Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH) is a neurological disorder that can also affect many other body systems. This condition primarily affects neurological development, causing intellectual disability, delayed development of speech and motor skills (such as sitting and walking), or autism spectrum disorder, which is a condition that affects communication and social interaction. Some affected individuals have additional neurological features, such as weak muscle tone (hypotonia), behavioral problems, and seizures.

NEDBEH can affect development of many other parts of the body. Some affected individuals have abnormalities of brain structures, such as the tissue that connects the left and right halves of the brain (the corpus callosum), a tissue called white matter, the fluid-filled cavities (ventricles) near the center of the brain, or a structure at the back of the brain known as the cerebellar vermis. Eye abnormalities that can occur include a gap or hole in one of the structures of the eye (coloboma), underdevelopment (hypoplasia) or breakdown (atrophy) of the nerves that carry information from the eyes to the brain (optic nerves), or unusually small eyeballs (microphthalmia). These eye problems can cause vision impairment. Some affected individuals have heart defects, most commonly ventricular septal defect, which is a hole in the muscular wall (septum) that separates the right and left sides of the heart's lower chambers.

Less commonly, other systems are affected in NEDBEH, including the kidneys and inner ear. Problems with the inner ear can lead to hearing impairment (sensorineural hearing loss).

The signs and symptoms in some people with NEDBEH resemble those of another condition known as CHARGE syndrome; however, people with NEDBEH do not have changes in the gene associated with CHARGE syndrome.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

NEDBEH is caused by mutations in a gene called RERE. This gene provides instructions for making a protein that is critical for normal development before birth. It helps control the activity of a number of genes that are important for early development of the brain, eyes, inner ear, heart, and kidneys.

Researchers suspect that RERE gene mutations reduce or eliminate the function of the RERE protein. A shortage of RERE protein function likely alters the activity of several genes involved in development before birth. These changes prevent the normal development of tissues in the brain, eyes, heart, and other organs. Researchers are working to identify which genes are affected and how changes in their activity lead to the signs and symptoms of NEDBEH. It is unknown why some people with NEDBEH have only neurological problems and others also have structural abnormalities. Researchers suspect that the severity of the condition may be related to the location and type of mutation in the RERE gene. Additional genetic factors that have not been identified, including variations in other genes, may also help determine which body systems are affected.

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

NEDBEH is a rare disorder with unknown prevalence. About twenty individuals with this condition have been described in the medical literature.

Which doctor should you see?

The suggested department for discussing Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart is Cardiology, with a cardiologist 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.

• Is the main concern heart structure, rhythm, circulation or another cause?
• Which symptoms should change the timing of follow-up?
• How would a proposed investigation change the care plan?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart. 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.