-control iPSC study examining oligodendrocyte lineage development in children with WS at Qilu Hospital of Shandong University (NCT07537374; start April 2026), and a molecular mechanism study comparing cognitive differences between WS and autism spectrum disorder at the same institution (NCT07509879). A multimodal neurorehabilitation trial targeting neuroplasticity in pediatric neurodevelopmental and chromosomal disorders (NCT07493096) includes WS participants. GeneReviews notes ongoing genotype-phenotype correlation research within the WBSCR, with correlations beyond ELN currently limited by available evidence.