VIP Summary #6: Clinical phenotype of the recurrent 1q21.1 copy-number variant

Read the Abstract:

The 1q21.1 copy number variant (CNV), usually contains seven genes and is related to a variety of medical and behavioral differences, making it hard for families and medical health professionals to predict how a 1q21.1 deletion  or duplication (missing or extra genetic material in the 1q21.1 region)  will affect a child. This study looked at 19 individuals with the 1q21.1 deletion, 19 with the duplication, and 23 family members who do not have the CNV to better understand how the 1q21.1 deletion and duplication affect a person’s health and development.

In order to measure the medical and psychiatric differences in 1q21.1 CNV carriers, families participating in the Simons VIP study worked with researchers by providing medical and family history  information. Participants with the 1q21.1 CNV and their non-carrier family members also completed the same assessment battery as the family member with the deletion or duplication. The assessment battery included specific tests for IQ, memory, behavior, motor skills, and neurologic function. Participants were also evaluated for any psychiatric and autism symptoms. Individuals with a 1q21.1 CNV showed consistent differences in motor and cognitive function as well as differences in head circumference (size).

1q21.1 Deletion Carriers

People with 1q21.1 deletion had trouble with making particular sounds or processing certain words (articulation differences or phonological processing), fine motor and overall motor skills. The average verbal and nonverbal IQs for all deletion carriers were average, or typical (90-110). The most common types of psychiatric disorder identified were mood and anxiety disorders (26%).  Interestingly, the majority of individuals with 1q21.1 deletion did not meet criteria to be diagnosed with autism spectrum disorder. Some of the other medical concerns found in 1q21.1 deletion carriers are seizures (18%), hearing loss (17%), low muscle tone (33%), tremors (44%), hyperrelexia or extreme reflexes (35%), cataracts (33%), and heart problems including differences in heart rhythm (arrhythmia) and congenital heart defects (33%). Some of the physical features noticed are smaller head size (microcephaly, 22%) and short stature (50%). 


1q21.1 Duplication Carriers

People with 1q21.1 duplication had trouble with fine motor/motor skills and phonological processing, especially trouble with articulation (38%). The average verbal and nonverbal IQs were in the low-average range and a significant amount of duplication carriers were found to have intellectual disability (20%). The most common behavior problems include a clinical diagnosis for autism spectrum disorder (41%) and attention deficit hyperactivity disorder (29%). Other medical problems that were commonly found are scoliosis (36%), problems with gait (walking)/agility (39%), low muscle tone (16%), and gastric (stomach) ulcers (27%). Some of the physical features noticed are larger head size (macrocephaly 26%) and short stature (27%).

What are the differences between deletions and duplications?

When comparing 1q21.1 deletion and duplication carriers, Autism Spectrum Disorder diagnoses were more common in duplication carriers. The researchers also found that, for some specific traits, deletion and duplication carriers were “mirrors” of one another. 

  • People with duplications had larger head sizes while individuals with deletions tended to have smaller head sizes. 
  • People with duplications seemed to have more significant differences with verbal IQ and motor abilities when compared to individuals with the deletion.
  • Both deletion and duplication carriers shared many traits such as borderline cognitive (learning/understanding) abilities, motor impairments, and articulation abnormalities. 

This study showed that medical evaluation of individuals with 1q21.1 deletion or duplication should include the following:

  1. Psychiatric and neurologic evaluations at several points throughout life: childhood, adolescence, and adulthood.
  2. Evaluation by a developmental pediatrician at a young age for ASD, intellectual disability, ADHD, motor difficulties. 
  3. Hearing screening as part of well-child visits during childhood, as there were a greater proportion of children with hearing issues than in children without a 1q21.1 CNV
  4. Evaluation for both structural and rhythmic heart abnormalities.

Download the 1q21.1 DELETIONS infographic:

Download the 1q21.1 DUPLICATIONS infographic: