Rare Pediatrics News

Disease Profile

Chromosome Xq duplication

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Duplication Xq; Trisomy Xq; Xq duplication;

Categories

Chromosome Disorders

Summary

Chromosome Xq duplication is a chromosome abnormality that affects many different parts of the body. People with this condition have an extra copy of the genetic material located on the long arm (q) of the X chromosome in each cell. The severity of the condition and the associated signs and symptoms vary based on the size and location of the duplication; the genes involved; and the sex of the affected person. In general, males are typically more severely affected than females and often experience intellectual disability, developmental delay, short stature, abnormalities of the reproductive organs, and distinctive craniofacial features.[1] Many females with this duplication do not have any symptoms or are only affected with short stature; however, some may be just as severely affected as males with the condition.[2][3] Most cases are inherited in an X-linked manner, often from a mother with no signs or symptoms of the condition.[1] Treatment is based on the signs and symptoms present in each person.[4]

Symptoms

The signs and symptoms of a chromosome Xq duplication vary significantly depending on the size of the duplication, the sex of the affected person, and the genes found on the duplicated segment of the chromosome. In general, males with a chromosome Xq duplication are generally more severely affected than females with the duplication. Common features that may be shared by males with this duplication include:[1]

  • Hypotonia
  • Feeding issues as an infant
  • Brain abnormalities
  • Failure to thrive
  • Developmental delay
  • Intellectual disability
  • Speech/language delay and other difficulties with communication
  • Frequent infections
  • Short stature
  • Microcephaly (unusually small head)
  • Craniofacial abnormalities
  • Abnormal development of reproductive organs
  • Dysfunction of the endocrine system
  • Seizures

Many females with this duplication do not have any symptoms or are only affected with short stature. However, some may be just as severely affected as males with the condition.[2][3]

Cause

People with a chromosome Xq duplication have an extra copy of the genetic material located on the long arm (q) of the X chromosome in each cell. The amount of extra genetic material and which genes are duplicated varies in each person depending on the size and location of the duplication.

Scientists suspect that the features seen in people affected by this condition are caused by the duplication and/or disruption of certain genes found on Xq. The consequences of over-expression of many of the genes located in this region are not well understood. However, there are three specific genes that are fairly well characterized. The duplication of a particular gene, MECP2, may be responsible for many of the signs and symptoms found in affected people. An extra copy of the MECP2 gene is often associated with moderate to severe intellectual disability, developmental delay, weak muscle tone in infancy, feeding difficulties, and/or frequent respiratory infections. An extra copy of the PLP1 gene can be associated with brain abnormalities that are often seen in a group of genetic disorders called leukodystrophies (rare diseases that affect the cells of the brain). Duplication of the OPHN1 gene has been reported in people with severe intellectual disability, microcephaly, and usual facial features. Researchers are working to learn more about the other genes on Xq that may contribute to the features seen in people with a chromosome Xq duplication.[1][4]

Diagnosis

There are several different specialized tests that can be used to diagnose a chromosome Xq duplication. These include:[4]

  • Karyotype a karyotype is a laboratory test that produces an image of a person's chromosomes. This test can be used to diagnose large duplications.
  • FISH a laboratory technique that is used to detect and locate a specific DNA sequence on a chromosome. During FISH, a chromosome is exposed to a small DNA sequence called a probe that has a fluorescent molecule attached to it. The probe sequence binds to its corresponding sequence on the chromosome. This test can be used in combination with karyotyping for duplications that are too small to be seen on karyotype, alone. However, FISH is only useful if the person ordering the test suspects there is a duplication of a specific region of Xq since a diagnosis can only be made if the probe binds the duplicated sequence.
  • Array CGH a technology that detects duplications that are too small to be seen on karyotype.

Treatment

Because chromosome Xq duplication affects many different systems of the body, medical management is often provided by a team of doctors and other healthcare professionals. Treatment for this duplication varies based on the signs and symptoms present in each person. For example, parenteral nutrition and/or other dietary interventions may be recommended for infants and young children with feeding difficulties to prevent poor growth and malnutrition. Children with a speech and/or language delay or other problems with communication may be referred for speech and communication therapy. Medications may be prescribed to treat seizures. Children with delayed motor milestones (i.e. walking) may be referred for physical or occupational therapy. Prophylactic antibiotics may be considered in people with frequent infections.[4]

Please speak to your healthcare provider if you have any questions about your personal medical management plan.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • Xq28 duplications is a source of information and support to families and individuals affected by rare chromosome disorders. Click on the link to view information about Xq28 duplications.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Chromosome Xq duplication. Click on the link to view a sample search on this topic.

        References

        1. Cheng SF, Rauen KA, Pinkel D, Albertson DG, Cotter PD. Xq chromosome duplication in males: clinical, cytogenetic and array CGH characterization of a new case and review. Am J Med Genet A. June 2005; 135(3):308-313. https://www.ncbi.nlm.nih.gov/pubmed/15887264.
        2. Armstrong L, McGowan-Jordan J, Brierley K, Allanson JE. De novo dup(X)(q22.3q26) in a girl with evidence that functional disomy of X material is the cause of her abnormal phenotype. Am J Med Genet A. January 2003; 116A(1):71-76. https://www.ncbi.nlm.nih.gov/pubmed/12476455.
        3. Donnelly DE1, Jones J, McNerlan SE, McGrattan P, Humphreys M, McKee S.. Growth retardation, developmental delay and dysmorphic features in a girl with a partial duplication of Xq. Clin Dysmorphol. April 2011; 20(2):82-85. https://www.ncbi.nlm.nih.gov/pubmed/21326093.
        4. Sanlaville D, Schluth-Bolard C, Turleau C. Distal Xq duplication and functional Xq disomy. Orphanet J Rare Dis. February 2009; 4:4. https://www.ncbi.nlm.nih.gov/pubmed/19232094.
        5. X chromosome. Genetics Home Reference. January 2012; https://ghr.nlm.nih.gov/chromosome/X.

        Rare Pediatrics News