HIVEP2-related intellectual disability

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

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.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Most cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual’s parent or in early embryonic development. These cases occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

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

Understanding terms used in the source

These definitions explain medical words used above. A definition is not evidence that another condition is present, and it does not predict how a symptom will develop. Ask the clinician which terms apply to the actual examination or test result.

Recurrent ear infections

Increased susceptibility to ear infections as manifested by recurrent episodes of ear infections.

Gastroesophageal reflux

A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.

Intellectual disability

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Hyperactivity

Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.

Hypertelorism

Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).

Which doctor should you see?

The suggested department for discussing HIVEP2-related intellectual disability is Infectious Diseases, with a general physician / infectious disease specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which exposure or organism is suspected, and what evidence would confirm it?
• Are precautions, vaccination or advice for close contacts relevant to this infection?
• What should happen if symptoms worsen or do not improve as expected?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for HIVEP2-related intellectual disability. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.