BASICS

DESCRIPTION

• Optic nerve hypoplasia (ONH) is a congenital optic nerve disorder in which the optic nerve is smaller than normal, typically with decreased function.

– May be unilateral or bilateral

– Often associated with other CNS, in particular, midline defects (septo-optic dysplasia [SOD], de Morsier’s syndrome)

EPIDEMIOLOGY

Incidence

SOD: 2–10 per 100,000 births (1,2)

Prevalence

ONH: 6.3 per 100,000 children (3)

RISK FACTORS

• Fetal alcohol syndrome (4)

– Maternal drug use (psychopharmaceutical drugs, some anticonvulsants, quinine LSD, and phencyclidine reported)

– Possibly younger maternal age (5)

– Premature/postmature birth

– Infants of diabetic mothers may have hemihypoplasia of the optic nerve.

(1)C

• Most cases sporadic

– Mutation in HESX1 (3p21.1) identified in SOD, autosomal dominant

– Duplications of SOX3 identified in SOD

– There are numerous ocular (e.g., aniridia) and systemic genetic syndromes (e.g., oculocutaneous albinism) as well as intrauterine infections, which may have ONH as a feature.

GENERAL PREVENTION

• Maternal prenatal care

• Genetic counseling

PATHOPHYSIOLOGY

• Reduced optic nerve fibers

• Poorly understood; possibly related to failed differentiation of retinal ganglion cells or excessive axonal regression during normal optic nerve development

ETIOLOGY

Unknown

COMMONLY ASSOCIATED CONDITIONS (3,5)C

• Decreased visual acuity (ranging to light perception)

• SOD (de Morsier syndrome) (MIM #182230): ONH associated with midline brain defects including absent septum pellucidum, agenesis of corpus callosum, and hypothalamic and pituitary dysfunction. May also have cortical migration defects (e.g., cortical ectopia, pachygyria). Classic de Morsier’s syndrome associated with abnormal facies, macrocrania, and large open anterior fontanelle

• Endocrinopathies including hyperprolactinemia, hypothyroidism, adrenal insufficiency, diabetes insipidus, growth hormone deficiency

DIAGNOSIS

HISTORY

• History of poor visual behavior in one or both eyes since birth with/without nystagmus

– Prenatal history of maternal alcohol/drug use

– Poor infant growth, neonatal jaundice, hypoglycemia, or seizures suggesting pituitary axis dysfunction

PHYSICAL EXAM

• Complete eye exam with indirect ophthalmoscopy to evaluate optic nerve appearance. May have the appearance of the “double ring sign”: a yellow–white ring around the small disc representing the scleral canal that is unfilled due to reduction in optic nerve size

• Increased distance between fovea and temporal optic nerve edge

• May have immature vascular pattern of arcades

• May have foveal hypoplasia

• Nystagmus or strabismus in affected eye(s) may be present.

• May have associated microphthalmia

• Loss of percentiles on growth chart

• May have microcephaly, large anterior fontanel (de Morsier), seizures, developmental delay

• Majority of children, especially with unilateral ONH, will be systemically well, developmentally normal, and with no brain or pituitary involvement.

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Initial lab tests

If abnormal neuroimaging of pituitary or evidence of hormonal signs: thyroid functions (TSH, T3, T4), even if neonatal screen was normal, other serum hormonal screening per endocrinology

Follow-up & special considerations

• Endocrinology evaluation as indicated

• Follow growth charts

Imaging

Initial approach

• MRI of brain and orbits to evaluate intracranial optic nerves and for midline CNS defects (5)[C], cortical migration defects, and pituitary abnormalities including absent pituitary stalk, or ectopic bright spot (displacement of the posterior pituitary up into area of pituitary stalk

• Neuroimaging is an imprecise way of determining optic nerve size or function.

Follow-up & special considerations

Follow development and neurologic signs

Diagnostic Procedures/Other

Referral to endocrinology and neurology as indicated

Pathological Findings

Reduced optic nerve fibers, reduced retinal ganglion cell count, normal outer retinal layers (2)

DIFFERENTIAL DIAGNOSIS

• Optic atrophy

– High hypermetropia

– Tilted optic nerve

– Optic nerve coloboma

– Peripapillary staphyloma/atrophy

TREATMENT

MEDICATION

Hormonal replacement therapy if needed

ADDITIONAL TREATMENT

General Measures

• Amblyopia treatment especially if asymmetric bilateral or unilateral

• Low vision aids and support

– Strabismus correction

– Refractive correction if indicated

– Protective eyewear if unilateral poor vision

Issues for Referral

• Endocrinology referral for pituitary dysfunction

• Neurology referral if neurologic signs

• Developmental assessment

• Genetics consultation

COMPLEMENTARY & ALTERNATIVE THERAPIES

• None

• NOTE: there is currently no scientific evidence to support the use of stem cell treatment for this disorder.

SURGERY/OTHER PROCEDURES

Strabismus or nystagmus surgery as indicated

IN-PATIENT CONSIDERATIONS

Admission Criteria

Admission rarely indicated but sudden death and severe pituitary dysfunction may occur.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

• Ongoing ophthalmologic follow-up for visual evaluation, refractive correction, amblyopia therapy

– Low vision evaluation as indicated

– Endocrinology, neurology, and developmental follow-up

PATIENT EDUCATION

• Focus Families: ONH/SOD Information, Education and Support: http://www.focusfamilies.org/

PROGNOSIS

• Visual prognosis variable depending on optic nerve function.

– Prognosis poorly correlated with optic nerve appearance on physical exam or neuroimaging

COMPLICATIONS

• Potentially significantly decreased visual acuity in affected eye(s)

– Pituitary axis dysfunction

– Neurologic sequelae including seizures and developmental delay

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