Cryptophthalmos is a rare congenital condition where the eyelids fail to develop properly, causing skin to extend from the forehead to the cheek and cover the eye. This results in the absence of an eyelid opening, known as the palpebral fissure. The term cryptophthalmos translates from its Latin roots as “hidden eye.” The condition can affect one or both eyes, and the skin covering can range from a complete sheet of tissue to partial fusion. In all instances, the issue is the malformation of the eyelid structures.
The Underlying Causes of Cryptophthalmos
The origins of cryptophthalmos are primarily genetic, following an autosomal recessive inheritance pattern. This means an individual must inherit a mutated gene from each parent, who are often carriers without showing signs of the disorder. Mutations in the FRAS1, FREM2, and GRIP1 genes are most commonly identified.
These genes produce proteins that form the FRAS/FREM complex. This protein complex is located in the basement membrane, a thin layer anchoring the upper layer of skin to the layers below. During embryonic development, a functional FRAS/FREM complex helps cells adhere to one another, guiding the proper formation of structures like the eyelids.
When mutations prevent the formation of a functional FRAS/FREM complex, the layers of embryonic skin can separate, leading to blistering. This disruption interferes with the normal processes that lead to the separation of the eyelids and formation of the eye socket. The absence of this cellular adhesion process is the foundational reason for the failure of eyelid development.
Classifications and Associated Syndromes
Cryptophthalmos is categorized into three main types based on the extent of the eyelid malformation. Complete cryptophthalmos is the most severe form, where skin runs continuously from the forehead to the cheek without any indication of eyelids, eyebrows, or eyelashes. In these cases, the underlying eye is often malformed, and there is no conjunctival sac, the membrane that lines the inside of the eyelids.
A less severe presentation is incomplete, or partial, cryptophthalmos. In this form, rudimentary eyelids and a small conjunctival sac may be present, but portions of the underdeveloped eyelids are still fused to the eyeball. The third classification, abortive cryptophthalmos, is the mildest form and involves the upper eyelid skin being attached to the cornea, while the lower eyelid is often normally formed.
Cryptophthalmos is a major diagnostic criterion for a wider genetic disorder known as Fraser syndrome. This syndrome is characterized by a specific set of anomalies. Major criteria for diagnosis include:
- Cryptophthalmos
- Syndactyly (webbing or fusion of fingers or toes)
- Genital abnormalities
- Abnormalities of the larynx and urinary tract
Minor criteria can include malformations of the ears and nose, cleft lip or palate, and renal issues like the absence of a kidney.
Diagnosis and Treatment Approaches
Diagnosis can sometimes be made before birth. Prenatal ultrasounds around 18 weeks of gestation may reveal the absence of the palpebral fissure. If other markers associated with Fraser syndrome are also detected, it strengthens the possibility of the diagnosis. After birth, the diagnosis is made through a direct physical examination.
Treatment is surgical and highly individualized, with goals depending on the anatomy and whether a functional eye exists. The surgery is reconstructive and can involve creating functional eyelids, separating the fused skin, and correcting associated anomalies. This intervention is complex and often performed in stages.
If an eye with vision potential is present, the surgical focus is on uncovering the globe and reconstructing eyelids to protect it. In cases where the eyeball is absent or has no potential for vision, the goal shifts to a cosmetic one. This may involve creating a socket that can hold a prosthetic eye, which helps ensure more typical facial development and improve appearance.
Prognosis and Vision Potential
The long-term outlook for an individual with cryptophthalmos is highly variable. It is dependent on the condition of the underlying eye and the severity of other health issues, particularly those associated with Fraser syndrome. The prognosis for life can be affected by serious internal anomalies, such as laryngeal or renal defects, which can be life-threatening.
The potential for vision is entirely contingent on the development of the eyeball. In many cases of complete cryptophthalmos, the eye globe is severely malformed or may not have formed at all (anophthalmia). If there is no viable eye, vision is not possible, and treatment focuses on cosmetic reconstruction.
In instances of incomplete or abortive cryptophthalmos, a partially developed eye may be present. Surgery to separate the eyelids and expose the cornea may restore some level of light perception or even functional vision in rare cases. However, the cornea is often scarred from being covered by skin, which can limit the visual outcome. Any visual potential that exists is often significantly impaired.