Oculocutaneous albinism (OCA) and xeroderma pigmentosum (XP)

Oculocutaneous albinism (OCA) and xeroderma pigmentosum (XP) are autosomal recessive inherited disorders that primarily affect the skin and eyes, resulting in marked sensitivity to ultraviolet (UV) radiation and an increased risk of skin cancer.

Oculocutaneous albinism (OCA) is characterized by a complete or partial absence of melanin pigment in the skin, hair, and eyes due to defective melanin synthesis caused by mutations affecting the conversion of tyrosine to melanin in melanocytes. The condition is lifelong and present from birth.

Xeroderma pigmentosum (XP) is a rare inherited disorder caused by defective DNA repair mechanisms, resulting in an inability to repair DNA damage induced by ultraviolet light. Consequently, affected individuals develop severe photosensitivity, premature skin damage, and a markedly increased risk of skin cancers at an early age.

Individuals with OCA commonly have:

• Markedly increased risk of skin cancers

• Significant visual impairment

Inheritance pattern: Autosomal recessive

Pathophysiology (Brief)

Oculocutaneous albinism

Melanin protects the skin from ultraviolet radiation and is essential for normal retinal development. Melanin deficiency leads to:

Skin effects

• Increased sun sensitivity

• Ultraviolet-induced DNA damage

• Increased risk of skin cancers

Eye effects

• Foveal hypoplasia

• Misrouting of optic nerves

• Reduced visual acuity

• Photophobia

• Nystagmus

Xeroderma pigmentosum

Defective nucleotide excision repair prevents normal repair of ultraviolet-induced DNA damage, resulting in:

• Extreme photosensitivity

• Progressive skin damage

• Early development of premalignant and malignant skin lesions

Signs & Symptoms

Oculocutaneous albinism

Ocular features

• Photophobia (light sensitivity)

• Nystagmus

• Strabismus (crossed eyes)

• Reduced vision or blindness

• Astigmatism

Skin and hair features

• Very light or white hair

• Pale skin

• Loss or marked reduction of skin and hair pigment

• Easy sunburn

• Freckles or sun spots at an early age

Xeroderma pigmentosum

• Freckling in sun-exposed areas during early childhood

• Dry skin (xerosis)

• Changes in skin pigmentation

• Extreme photophobia

• Early actinic damage

• Multiple premalignant and malignant skin lesions if untreated

Diagnostic criteria

Diagnosis is primarily clinical.

Oculocutaneous albinism

Typical hypopigmentation together with one or more of the following:

• Photophobia

• Nystagmus

• Strabismus

• Visual impairment

• Astigmatism

Xeroderma pigmentosum

Typical findings include:

• Severe photosensitivity

• Early freckling on sun-exposed skin

• Dry skin

• Progressive pigmentary skin changes

• Early onset skin cancers or precancerous lesions

Investigations

Diagnosis is usually clinical, although investigations help confirm the diagnosis and detect complications.

Ophthalmic assessment

• Visual acuity testing

• Refraction assessment

• Fundoscopy for foveal hypoplasia

• Optical coherence tomography (OCT)

Dermatological assessment

• Complete skin examination

• Assessment for premalignant lesions

• Skin biopsy of suspicious lesions

Genetic testing (where available)

• Mutation confirmation

• Family counselling

Non-pharmacological treatment

• Provide genetic counselling to affected individuals and their families.

• Counsel parents that these are inherited genetic disorders.

• Avoid excessive exposure to sunlight, especially in patients with xeroderma pigmentosum.

• Wear protective clothing, including long-sleeved shirts, blouses, trousers or long skirts, and wide-brimmed hats.

• Use sun-protective glasses with ultraviolet (UV) filters.

• Avoid outdoor occupations involving prolonged sun exposure.

• Encourage indoor income-generating activities where appropriate.

• Regular dermatology follow-up for early detection and treatment of skin cancers.

• Regular ophthalmology assessment for visual rehabilitation.

• Cryotherapy for early premalignant skin lesions where indicated.

Pharmacological Treatment

• Sunscreen SPF 30 or higher — apply twice daily at 8:00 AM and 12:00 PM

AND

• 5-Fluorouracil (topical) — apply to early lesions as directed

Surgical Treatment

• Excision of lesions where indicated.

• Refer to an oncologist for patients with extensive involvement.

Important Note

Sunscreen lotions and creams contain physical and chemical agents that absorb or scatter ultraviolet (UV) radiation, thereby reducing skin damage caused by sun exposure.

Uses of sunscreen include:

• Albinism and xeroderma pigmentosum to prevent sunburn and reduce the risk of squamous cell carcinoma, basal cell carcinoma, and melanoma.

• Photosensitive skin conditions such as lupus erythematosus and dermatomyositis, where ultraviolet light worsens disease activity.

• Routine use to help prevent photoaging of the skin.

Referral

Refer urgently to higher center if:

• Suspicious skin lesion

• Non-healing ulcer

• Rapidly growing mass

• Pigmented or bleeding lesion

(Suspected skin cancer)

Complications

• Squamous cell carcinoma (commonest)

• Basal cell carcinoma

• Actinic keratosis

• Severe visual disability

• Social stigma and psychological distress

Prevention

Primary prevention is not possible (genetic condition), but complications can be prevented:

• Lifelong sun protection

• Early treatment of precancerous lesions

• Routine skin screening every 6–12 months

• Vision correction early in childhood

• Genetic counseling before marriage/pregnancy