Oliver–McFarlane syndrome

Overview

Oliver–McFarlane syndrome is a rare genetic disorder characterized by a distinctive combination of eye, hair, and hormonal abnormalities. First described by Oliver and McFarlane in 1962, the syndrome primarily affects the retina, pituitary gland, and hair growth patterns. It belongs to a group of disorders known as retinal degenerative diseases and is notable for presenting with trichomegaly (abnormally long eyelashes), retinal degeneration leading to progressive vision loss, and endocrine dysfunction, particularly growth hormone deficiency.

The condition usually presents in early childhood and is progressive in nature, with visual impairment becoming more severe over time. Due to its multisystem involvement, affected individuals often require lifelong management involving ophthalmology, endocrinology, and genetics specialists.

Causes

Oliver–McFarlane syndrome is caused by mutations in the PNPLA6 gene (patatin-like phospholipase domain-containing protein 6). This gene encodes a protein called neuropathy target esterase (NTE), which is involved in lipid metabolism and neural development, including retinal and pituitary function.

• Inheritance pattern: The syndrome follows an autosomal recessive inheritance pattern, meaning both copies of the gene must carry mutations for the disorder to manifest.

• Genetic mutation: Mutations in PNPLA6 impair the normal function of nerve and endocrine cells, leading to progressive degeneration of the retina, abnormal hair growth, and hormonal deficiencies.

Carriers (individuals with one mutated copy of the gene) typically show no symptoms but can pass the gene on to offspring.

Symptoms

Oliver–McFarlane syndrome manifests as a constellation of symptoms affecting the eyes, endocrine system, and hair. The severity and specific combination of symptoms may vary from person to person.

Ocular Symptoms

• Retinal degeneration: Progressive vision loss due to deterioration of photoreceptor cells in the retina.

• Night blindness (nyctalopia): Difficulty seeing in low-light conditions, often one of the earliest signs.

• Peripheral vision loss: Leading to tunnel vision and eventual legal blindness in advanced stages.

• Optic atrophy: Degeneration of the optic nerve may be present in some cases.

Hair Abnormalities

• Trichomegaly: Markedly long and thick eyelashes, often noticeable in infancy or early childhood.

• Thick eyebrows or scalp hair: May also be observed.

Endocrine and Growth Issues

• Growth hormone deficiency: Leading to short stature and delayed growth.

• Delayed puberty: In some individuals, due to pituitary hormone abnormalities.

• Hypopituitarism: Generalized underactivity of the pituitary gland in severe cases, affecting multiple hormones.

Other Possible Features

• Neurological signs: Mild intellectual disability or motor coordination difficulties in some cases.

• Hearing loss: Occasionally reported.

Diagnosis

Diagnosis of Oliver–McFarlane syndrome requires a multidisciplinary evaluation involving clinical, ophthalmologic, endocrinologic, and genetic assessments.

Clinical Evaluation

• History of progressive vision loss and growth delay.

• Physical examination showing trichomegaly and short stature.

Ophthalmologic Tests

• Electroretinography (ERG): To assess retinal function and confirm photoreceptor degeneration.

• Fundoscopy: Visualization of retinal changes consistent with degeneration.

• Visual field testing: To document peripheral vision loss.

Endocrine Assessment

• Serum growth hormone levels: Often decreased.

• Pituitary function tests: Including stimulation tests for other hormones like ACTH, TSH, and gonadotropins.

Genetic Testing

• PNPLA6 gene sequencing: Confirms the diagnosis by identifying pathogenic mutations.

• Carrier testing: Recommended for family members for reproductive planning.

Treatment

There is no cure for Oliver–McFarlane syndrome, and treatment is supportive and aimed at managing individual symptoms and improving quality of life. A multidisciplinary team is essential for long-term care.

Ophthalmologic Management

• Low vision aids: Including magnifiers, special lighting, or electronic visual enhancement devices.

• Mobility training: Orientation and mobility specialists can help children and adults adapt to vision loss.

• Regular eye exams: To monitor progression and manage complications such as cataracts if they arise.

Endocrine Treatment

• Growth hormone replacement therapy: To improve height and development in children with confirmed deficiency.

• Hormone replacement: For other pituitary hormone deficiencies, including thyroid or adrenal hormones.

Supportive Therapies

• Physical therapy: For coordination and strength, especially if motor delays are present.

• Educational support: Special accommodations for visual or developmental delays in school settings.

• Genetic counseling: For families to understand inheritance patterns and future risks.

Prognosis

The prognosis of Oliver–McFarlane syndrome varies depending on the severity of retinal degeneration and endocrine dysfunction. While life expectancy may not be significantly reduced, the quality of life can be affected by progressive vision loss and growth delays.

With early diagnosis and appropriate management including hormonal therapy and visual rehabilitation, many individuals can lead fulfilling lives. Ongoing monitoring and coordinated care from specialists are essential to address emerging complications and provide supportive treatment throughout development and adulthood.