15q13.3 microdeletion syndrome

Other Names: Chromosome 15q13.3 deletion syndrome; Microdeletion 15q13.3 syndrome; Chromosome 15q13.3 microdeletion syndrome; 15q13.3 microdeletion

15q13.3 microdeletion syndrome is a genetic disorder caused by a deletion of several genes on chromosome 15. When a syndrome is caused by the deletion of several genes, it is also known as a microdeletion syndrome or a contiguous gene deletion syndrome.

The deletion occurs on the long (q) arm of the chromosome at a position designated q13.3. This chromosomal change increases the risk of intellectual disability, seizures, behavioral problems, and psychiatric disorders. However, some people with a 15q13.3 microdeletion do not appear to have any associated features.

Epidemiology

15q13.3 microdeletion likely occurs in about 1 in 40,000 people in the general population. It appears to be more common in people with intellectual disability, epilepsy, schizophrenia, or autism spectrum disorders.

Cause

Most people with a 15q13.3 microdeletion are missing a sequence of about 2 million DNA building blocks (base pairs), also written as 2 megabases (Mb), at position q13.3 on chromosome 15. The exact size of the deleted region varies, but it typically contains at least six genes. This deletion usually affects one of the two copies of chromosome 15 in each cell.

The signs and symptoms that can result from a 15q13.3 microdeletion are probably related to the loss of one or more genes in this region. However, it is unclear which missing genes contribute to the specific features of the disorder. Because some people with a 15q13.3 microdeletion have no obvious signs or symptoms, researchers believe that other genetic or environmental factors may also be involved.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

15q13.3 microdeletion is inherited in an autosomal dominant pattern, which means one copy of the deleted region on chromosome 15 in each cell is sufficient to increase the risk of intellectual disability and other characteristic features.

In about 75 percent of cases, individuals with 15q13.3 microdeletion inherit the chromosomal change from a parent. In the remaining cases, 15q13.3 microdeletion occurs in people whose parents do not carry the chromosomal change. In these individuals, the deletion occurs most often as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development.

Signs and symptoms

Individuals with 15q13.3 microdeletion syndrome may have very different signs and symptoms from other affected individuals (even within the same family), or no symptoms at all. Features of the condition may include mild to moderate intellectual disabilities, learning delays, or normal intelligence; autism spectrum disorders; epilepsy (recurring seizures); and mental illness (such as [[]]schizophrenia or bipolar disorder). Various dysmorphic (abnormally formed) features have been reported, but there are no consistent physical features among individuals who have the condition.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

30%-79% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Global developmental delay
• Intellectual disability(Mental deficiency)

5%-29% of people have these symptoms

• Abnormality of cardiovascular system morphology
• Attention deficit hyperactivity disorder(Attention deficit)
• Autism
• Bipolar affective disorder(Bipolar disorder)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Downslanted palpebral fissures(Downward slanting of the opening between the eyelids)
• Epicanthus(Eye folds)
• Frontal bossing
• Macrocephaly(Increased size of skull)
• Macrotia(Large ears)
• Melanocytic nevus(Beauty mark)
• Microcephaly(Abnormally small skull)
• Muscular hypotonia(Low or weak muscle tone)
• Prominent nasal tip(Large nasal tip)
• Protruding ear(Prominent ear)
• Schizophrenia
• Seizure
• Short stature(Decreased body height)
• Strabismus(Cross-eyed)

Diagnosis

The 15q13.3 microdeletion is defined as the presence of a common 2.0-Mb deletion at the approximate position of 30.5-32.5 Mb in the reference genome, which includes deletion of 1.5 Mb of unique sequence as well as an additional 500 kb or more of segmental duplications. No single gene within the deletion has been associated with disease findings. Genomic testing methods that determine the copy number of sequences, such as chromosomal microarray (CMA) using oligonucleotide arrays or SNP genotyping arrays, can detect the 15q13.3 microdeletion in a proband.

Genomic testing methods that determine the copy number of sequences can include chromosomal microarray (CMA) or targeted deletion analysis by fluorescence in situ hybridization (FISH) or multiplex ligation dependent probe amplification (MLPA).

Chromosomal microarray (CMA) using oligonucleotide arrays or SNP genotyping arrays can detect the common deletion in a proband. The ability to size the deletion depends on the type of microarray used and the density of probes in the 15q13.3 region.

Targeted deletion analysis. FISH analysis and MLPA may be used to test at-risk relatives of a proband known to have the 15q13.3 microdeletion. Differential Diagnosis The differential diagnosis of the 15q13.3 microdeletion comprises an extensive and broad spectrum of diseases. It includes any cause of developmental delay, schizophrenia, autism spectrum disorders, and epilepsy without additional distinguishing clinical features.

Treatment

Ideally treatment is tailored to the specific needs of the individual. Because of the high incidence of neurodevelopmental disability, referral to a clinical psychologist for neuropsychological and/or developmental assessment for treatment recommendations is suggested.

Medical treatment for persons with cardiac defects, epilepsy, autism spectrum disorders, and schizophrenia should follow standard practice for these disorders, considering the age of the patient and the specific manifestations.

Additional management in healthy adults who have the 15q13.3 microdeletion is not necessary, although their medical care providers may benefit from being alerted to the possible increased risk for late-onset manifestations (e.g., schizophrenia).

NIH genetic and rare disease info

• NIH info on 15q13.3 microdeletion syndrome

15q13.3 microdeletion syndrome is a rare disease.

15q13.3 microdeletion syndrome Resources
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