8p23.1 duplication syndrome is a rare genetic disorder

Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

 caused by a duplication

Gene duplication

Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...

 of a region from human chromosome 8. This duplication syndrome has an estimated prevalence of 1 in 64,000 births and is the reciprocal of the 8p23.1 deletion syndrome. The 8p23.1 duplication is associated with a variable phenotype

Phenotype

A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

 including one or more of speech delay

Speech delay

Speech delay, also known as alalia, refers to a delay in the development or use of the mechanisms that produce speech. Speech, as distinct from language, refers to the actual process of making sounds, using such organs and structures as the lungs, vocal cords, mouth, tongue, teeth, etc...

, developmental delay

Developmental disability

Developmental disability is a term used in the United States and Canada to describe lifelong disabilities attributable to mental or physical impairments, manifested prior to age 18. It is not synonymous with "developmental delay" which is often a consequence of a temporary illness or trauma during...

, mild dysmorphism

Dysmorphic feature

Dysmorphic feature is a medical term referring to a difference of body structure that is suggestive of a congenital disorder, genetic syndrome, or birth defect. A dysmorphic feature can be a minor and isolated birth defect...

, with prominent forehead and arched eyebrows, and congenital heart disease

Congenital heart defect

A congenital heart defect is a defect in the structure of the heart and great vessels which is present at birth. Many types of heart defects exist, most of which either obstruct blood flow in the heart or vessels near it, or cause blood to flow through the heart in an abnormal pattern. Other...

 (CHD) .

Syndrome Description

The phenotypic data on 11 patients indicated that cases are not always ascertained for CHD but that CHD was the most common single feature found in 6 out of 11 individuals . Developmental delay and/or learning difficulties were found in 5 out of 11 cases, but one prenatal case was developing normally at 15 months of age (Case 1,). Three other prenatal cases could not yet be reliably assessed. A variable degree of facial dysmorphism was present in 5 out of 11 individuals. Partial toe syndactyly

Syndactyly

Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans.-Classification:...

 has been found in one mother and son diad

Diad

The diad is a structure in the cardiac myocyte located at the sarcomere Z-line. It is composed of a single t-tubule paired with a terminal cisterna of the sarcoplasmic reticulum. The diad plays an important role in excitation-contraction coupling by juxtaposing an inlet for the action potential...

 and adrenal anomalies in two proband

Proband

Proband, or propositus, is a term used most often in medical genetics and other medical fields to denote a particular subject being studied or reported on. On pedigrees, the proband is noted with an arrow and the box or circle shaded accordingly...

s but not in the duplicated mother of one of them. The phenotype is compatible with independent adult life with varying degrees of support.
Duplication of the GATA4

GATA4

Transcription factor GATA-4 is a protein that in humans is encoded by the GATA4 gene.-Interactions:GATA4 has been shown to interact with NKX2-5, TBX5, ZFPM2, Serum response factor and HAND2.HDAC2- External links :...

 transcription factor is believed to underlie the congenital heart disease and other genes, common to the duplication and deletion syndromes, can be regarded as candidates for the 8p23.1 duplication syndrome. These include the SOX7

SOX genes

SOX genes encode a family of transcription factors that bind to the minor groove in DNA, and belong to a super-family of genes characterized by a homologous sequence called the HMG box. This HMG box is a DNA binding domain that is highly conserved throughout eukaryotic species...

 transcription factor for both CHD  and developmental delay and the TNKS

TNKS

Tankyrase-1 is an enzyme that in humans is encoded by the TNKS gene.-Interactions:TNKS has been shown to interact with MCL1, TNKS1BP1, FNBP1 and TERF1.-Further reading:...

 gene for behavioural difficulties. The diaphragmatic hernia

Diaphragmatic hernia

Diaphragmatic hernia is a defect or hole in the diaphragm that allows the abdominal contents to move into the chest cavity. Treatment is usually surgical.The following types of diaphragmatic hernia exist:* Congenital diaphragmatic hernia** Morgagni's hernia...

 found in the 8p23.1 deletion syndrome has not been found in the 8p23.1 duplication syndrome to date.
The duplication may be associated with copy number changes of the adjacent olfactory receptor

Olfactory receptor

Olfactory receptors expressed in the cell membranes of olfactory receptor neurons are responsible for the detection of odor molecules. Activated olfactory receptors are the initial player in a signal transduction cascade which ultimately produces a nerve impulse which is transmitted to the brain...

/defensin

Defensin

Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They have also been reported in plants. They are, and function as, host defense peptides. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. They consist of 18-45 amino...

 repeats (ORDRs) that predispose to the 8p23.1 deletion and duplication syndromes. High total copy numbers of these repeats have been associated with predisposition to psoriasis

Psoriasis

Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

 and low copy number with predisposition to Crohn's disease

Crohn's disease

Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

.

Size of duplication

The duplication includes ~3.75 Mb between the distal and proximal ORDRs at either end of band 8p23.1. The copy number of the adjacent repeats may also be altered. The 8p23.1 duplication syndrome cannot be distinguished using conventional cytogenetics from high level copy number variation of the repeats themselves.

Both de novo cases and families with transmitted duplications from parents of both sex are known. The duplication is believed to arise de novo as a result of non-allelic homologous recombination (NAHR) between the proximal and distal ORDRs. NAHR is also thought to give rise to the reciprocal microdeletion syndrome, the polymorphic inversion between the ORDRs and a variety of other large scale abnormalities involving the short arm of chromosome 8.

Phenotypes

Primary	Secondary	Tertiary
NEUROLOGY Neurology Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...	MENTAL,COGNITIVE FUNCTION, general abnormalities	Mental retardation/developmental delay
VOICE	Voice, general abnormalities	Speech delay Speech delay Speech delay, also known as alalia, refers to a delay in the development or use of the mechanisms that produce speech. Speech, as distinct from language, refers to the actual process of making sounds, using such organs and structures as the lungs, vocal cords, mouth, tongue, teeth, etc...

External links

• DECIPHER database description