Clinical phenotype of the recurrent 1q21.1 copy-number variant

Original research article by Bernier R. et al. (2016).

Read the article here.

Read news coverage of the article here.

This article discusses what’s called a 1q21.1 copy number variant (CNV). This CNV can be either a deletion or a duplication of a piece of chromosome 1. (That is, there can be either missing or extra genetic material in the 1q21.1 part of chromosome 1.) The 1q21.1 CNV usually affects seven genes. It is related to a variety of medical and behavioral differences, so families and doctors have a hard time predicting how a 1q21.1 CNV will affect someone. This study looked at 19 people with the 1q21.1 deletion, 19 with the duplication, and 23 family members who do not have the CNV. The goal was to better understand how the 1q21.1 deletion or duplication affects a person’s health and development.

The study (which received support from Simons Searchlight when it was named Simons VIP) set out to measure the differences in people with a 1q21.1 CNV. Families participating in the study shared medical and family information with researchers. Also, participants with the 1q21.1 CNV and their family members took the same assessments. These assessments tested for IQ, memory, behavior, motor skills, and neurologic function. Participants were also evaluated for any psychiatric and autism symptoms. People with a 1q21.1 CNV showed differences in motor and cognitive function as well as differences in head size.

People with a 1q21.1 deletion

People with a 1q21.1 deletion had trouble making particular sounds or processing certain words. They also had trouble with fine motor and overall motor skills. The average verbal and nonverbal IQs for people with the deletion were about the same as the average (90-110) for typical people.

The most common types of psychiatric disorders found were mood and anxiety disorders (26%). The majority of people with a 1q21.1 deletion did not meet the criteria for a diagnosis of autism spectrum disorder. Other medical concerns found in people with the deletion were seizures (18%), hearing loss (17%), low muscle tone (33%), tremors (44%), extreme reflexes (35%), cataracts (33%), and heart problems including differences in heart rhythm and congenital heart defects (33%). Some of the physical features seen were smaller head size (22%) and short height (50%).

Children with a 1q21.1 deletion tend to have:

    • A smaller-than-average head size.
    • Some degree of developmental delay.
      • The most common feature is a fine motor delay or deficit. People with the deletion may, for example, take longer to insert a peg into a pegboard.
      • People with the deletion had trouble understanding and articulating some words.
      • The majority of children with the deletion had some level of cognitive challenge, but most of them did not have intellectual disability.

Few children (2 of 19) with the deletion had a behavioral diagnosis like ADHD or autism.

Importantly, the researchers didn’t notice a distinct pattern of features. That is, the children with a 1q21.1 deletion were very different from one another. Many of the 19 children shared a few features, but they did not share a defined set of medical or behavioral concerns that doctors and parents can expect to see.

Frequency of Medical Concern in People with 1q21.1 Deletion
Medical Concern Percent of People (%)
Short stature 50
Tremors 44
Extreme reflexes 35
Low muscle tone 33
Cataracts 33
Heart defect or arrhythmia 33
Mood and/or anxiety disorder 26
Smaller head size 22
Seizures 18
Hearing loss 17


People with a 1q21.1 duplication

People with 1q21.1 duplication had trouble making particular sounds (38%) or processing certain words. They also had trouble with fine motor and overall motor skills. Most of the verbal and nonverbal IQs were in the low-average range. Some people with a duplication were found to have intellectual disability (20%). The most common behavior diagnoses include autism spectrum disorder (41%) and attention deficit hyperactivity disorder (29%). Other common medical problems were a curved spine (36%), problems with walking and agility (39%), low muscle tone (16%), and stomach ulcers (27%). Some of the physical features seen were larger head size (26%) and short height (27%).

Frequency of Medical Concern in People with 1q21.1 Duplication
Medical Concern Percent of People (%)
Autism Spectrum Disorder 41
Walking (gait) differences 39
Scoliosis 36
Short stature 27
Stomach ulcers 27
Larger head size 26
Intellectual Disability (ID) 20
Low muscle tone 16


What are the differences between the effects of deletions and duplications?

A diagnosis of autism spectrum disorder was more common in people with the duplication than in people with the deletion. The researchers also found that for some traits, the effects of deletion and duplication were “mirrors” of each other.

  • People with duplications had larger head sizes, while people with deletions tended to have smaller head sizes.
  •  The verbal IQs and motor skills of people with duplications seemed to be somewhat different from those of typical people. The IQs and motor skills of people with deletions were more similar to those of typical people.
  • People with the deletion and the duplication shared traits such as borderline cognitive (learning/understanding) abilities, motor impairments, and problems articulating words.

This study suggested that medical evaluations of people with 1q21.1 deletion or duplication should include:

  1. Psychiatric and neurologic evaluations in childhood, adolescence, and adulthood.
  2. Evaluation by a developmental pediatrician at a young age for ASD, intellectual disability, ADHD, and motor difficulties.
  3. Hearing tests as part of well-child visits. A greater proportion of children with a 1q21.1 deletion or duplication have hearing issues than do children without a 1q21.1 CNV.
  4. Tests for heart problems.

Download our 1q21.1 deletions infographic here.

Download our 1q21.1 duplications infographic here.