Oculocerebrocutaneous syndrome

Overview

Oculocerebrocutaneous syndrome (OCCS), also known as Delleman–Oorthuys syndrome, is a rare congenital disorder characterized by malformations affecting the eyes (oculo-), brain (cerebro-), and skin (cutaneous). First described in 1981 by Delleman and Oorthuys, this syndrome presents with a distinct pattern of anomalies including orbital cysts or microphthalmia, cerebral malformations, and focal skin defects, especially on the face and scalp. OCCS occurs sporadically, with no known familial inheritance pattern, and affects both males and females, though a male predominance has been reported.

Because the syndrome involves multiple organ systems derived from embryonic ectoderm, it is considered a neurocutaneous disorder. Clinical presentation is variable, and diagnosis typically occurs during infancy based on physical findings and imaging studies.

Causes

The exact cause of oculocerebrocutaneous syndrome is unknown. It is believed to result from a somatic mutation occurring during early embryonic development, which leads to mosaicism—where only some cells in the body carry the mutation. Possible contributing factors include:

• Somatic mosaic mutation: A postzygotic mutation affecting ectodermal tissues during early embryogenesis.

• No known hereditary pattern: OCCS typically occurs sporadically, and familial recurrence is extremely rare.

No specific gene has yet been definitively associated with OCCS, and genetic testing may not always identify a causative mutation. However, ongoing research in the field of neurocutaneous disorders may eventually elucidate its molecular basis.

Symptoms

Symptoms of oculocerebrocutaneous syndrome vary among individuals but generally involve a combination of ocular, cerebral, and cutaneous abnormalities. The most characteristic features include:

Ocular Abnormalities

• Orbital cysts: Fluid-filled cysts replacing or attached to the eyeball, often unilateral.

• Microphthalmia or anophthalmia: Small or absent eye structures.

• Eyelid colobomas: Gaps or notches in the eyelid, usually the upper lid.

• Conjunctival dermoids or lipodermoids

• Visual impairment: Depending on the severity of ocular defects.

Cerebral Abnormalities

• Intracranial cysts: Often involving the arachnoid or choroid plexus.

• Polymicrogyria or cortical dysplasia: Abnormal brain folding and structure.

• Hydrocephalus: Accumulation of cerebrospinal fluid in the brain, may require surgical intervention.

• Seizures: May occur depending on cortical involvement.

• Developmental delay: Ranging from mild to severe cognitive and motor impairment.

Cutaneous Abnormalities

• Aplasia cutis congenita: Congenital absence of skin, often on the scalp or periorbital region.

• Skin tags or nodules: Particularly in the facial or auricular areas.

• Focal dermal hypoplasia: Areas of thin or underdeveloped skin.

Diagnosis

Diagnosis of oculocerebrocutaneous syndrome is primarily clinical, supported by characteristic physical findings and radiological imaging. Key diagnostic steps include:

• Detailed physical examination: Focuses on detecting ocular, cutaneous, and craniofacial abnormalities.

• Ophthalmologic evaluation: Assesses microphthalmia, orbital cysts, and visual function.

• Neuroimaging: MRI or CT scans to identify brain malformations, cysts, or hydrocephalus.

• Dermatological assessment: Examination of skin lesions, scalp defects, and skin tags.

• Genetic testing: Although no specific gene is currently known, chromosomal microarray or exome sequencing may be done to rule out other syndromes.

Differential diagnoses include Goldenhar syndrome, encephalocraniocutaneous lipomatosis, and other neurocutaneous syndromes.

Treatment

There is no cure for oculocerebrocutaneous syndrome. Management is supportive and tailored to the individual’s specific manifestations. A multidisciplinary team approach is essential and may include ophthalmologists, neurologists, dermatologists, plastic surgeons, and developmental specialists.

Ocular Management

• Surgical removal of orbital cysts: Performed if they interfere with vision or cosmesis.

• Eyelid repair: For eyelid colobomas or dermoids.

• Prosthetic eye placement: In cases of anophthalmia or severe microphthalmia.

Neurological Care

• Management of hydrocephalus: Ventriculoperitoneal shunt placement if needed.

• Anti-seizure medications: For seizure control if present.

• Developmental therapies: Occupational, physical, and speech therapy to support developmental progress.

Dermatological and Reconstructive Care

• Surgical repair of scalp defects: To protect underlying tissues and improve appearance.

• Removal of skin tags or nodules: If symptomatic or for cosmetic purposes.

Prognosis

The prognosis of oculocerebrocutaneous syndrome varies depending on the severity and extent of organ involvement. Children with milder forms of the condition may develop relatively normally with appropriate interventions, while others may experience significant developmental challenges and neurological complications.

Life expectancy is generally not reduced if hydrocephalus and other intracranial complications are properly managed. However, vision loss and developmental delays may persist. Early diagnosis and coordinated care from a multidisciplinary team can significantly improve quality of life and functional outcomes for affected individuals.