X-linked intellectual disability, Siderius type

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What is X-linked intellectual disability, Siderius type?

X-linked intellectual disability, Siderius type is a condition characterized by mild to moderate intellectual disability that affects only males. Affected boys often have delayed development of motor skills such as walking, and their speech may be delayed.

Individuals with X-linked intellectual disability, Siderius type frequently also have an opening in the lip (cleft lip) with an opening in the roof of the mouth (cleft palate). A cleft can occur on one or both sides of the upper lip.

Some boys and men with this condition have distinctive facial features, including a long face, a sloping forehead, a broad nasal bridge, a prominent bone in the lower forehead (supraorbital ridge), and outside corners of the eyes that point upward (upslanting palpebral fissures). Affected individuals may also have low-set ears and large hands.

How common is X-linked intellectual disability, Siderius type?

While X-linked intellectual disability of all types and causes is relatively common, with a prevalence of 1 in 600 to 1,000 males, the prevalence of the Siderius type is unknown. Only a few affected families have been described in the scientific literature.

What genes are related to X-linked intellectual disability, Siderius type?

X-linked intellectual disability, Siderius type is caused by mutations in the PHF8 gene. This gene provides instructions for making a protein that is found in the nucleus of cells, particularly in brain cells before and just after birth. The PHF8 protein attaches (binds) to complexes called chromatin to regulate the activity (expression) of other genes. Chromatin is the network of DNA and protein that packages DNA into chromosomes. Binding with the PHF8 protein is part of the process that changes the structure of chromatin (chromatin remodeling) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene expression is regulated; when DNA is tightly packed, gene expression is often lower than when DNA is loosely packed.

Most PHF8 gene mutations lead to an abnormally short protein that gets transported out of the cell's nucleus. Outside of the nucleus, the PHF8 protein cannot interact with chromatin to regulate gene expression. While the exact disease mechanism is unknown, it is likely that a lack of PHF8 protein in the nucleus of brain cells before birth prevents chromatin remodeling, altering the normal expression of genes involved in intellectual function and formation of structures along the midline of the skull. This altered gene expression leads to intellectual disability, cleft lip and palate, and the other features of X-linked intellectual disability, Siderius type.

How do people inherit X-linked intellectual disability, Siderius type?

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of X-linked intellectual disability, Siderius type?

These resources address the diagnosis or management of X-linked intellectual disability, Siderius type, and may include treatment providers.

You might also find information on the diagnosis or management of X-linked intellectual disability, Siderius type, in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about X-linked intellectual disability, Siderius type?

You may find the following resources about X-linked intellectual disability, Siderius type, helpful. These materials are written for the general public.

MedlinePlus - Health information (2 links)
Additional NIH Resources - National Institutes of Health
National Institute of Dental and Craniofacial Research: Cleft Lip and Palate
Educational resources - Information pages (8 links)
Patient support - For patients and families (6 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for X-linked intellectual disability, Siderius type?

MRXSSD
Siderius-Hamel syndrome
Siderius X-linked mental retardation syndrome
syndromic X-linked mental retardation, Siderius type
X-linked mental retardation Hamel type
X-linked mental retardation Siderius type

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about X-linked intellectual disability, Siderius type?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding X-linked intellectual disability, Siderius type?

cell ; chromatin ; chromatin remodeling ; chromosome ; cleft palate ; disability ; DNA ; gene ;gene expression ; inheritance ; inherited ; mental retardation ; motor ; mutation ; nucleus ; palate ;prevalence ; protein ; recessive ; sex chromosomes ; syndrome ; X-linked recessive

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (5 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook