1q21.1 microdeletion syndrome

Alternate names

Chromosome 1q21.1 microdeletion syndrome; 1q21.1 microdeletion; Monosomy 1q21.1

Definition

1q21.1 microdeletion syndrome is a chromosome abnormality where a segment of genetic material on the long arm (or q arm) of chromosome 1 at position 21.1 is missing (or deleted).

Summary

• This chromosomal change increases the risk of delayed development, intellectual disability, physical abnormalities, and neurological and psychiatric problems.
• However, some people with a 1q21.1 microdeletion do not appear to have any associated features.

The structure of 1q21.1

Epidemiology

1q21.1 microdeletion is a rare chromosomal change; only a few dozen individuals with this deletion have been reported in the medical literature.

Cause

• Most people with a 1q21.1 microdeletion are missing a sequence of about 1.35 million DNA building blocks (base pairs), also written as 1.35 megabases (Mb), in the q21.1 region of chromosome 1.
• However, the exact size of the deleted region varies.
• This deletion affects one of the two copies of chromosome 1 in each cell.
• The signs and symptoms that can result from a 1q21.1 microdeletion are probably related to the loss of several genes in this region.
• Researchers are working to determine which missing genes contribute to the specific features associated with the deletion.
• Because some people with a 1q21.1 microdeletion have no obvious related features, additional genetic or environmental factors are thought to be involved in the development of signs and symptoms.
• Researchers sometimes refer to 1q21.1 microdeletion as the recurrent distal 1.35-Mb deletion to distinguish it from the genetic change that causes thrombocytopenia-absent radius syndrome (TAR syndrome).
• TAR syndrome results from the deletion of a different, smaller DNA segment in the chromosome 1q21.1 region near the area where the 1.35-Mb deletion occurs. The chromosomal change related to TAR syndrome is often called the 200-kb deletion.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• 1q21.1 microdeletion is inherited in an autosomal dominant pattern, which means that missing genetic material from one of the two copies of chromosome 1 in each cell is sufficient to increase the risk of delayed development, intellectual disability, and other signs and symptoms.
• In at least half of cases, individuals with a 1q21.1 microdeletion inherit the chromosomal change from a parent.
• In general, parents who carry a 1q21.1 microdeletion have milder signs and symptoms than their children who inherit the deletion, even though the deletion is the same size.
• About one-quarter of these parents have no associated features.
• A 1q21.1 microdeletion can also occur in people whose parents do not carry the chromosomal change.
• In this situation, the deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) in a parent or in early embryonic development.

Signs and symptoms

• Some people with this deletion have no observable features while others have variable findings that can include a small head (microcephaly), developmental delay (speech and motor delays), mild intellectual disability, distinctive facial features, and eye abnormalities.
• Other findings can include seizures as well as abnormalities of the heart, skeleton, and urinary system.
• Psychiatric and behavioral features can include autism spectrum disorders, anxiety and mood disorders, schizophrenia, attention deficit hyperactivity disorder and sleep disorders.

Clinical presentation

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

• Bulbous nose
• Deeply set eye(Deep set eye)
• Epicanthus(Eye folds)
• Frontal bossing
• Global developmental delay
• High palate(Elevated palate)
• Intellectual disability(Mental deficiency)
• Long philtrum
• Microcephaly(Abnormally small skull)
• Short stature(Decreased body height)
• Wide nasal bridge(Broad nasal bridge)

5%-29% of people have these symptoms

• Abnormal cardiac septum morphology
• Agenesis of corpus callosum
• Ankyloglossia(Tongue tied)
• Anxiety(Excessive, persistent worry and fear)
• Attention deficit hyperactivity disorder(Attention deficit)
• Autism
• Broad hallux phalanx(Broad bone of big toe)
• Broad thumb(Broad thumbs)
• Cataract(Clouding of the lens of the eye)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Cryptorchidism(Undescended testes)

Diagnosis

• The distal 1.35-Mb 1q21.1 recurrent microdeletion can be detected by any number of molecular methods that determine the copy number of sequences within the deleted region, including chromosomal microarray analysis (CMA) using oligonucleotides or polymorphic DNA markers (i.e., SNPs).
• Fluorescence in situ hybridization (FISH) analysis may be used to test relatives of a proband known to have this deletion.

Differential Diagnosis The 22q11.2 microdeletion syndrome is the most common microdeletion syndrome and has several features that overlap with those seen in individuals with the 1q21.1 recurrent microdeletion

Treatment

The following are indicated:

• Routine treatment of ophthalmologic, cardiac, and neurologic findings
• Speech, occupational, and physical therapies, as appropriate
• Specialized learning programs to meet individual needs
• No specific antiepileptic or antipsychotic medications are indicated.

NIH genetic and rare disease info

• NIH info on 1q21.1 microdeletion syndrome

1q21.1 microdeletion syndrome is a rare disease.

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