HIVEP2-related intellectual disability is a neurological disorder characterized by moderate to severe developmental delay and intellectual disability and mild physical abnormalities (dysmorphic features). Early symptoms of the condition include weak muscle tone (hypotonia) and delayed development of motor skills, such as sitting, standing, and walking. After learning to walk, many affected individuals continue to have difficulty with this activity; their walking style (gait) is often unbalanced and wide-based. Speech is also delayed, and some people with this condition never learn to talk. Most people with HIVEP2-related intellectual disability also have unusual physical features, such as widely spaced eyes (hypertelorism), a broad nasal bridge, or fingers with tapered ends, although there is no characteristic pattern of such features among affected individuals. Many people with the condition exhibit neurodevelopmental disorders, such as hyperactivity, attention deficit disorder, aggression, anxiety, and autism spectrum disorder, which is a group of developmental disorders characterized by impaired communication and social interaction.

Other features of HIVEP2-related intellectual disability include mild abnormalities in the structure of the brain and an abnormally small brain and head size (microcephaly). Less common health problems include seizures; recurrent ear infections; and eye disorders, such as eyes that do not look in the same direction (strabismus), "lazy eye" (amblyopia), and farsightedness (hyperopia). Some people with HIVEP2-related intellectual disability have gastrointestinal problems, which can include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and constipation.

HIVEP2-related intellectual disability is a rare disorder. At least nine individuals with the condition have been described in the medical literature.

HIVEP2-related intellectual disability is caused by mutations in the HIVEP2 gene. The protein produced from this gene is most abundant in the brain, where it controls the activity (expression) of genes involved in brain growth and development.

Mutations in the HIVEP2 gene are thought to lead to a shortage of functional HIVEP2 protein. It is unclear how these genetic changes result in the features associated with HIVEP2-related intellectual disability, although researchers speculate that a shortage of the HIVEP2 protein alters the expression of several genes involved in brain growth and development. Abnormalities in the growth and development of the brain likely underlie the cognitive problems and other neurological features of HIVEP2-related intellectual disability. It is unclear how HIVEP2 gene mutations contribute to the unusual physical features and health problems that can occur with this condition.

Genetic Testing Information

• Genetic Testing Registry: Intellectual disability, autosomal dominant 43

Genetic and Rare Diseases Information Center

• Intellectual developmental disorder, autosomal dominant 43

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 43; MRD43

Scientific Articles on PubMed

• PubMed

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• Iwashita Y, Fukuchi N, Waki M, Hayashi K, Tahira T. Genome-wide repression of NF-kappaB target genes by transcription factor MIBP1 and its modulation by O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase. J Biol Chem. 2012 Mar 23;287(13):9887-9900. doi: 10.1074/jbc.M111.298521. Epub 2012 Jan 31. Citation on PubMed or Free article on PubMed Central
• Srivastava S, Engels H, Schanze I, Cremer K, Wieland T, Menzel M, Schubach M, Biskup S, Kreiss M, Endele S, Strom TM, Wieczorek D, Zenker M, Gupta S, Cohen J, Zink AM, Naidu S. Loss-of-function variants in HIVEP2 are a cause of intellectual disability. Eur J Hum Genet. 2016 Apr;24(4):556-61. doi: 10.1038/ejhg.2015.151. Epub 2015 Jul 8. Citation on PubMed or Free article on PubMed Central
• Steinfeld H, Cho MT, Retterer K, Person R, Schaefer GB, Danylchuk N, Malik S, Wechsler SB, Wheeler PG, van Gassen KL, Terhal PA, Verhoeven VJ, van Slegtenhorst MA, Monaghan KG, Henderson LB, Chung WK. Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features. Neurogenetics. 2016 Jul;17(3):159-64. doi: 10.1007/s10048-016-0479-z. Epub 2016 Mar 22. Citation on PubMed or Free article on PubMed Central