Disease characteristics. The KdVS is characterized by developmental delay/intellectual disability, neonatal/childhood hypotonia, dysmorphisms, congenital malformations, and behavioral features. Global psychomotor developmental delay is noted in all individuals from an early age. The majority of individuals with the KANSL1-related intellectual disability syndrome function in the mild to moderate range of intellectual disability. Other findings include epilepsy, congenital heart defects, renal and urologic anomalies, and cryptorchidism. Behavior in most is described as friendly, amiable, and cooperative.
Diagnosis/testing. The syndrome can be caused by a 500- to 650-kb heterozygous deletion at chromosome 17q21.31 that includes KANSL1 or a heterozygous intragenic mutation in KANSL1. Molecular genetic testing that detects these abnormalities is available on a clinical basis. Note: The 17q21.31 microdeletion cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques.
Management. Treatment of manifestations: Physiotherapy for feeding problems and motor delay, speech therapy and other interventions to augment communication, educational programs directed to specific disabilities identified. Routine treatment of: epilepsy; scoliosis, hip dislocation, and positional deformities of the feet; cryptorchidism; cardiac, renal, and urologic problems.
Surveillance: Routine ophthalmologic examinations for hypermetropia and strabismus; monitoring for progressive spine deformities.
Genetic counseling. The KdVS, caused by a microdeletion or a mutation of KANSL1, is inherited in an autosomal dominant manner, but to date almost all cases result from a de novo deletion or KANSL1 mutation. Thus, most affected individuals represent simplex cases, i.e., a single occurrence in a family. The recurrence risk for future pregnancies is low (probably <1%) but greater than that of the general population because of the possibility of germline mosaicism in one of the parents. No individuals with KANSL1-related intellectual disability syndrome have been known to reproduce. Prenatal testing is technically feasible, but the likelihood of recurrence in families who have had an affected child is low.