Information about dup7q11.23 syndrome

Individuals with the genetic condition designated as dup(7)(q11.23), or "dup 7q11.23” carry extra genetic information (known as a duplication) within a tiny portion of chromosome 7.

Each cell of the body has 23 pairs of chromosomes (22 numbered chromosomes and one pair of sex chromosomes) which contain the genetic information, or genome. When egg and sperm cells are formed, the pairs of chromosomes are separated in a process called meiosis, so that each egg or sperm contains only one copy of each chromosome. Errors that occur during this process can result in genomic imbalances such as missing or extra genetic material. These imbalances can cause genetic syndromes that are associated with a wide variety of clinical outcomes.

Many genetic syndromes that were first described on the basis of clinical findings were later found to be caused by genomic imbalances. New high-resolution tests have more recently enabled the discovery of new genomic syndromes. Two distinct conditions result from errors in meiotic recombination involving the long arm of chromosome 7:

Williams-Beuren syndrome (WBS – OMIM #194050 ) is caused by a deletion, or loss of genetic material, on one copy of chromosome 7. This well-known syndrome is associated with mental retardation with severe deficits in visual-spatial reasoning but spared expressive language. Physically, WBS features include growth retardation, infantile hypercalcemia, and heart abnormalities due to a disruption of the Elastin gene located in the WBS critical region of 7q11.23.

For many deletion syndromes there are reciprocal duplication syndromes that occur through the same mechanism. These duplication syndromes have their own distinct clinical features and should not be confused with the deletion syndrome (such as dup 7q11.23 syndrome and Williams-Beuren syndrome).

Duplication of chromosome 7q11.23 is a newly recognized genetic condition with only a few cases reported in the scientific literature. Patients present with variable developmental delay, which is usually most prominent for language delay. In addition, patients may have behavioral abnormalities similar to those seen in patients with autism or autism-spectrum disorders. The physical manifestations of the syndrome reported so far are nonspecific. The atypical facial features observed in these patients might only be recognizable to a geneticist, and birth defects (if present) are typically mild, such as cleft lip and/or palate. Therefore, the first signs of this syndrome could be delayed speech and behavioral features that would prompt a physician to refer the patient for an autism evaluation.

Due to technological advances in cytogenetics, specifically the use of array comparative genomic hybridization (aCGH) for genetic diagnosis, microdeletions and microduplications can be detected efficiently. Hundreds of chromosome segments can be analyzed at one time searching for chromosomal imbalances. We anticipate that many more individuals will be diagnosed with dup 7q11.23 as this testing is performed more widely.

References:

1. Berg JS, Brunetti-Pierri N, Peters SU, Kang SL, et al. Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region. Genetics in Medicine 2007;9(7):427-441.

2. Depienne C, Heron D, Betancur C, Benyahia B, et al. Autism, language delay and mental retardation in a patient with 7q11 duplication. J Med Genet. 2007;44(7):452-8.

3. Kirchhoff M, Bisgaard A-M, Bryndorf T, Gerdes T. MLPA analysis for a panel of syndromes with mental retardation reveals imbalances in 5.8% of patients with mental retardation and dysmorphic features, including duplications of the Sotos syndrome and Williams-Beuren syndrome regions. Eur J Med Genet 2007;50:33-42.

4. Kriek M, White SJ, Szuhai K, Knijnenburg J, et al. Copy number variation in regions flanked (or unflanked) by duplicons among patients with developmental delay and/or congenital malformations: detection of reciprocal and partial Williams-Beuren duplications. Eur J Hum Genet 2006;14:180–189.

5. Somerville MJ, Mervis CB, Young EJ, Seo EJ, et al. Severe expressive-language delay related to duplication of the Williams-Beuren locus. N Engl J Med. 2005 Oct 20;353(16):1694-701.

6. Torniero C, dalla Bernardina B, Novara F, Vetro A, et al. Cortical dysplasia of the left temporal lobe might explain severe expressive-language delay in patients with duplication of the Williams-Beuren locus. Eur J Hum Genet. 2007 Jan;15(1):62-7. Epub 2006 Oct 31.