Autosomal dominant optic atrophy plus syndrome

What it is

From: Orphanet

A rare neuro-ophthalmological disease associating the typical optic atrophy with other extra-ocular manifestations such as sensorineural deafness, myopathy, chronic progressive external ophthalmoplegia, ataxia and peripheral neuropathy. More rarely, other manifestations have been associated with this condition, such as spastic paraplegia or multiple-sclerosis like illness.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Optic atrophy · Very frequent (99-80%)

Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Progressive visual loss · Very frequent (99-80%)

A reduction of previously attained ability to see.

Abnormal retinal nerve fiber layer morphology · Frequent (79-30%)

A structural abnormality of the retinal nerve fiber layer

Abnormality of visual evoked potentials · Frequent (79-30%)

An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex.

Absent brainstem auditory responses · Frequent (79-30%)

Lack of measurable response to stimulation of auditory evoked potentials.

EMG: impaired neuromuscular transmission · Frequent (79-30%)

An electromyographic finding associated with erratic or absent neuromuscular transmission with erratic, moment-to-moment changes in the shape of the motor unit potential (MUP).

Fatigue · Frequent (79-30%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Limb-girdle muscle weakness · Frequent (79-30%)

Weakness of the limb-girdle muscles (also known as the pelvic and shoulder girdles), that is, lack of strength of the muscles around the shoulders and the pelvis.

Mitochondrial myopathy · Frequent (79-30%)

A type of myopathy associated with mitochondrial disease and characterized by findings on biopsy such as ragged red muscle fibers.

Myopathy · Frequent (79-30%)

A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.

Progressive external ophthalmoplegia · Frequent (79-30%)

Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades.

Sensorineural hearing impairment · Frequent (79-30%)

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

Bilateral ptosis · Frequent (79-30%)

Absent Achilles reflex · Occasional (29-5%)

Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.

Other findings in the same source

From: Orphanet

Additional reported features include Ataxia (Occasional (29-5%)); Constriction of peripheral visual field (Occasional (29-5%)); EMG: chronic denervation signs (Occasional (29-5%)); Motor axonal neuropathy (Occasional (29-5%)); Peripheral neuropathy (Occasional (29-5%)); Pes cavus (Occasional (29-5%)); Sensory neuropathy (Occasional (29-5%)); Spastic paraplegia (Occasional (29-5%)); Temporal optic disc pallor (Occasional (29-5%)); Cardiomyopathy (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adolescent; Adult; Childhood

Inheritance in the source

From: Orphanet

Autosomal dominant

Frequency and the population described

From: Orphanet

Point prevalence: 1-9 / 1 000 000; Europe; Value and class.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal dominant pattern means that one altered copy of a relevant gene can be sufficient for the condition. Some affected people inherit the change; others have a new change without an affected parent. The precise finding, family history and condition determine what this means for relatives.

Which doctor should you see?

The suggested department for discussing Autosomal dominant optic atrophy plus syndrome is Ophthalmology, with a ophthalmologist as the relevant type of clinician. Ophthalmologist; paediatric services for children as appropriate.

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 part of the eye or visual pathway is affected?
• What change in vision requires immediate contact with the eye service?
• What are the aims and alternatives of any proposed eye treatment?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Autosomal dominant optic atrophy plus syndrome. 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.