Pigmented hairy epidermal nevus syndrome

Overview

Pigmented Hairy Epidermal Nevus Syndrome (PHENS) is a rare neurocutaneous disorder characterized by the presence of epidermal nevi—localized, pigmented, and often hairy skin lesions—alongside a spectrum of systemic abnormalities, particularly involving the nervous system, eyes, and musculoskeletal structures. This syndrome is part of a broader group of disorders known as epidermal nevus syndromes, which are defined by skin lesions and associated extracutaneous anomalies. PHENS typically presents in early childhood, often at birth, and may affect one side of the body more prominently (a condition known as lateralization).

Causes

Pigmented Hairy Epidermal Nevus Syndrome is believed to result from postzygotic somatic mutations during embryonic development. These mutations lead to mosaicism, where some cells carry the genetic change while others do not. Although the exact genetic mutations responsible for PHENS have not been fully elucidated, somatic mutations in genes involved in the RAS/MAPK signaling pathway (such as HRAS and KRAS) have been implicated in related epidermal nevus syndromes.

These mutations affect both ectodermal derivatives (like skin and nervous tissue) and mesodermal structures (such as bones and connective tissue), explaining the wide range of clinical features.

Symptoms

The hallmark feature of PHENS is the presence of a pigmented and often hairy epidermal nevus, which may be accompanied by various systemic abnormalities. Symptoms and signs can vary widely in severity and distribution.

Cutaneous Features:

• Pigmented epidermal nevus: Dark brown to black patches with a verrucous or velvety surface, often unilateral and linear in distribution

• Hypertrichosis: Excessive hair growth over the nevus, giving it a distinctive hairy appearance

• Lesions present at birth: Though they may become more prominent with age

Neurological Features:

• Seizures or epilepsy

• Intellectual disability or developmental delay

• Hypotonia (low muscle tone)

• Structural brain abnormalities seen on imaging (e.g., hemimegalencephaly or cortical dysplasia)

Ophthalmologic Features:

• Coloboma (a defect in the eye structure)

• Strabismus (misalignment of the eyes)

• Optic nerve hypoplasia

• Refractive errors or vision impairment

Musculoskeletal and Other Features:

• Asymmetry of limbs or body structures

• Scoliosis or other spinal abnormalities

• Overgrowth or undergrowth of limbs (hemihypertrophy or hemihypotrophy)

• Dental anomalies or craniofacial dysmorphisms

Diagnosis

Diagnosis of Pigmented Hairy Epidermal Nevus Syndrome is based on clinical examination, imaging studies, and sometimes genetic testing. It is important to differentiate PHENS from other forms of epidermal nevus syndromes and isolated epidermal nevi that lack systemic involvement.

Diagnostic Evaluation Includes:

• Dermatologic assessment: Detailed examination of the nevus, its distribution, and hair growth

• Neurological evaluation: Including developmental screening, EEG for seizures, and MRI of the brain

• Ophthalmologic exam: Slit-lamp and fundus examination to detect colobomas or optic nerve issues

• Skeletal survey or orthopedic assessment: To evaluate bone or limb asymmetry

• Genetic testing: May identify somatic mutations in skin biopsy samples using next-generation sequencing panels

Early diagnosis is critical for monitoring and managing neurological and developmental complications.

Treatment

There is no cure for Pigmented Hairy Epidermal Nevus Syndrome, and treatment is supportive and symptomatic, tailored to the individual’s specific complications and needs. A multidisciplinary team involving dermatologists, neurologists, ophthalmologists, and orthopedic specialists is often required.

Cutaneous Management:

• Topical treatments: Retinoids or keratolytics may reduce scaling and improve texture

• Laser therapy: Pigment-specific or ablative lasers may reduce pigmentation or hair growth

• Surgical excision: May be considered for cosmetic reasons or if the lesion is irritated, though complete removal is often difficult

Neurological and Developmental Care:

• Antiepileptic medications for seizure control

• Physical and occupational therapy to support motor development

• Speech therapy if communication delays are present

• Special education services for cognitive or learning challenges

Ophthalmologic Interventions:

• Glasses or corrective lenses for refractive errors

• Surgical correction for strabismus if indicated

• Regular vision monitoring and early intervention for visual impairment

Orthopedic and Surgical Management:

• Bracing or physical therapy for musculoskeletal abnormalities

• Corrective surgery for significant limb asymmetry or scoliosis

Prognosis

The prognosis for individuals with Pigmented Hairy Epidermal Nevus Syndrome varies depending on the extent and severity of systemic involvement. In cases with mild skin lesions and no major neurological or structural abnormalities, the outlook is generally favorable, and the condition may be managed cosmetically and supportively.

However, when PHENS is associated with significant neurological impairment, seizures, or structural brain anomalies, the long-term outcomes may be more guarded. Developmental progress, seizure control, and vision preservation are key factors in determining the overall prognosis.

With early diagnosis, appropriate interventions, and coordinated care, many individuals with PHENS can achieve improved quality of life and developmental outcomes.