1q21.1 Recurrent Deletion

Clinical characteristics: The 1q21.1 recurrent deletion itself does not lead to a clinically recognizable syndrome, as some persons with the deletion have no obvious clinical findings. Others have variable findings that most commonly include mildly dysmorphic but nonspecific facial features (>75%), mild intellectual disability or learning disabilities (25%), microcephaly (43%), and eye abnormalities (26%). Other findings can include cardiac defects, genitourinary anomalies, skeletal malformations, joint laxity, and seizures (~23%). Psychiatric and behavioral abnormalities can include autism spectrum disorder, attention-deficit/hyperactivity disorder, and sleep disturbances. Sensorineural hearing loss and recurrent infections /otitis media are rare.

Diagnosis/testing: The diagnosis of the 1q21.1 recurrent deletion is established by the detection of the recurrent distal heterozygous deletion between BP3 and BP4 at the approximate position of chr1:147105904-147917509 in the reference genome (NCBI Build 38).

Management: Treatment of manifestations: Feeding therapy to address poor growth, with a low threshold for a clinical feeding evaluation and/or radiographic swallowing study when there are clinical signs or symptoms of dysphagia. Standard treatment for gastroparesis, constipation, gastroesophageal reflux disease, developmental delay / intellectual disability, eye anomalies/refractive error, congenital heart disease, epilepsy, tremors/tics, hernia, cryptorchidism, skeletal anomalies, and hearing loss.

Surveillance: At each visit: measure growth parameters; monitor for constipation; assessment for anxiety, ADHD, and behavioral problems; monitor for developmental progress and educational needs; monitor those with seizures as clinically indicated; assess for new manifestations, such as seizures, tremors, or tics; and assess motility and self-help skills. At least annually or as clinically indicated: ophthalmology evaluation and audiology evaluation.

Genetic counseling: The 1q21.1 recurrent deletion is inherited in an autosomal dominant manner. Between 18% and 35% of deletions occur de novo. The deletion can be inherited from either parent; a parent with the deletion may show a normal phenotype or an abnormal phenotype that is similar to but usually less severe than that of the parent's child. Each child of an individual with the 1q21.1 recurrent deletion has a 50% chance of inheriting the deletion; it is not possible to predict the phenotype in offspring who inherit the deletion. Recurrence risk for future pregnancies for parents who do not have the deletion is low (probably <1%) but greater than that of the general population because of the possibility of germline mosaicism.