Penetrance

Little information is available regarding penetrance of the 1q21.1 recurrent deletion. Similar to several other recurrent deletions (e.g., 16p11.2, 15q13.3), the 1q21.1 recurrent deletion can be inherited from a parent with minimally abnormal or completely normal clinical findings. In addition, several relatives of probands (e.g., sibs, cousins) with the same 1q21.1 deletion have a normal phenotype or only mild manifestations [; ; ; ; ; Authors, personal observation]. This suggests that the 1q21.1 recurrent deletion has reduced penetrance and variable expressivity.

Source: GeneReviews — "1q21.1 Recurrent Deletion"

Diagnostic Criteria

The breakpoints of the distal 1q21.1 recurrent deletion described in this GeneReview are between BP3 and BP4 ; these are sometimes referred to as class I deletions. Because of the variability of the phenotypic features, the diagnosis of the 1q21.1 recurrent deletion is often made following chromosomal microarray analysis (CMA) or through genomic testing, such as exome analysis.

Suggestive Findings

The 1q21.1 recurrent deletion should be considered in probands with the following clinical features:

Source: GeneReviews — "1q21.1 Recurrent Deletion"

Differential Diagnosis

The differential diagnosis of the 1q21.1 recurrent deletion is broad due to the nonspecific, variable spectrum and the presence of relatively common abnormal phenotypes that occur in affected individuals, including developmental delay, learning problems, and neuropsychiatric disorders. All manifestations of the 1q21.1 recurrent deletion can also be seen in individuals with other genomic disorders. Dual molecular diagnoses (i.e., two distinct pathogenic genetic alterations identified at separate loci) have been reported in multiple individuals with the 1q21.1 recurrent deletion and may explain features that are more severe or atypical compared to findings seen in most individuals with the 1q21.1 recurrent deletion .

Source: GeneReviews — "1q21.1 Recurrent Deletion"

Management Guidelines

No clinical practice guidelines for the 1q21.1 recurrent deletion have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with the 1q21.1 recurrent deletion, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis of the 1q21.1 Recurrent Deletion

Source: GeneReviews — "1q21.1 Recurrent Deletion"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "1q21.1 Recurrent Deletion"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 5.

Recommended Surveillance in Individuals with the 1q21 Recurrent Deletion

System/Concern | Evaluation | Frequency

Growth

| Measurement of growth parameters | At each visit

Gastrointestinal

| Monitor for constipation.

Development

| Monitor developmental progress educational needs.

Neurobehavioral/

Psychiatric

| Assessment for anxiety, ADHD, ASD, behavioral problems

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations such as seizures, tremors, tics.

Musculoskeletal

| Physical medicine, OT/PT assessment of mobility, self-help skills

Family/Community

| Assess family need for social work support, care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).

Eyes | Ophthalmology eval | At least annually in childhood, or as clinically indicated

Hearing

| Audiology eval

ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "1q21.1 Recurrent Deletion"