Albinism

Overview

Definition

Albinism is a group of inherited disorders affecting the production of melanin and resulting in hypopigmentation.

Classification

Albinism is classified according to its clinical phenotype:

• Oculocutaneous albinism (OCA): affects the skin, eyes, and hair (most common type)
• Ocular albinism (OA): only affects the eyes

Epidemiology

• Affects 1 in 17,000 people in the United States (approximately 18,000 people)
• Sex:
  • Both males and females can have OCA.
  • OA only affects males.
• Affects all races

Etiology

Albinism results from inherited genetic mutations.

• OCA: 
  • 8 subtypes
  • Results from mutations in genes responsible for different components of the melanin synthesis pathway
  • Autosomal recessive inheritance pattern
• OA: 
  • 2 subtypes
  • Caused by gene mutations with X-linked inheritance pattern

Pathophysiology and Clinical Presentation

Pathophysiology

• Impaired melanin biosynthesis in melanocytes → absence or ↓ melanin → hypopigmentation of skin, hair, and eyes
• Depending on the OCA type, there may be complete absence of pigmentation or a variable amount of melanin production.
• The number of melanocytes is not reduced.
• Melanin is also important for the development of structures of the eye and the routing of nerve fibers from the retina to the optic chiasm → ↓ vision in albinism

Clinical presentation

The presentation can vary depending on the different genetic subtypes. However, the following are general signs and symptoms:

• OA:
  • ↓ Pigmentation of the iris and retina
  • Visual defects present at birth:
    • ↓ Visual acuity due to foveal hypoplasia
    • Photophobia
    • ↓ Depth perception
    • Lack of normal binocular vision
  • Nystagmus (involuntary movements of the eyes)
  • Strabismus (eyes do not align properly)
• OCA:
  • Ocular issues, as above
  • Hypopigmentation of skin and hair:
    • The degree of hypopigmentation varies.
    • Can range from white to blond/reddish-blonde hair, eyebrows, and eyelashes
  • Photosensitivity:
    • Sunburns
    • Some subtypes develop pigmented nevi and lentigines.

Diagnosis and Management

Diagnosis

• Albinism is a clinical diagnosis.
• Genetic testing is available but is not routinely performed.

Management

There is no currently available cure, and management is mainly supportive.

• Strict protection from the sun:
  • Sunscreen
  • Protective clothing
  • Sunglasses
• Regular skin examination every 6–12 months for early diagnosis and treatment of skin cancer
• Ocular manifestations:
  • Frequent ophthalmologic examinations
  • Treatment of refractive errors with glasses or contacts
  • Surgery to correct strabismus or cataracts, if needed
• Genetic counseling

Complications

Albinism is associated with an increased risk of skin cancer, with squamous cell carcinoma being the most common.

Differential Diagnosis

The following conditions are differential for OA:

• Optic nerve hypoplasia: a congenital condition characterized by underdevelopment of the optic nerve resulting in vision loss in children. Nystagmus is also seen in this condition. Other central nervous system abnormalities often co-exist. Diagnosis made clinically with fundoscopic examination. However, imaging is often obtained to evaluate for other possible defects. Management is aimed at reducing the impact of vision loss on development.
• Inherited retinal dystrophy: encompasses a group of genetic retinal disorders with variable inheritance patterns. Degeneration and loss of the photoreceptors, rods, and cones occurs, which leads to vision loss, night blindness, photosensitivity, and, possibly, color blindness. The diagnosis is made clinically and confirmed with electro-diagnostic testing. There is no cure currently available, and management is challenging and limited.
• Aniridia: a rare congenital ocular disorder that causes abnormal development of the iris. The cornea, lens, fovea, and optic nerve may also be affected. Affected individuals have low visual acuity, photosensitivity, and nystagmus. Most notably, the iris of the eye is partially or completely absent. The condition is diagnosed with an ophthalmologic examination. Management includes vision correction, lubricating drops, and treatment of associated conditions (e.g., cataracts, glaucoma).

The following conditions must be considered in the differential diagnosis for OCA:

• Prader-Willi syndrome and Angelman syndrome: rare neurodevelopmental disorders caused by microdeletions on chromosome 15, which can include the gene for OCA in approximately 1% of cases. Affected children present with the clinical characteristics of OCA in addition to the physical, behavioral, and developmental abnormalities seen in Prader-Willi or Angelman syndromes (e.g., hypotonia, feeding issues, and developmental delay). Genetic testing confirms the diagnosis. Management requires a multidisciplinary team of medical and therapy specialists.
• Hermansky-Pudlak syndrome: a rare autosomal recessive condition characterized by OCA-like findings and platelet abnormalities that result in bleeding problems and easy bruising. Affected patients have light skin, hair, and eyes. Laboratory studies and genetic testing confirm the diagnosis. In addition to measures used in OCA, management also involves platelet transfusions and desmopressin for bleeding.
• Chediak-Higashi syndrome: a rare autosomal recessive condition characterized by impaired lysis of phagocytized bacteria. The syndrome presents with recurrent bacterial infections, OCA-like findings, neurologic dysfunction, and coagulation defects. Affected patients often have fair skin and grey, silvery hair. The diagnosis is made by evaluating the peripheral blood smear for giant granules in neutrophils and genetic testing. Management involves stem cell transplantation, interferon gamma, and antibiotic therapy to prevent infections.