Koolen-De Vries syndrome

Abstract

Clinical characteristics Koolen-de Vries syndrome (KdVS) is characterized by developmental delay / intellectual disability, neonatal/childhood hypotonia, dysmorphisms, congenital malformations, and behavioral features. Psychomotor developmental delay is noted in all individuals from an early age. The majority of individuals with KdVS function in the mild-to-moderate range of intellectual disability. Other findings include speech and language delay (100%), epilepsy (~33%), congenital heart defects (25%-50%), renal and urologic anomalies (25%-50%), and cryptorchidism (71% of males). Behavior in most is described as friendly, amiable, and cooperative. Diagnosis/testing The diagnosis of Koolen-de Vries syndrome is established in a proband who has either a heterozygous 500- to 650-kb deletion at chromosome 17q21.31 that includes KANSL1 or a heterozygous intragenic pathogenic variant in KANSL1. Note: The 17q21.31 deletion cannot be identified by analysis of G-banded chromosomes or other cytogenetic banding techniques. Management Treatment of manifestations: Physiotherapy for gross and fine motor delays; speech therapy to support early feeding challenges and communication development; educational programs directed to specific disabilities identified. Routine treatment of: vision issues / strabismus; hearing loss; cardiac, renal, and urologic problems; epilepsy; scoliosis, hip dislocation, and positional deformities of the feet; multiple nevi. Surveillance: Routine ophthalmologic examinations for hypermetropia and strabismus; monitoring for progressive spine deformities; routine monitoring for other medication complications depending on the organ system involved. Genetic counseling Koolen-de Vries syndrome, caused by a deletion at 17q21.31 or a pathogenic variant in KANSL1, is inherited in an autosomal dominant manner; to date almost all cases result from a de novo deletion or KANSL1 pathogenic variant. Thus, most affected individuals represent simplex cases (i.e., a single occurrence in a family). The recurrence risk for future pregnancies is low (probably