Microphthalmia–dermal aplasia–sclerocornea syndrome

Overview

Microphthalmia–dermal aplasia–sclerocornea syndrome, also known as MIDAS syndrome, is a rare congenital disorder that primarily affects the eyes, skin, and sometimes other systems. The acronym MIDAS stands for Microphthalmia (abnormally small eyes), Dermal Aplasia (absence of skin in certain areas), and Sclerocornea (a condition where the normally clear cornea becomes opaque and resembles the white of the eye).

MIDAS syndrome is classified as an X-linked dominant disorder that predominantly affects females. It is typically lethal in males during early embryonic development, which explains why almost all reported cases are female. The condition is usually evident at birth and can vary in severity depending on the extent of the genetic mutation.

Causes

MIDAS syndrome is caused by mutations in the HCCS gene (holocytochrome c-type synthase), located on the X chromosome (Xp22). This gene is involved in mitochondrial function and plays a role in cellular energy production and apoptosis (programmed cell death).

The syndrome follows an X-linked dominant pattern of inheritance. Females with one altered copy of the gene exhibit symptoms of the syndrome, whereas the condition is typically embryonically lethal in males who have only one X chromosome and thus no normal copy of the gene to compensate for the mutation.

In many cases, the mutation occurs de novo (spontaneously), meaning it is not inherited from either parent but arises during the formation of reproductive cells or early embryogenesis.

Symptoms

The clinical presentation of Microphthalmia–dermal aplasia–sclerocornea syndrome includes a range of abnormalities affecting the eyes, skin, and in some instances, other systems. Common features include:

Ocular Abnormalities

• Microphthalmia: Small, underdeveloped eyes that can affect one or both sides

• Sclerocornea: The cornea is opaque and blends with the sclera, impairing vision

• Anophthalmia: Complete absence of one or both eyes in some severe cases

• Other anomalies such as coloboma, cataracts, or iris hypoplasia

Cutaneous Features

• Dermal aplasia: Absence or thinning of skin, typically on the head, neck, or upper body, often following a Blaschkoid distribution (linear patterns along embryonic skin development lines)

• Atrophic or scar-like areas of skin

• Skin pigmentation abnormalities

Other Possible Anomalies

• Facial asymmetry

• Hearing loss (in some cases)

• Minor skeletal anomalies

• Occasional cardiac or renal anomalies

The severity and combination of symptoms vary between individuals, even among those with the same genetic mutation.

Diagnosis

The diagnosis of MIDAS syndrome is based on clinical features and confirmed through genetic testing. Diagnostic steps include:

• Clinical evaluation: Detailed physical examination focusing on skin lesions and eye abnormalities

• Ophthalmologic assessment: To identify microphthalmia, sclerocornea, and other ocular malformations

• Skin biopsy: May reveal absent or atrophic dermis in affected areas

• Genetic testing: Sequencing of the HCCS gene to detect mutations or deletions

• Imaging studies: Orbital ultrasound or MRI may be used to evaluate the structure of the eyes and brain

• Hearing evaluation and systemic workup: To check for associated anomalies

Because it can resemble other syndromes involving eye and skin defects, differential diagnosis may include conditions like Goltz syndrome (focal dermal hypoplasia) or incontinentia pigmenti.

Treatment

There is no cure for MIDAS syndrome, and treatment is supportive, focused on managing the individual symptoms and improving quality of life. A multidisciplinary team approach is recommended. Treatment may include:

• Ophthalmologic management: Regular eye exams, use of corrective lenses, and surgical interventions for severe ocular anomalies such as corneal opacity or cataracts

• Dermatologic care: Wound care and skin grafts for areas of dermal aplasia if they are large or at risk of infection

• Cosmetic and reconstructive surgery: For facial or skin deformities, depending on severity and patient needs

• Hearing aids: If sensorineural hearing loss is present

• Genetic counseling: Essential for affected families to understand the inheritance pattern and recurrence risk

Psychological support and educational interventions may also be needed to support developmental and social outcomes, especially in cases with visual or sensory deficits.

Prognosis

The prognosis for individuals with Microphthalmia–dermal aplasia–sclerocornea syndrome varies depending on the severity of ocular and systemic manifestations. Life expectancy is generally not significantly reduced if there are no major internal organ anomalies.

However, the visual impairment caused by microphthalmia and sclerocornea can be profound and may affect educational and functional development. Early intervention with vision support services can greatly improve outcomes.

With proper medical care and a supportive environment, many individuals with MIDAS syndrome can lead relatively healthy lives. Ongoing research and advancements in genetic testing continue to improve the diagnosis and understanding of this rare condition.