Ablepharon macrostomia syndrome

Overview

Ablepharon macrostomia syndrome (AMS) is an extremely rare congenital disorder characterized by multiple craniofacial, skin, and genital abnormalities. The name of the condition comes from two of its hallmark features: ablepharon (absence or severe underdevelopment of the eyelids) and macrostomia (abnormally large mouth opening). Individuals with AMS may also present with underdeveloped or absent ears, abnormal skin texture, and genital malformations. Despite the extensive physical abnormalities, intelligence is typically normal. AMS is present at birth and may require multiple surgeries and long-term management.

Causes

Ablepharon macrostomia syndrome is caused by mutations in the TWIST2 gene, which plays a role in embryonic development, particularly in the formation of tissues and structures in the head and face. The condition follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene is sufficient to cause the disorder. However, most reported cases have resulted from de novo mutations (new mutations not inherited from either parent).

Symptoms

Individuals with AMS exhibit a wide range of congenital anomalies, especially affecting the face and skin. Common symptoms include:

• Ablepharon: Absence or severe underdevelopment of the eyelids, leading to exposed eyes and risk of damage

• Macrostomia: An unusually wide mouth opening

• Absent or malformed ears (microtia): May affect hearing

• Thin, dry, or wrinkled skin: Particularly on the face and scalp

• Underdeveloped or absent nipples

• Scalp hair anomalies: Sparse or absent hair

• Genital anomalies: Such as underdeveloped external genitalia or ambiguous genitalia

• Facial deformities: Including flattened nose, cleft lip or palate, and malformed facial bones

• Webbed fingers or toes (syndactyly): In some cases

Despite the physical abnormalities, individuals with AMS usually have normal cognitive development.

Diagnosis

Diagnosis of ablepharon macrostomia syndrome is based on the characteristic physical features present at birth and confirmed through genetic testing. Diagnostic steps include:

• Clinical evaluation: Detailed physical examination noting craniofacial, skin, and genital features

• Genetic testing: Identification of a pathogenic mutation in the TWIST2 gene confirms the diagnosis

• Hearing and vision assessments: To detect any sensory impairments due to malformed ears or eyelids

• Imaging studies: CT or MRI may be used to evaluate craniofacial structures

Treatment

Treatment for AMS is symptomatic and typically involves multiple specialties, including plastic surgery, dermatology, ophthalmology, audiology, and urology. Management strategies may include:

• Reconstructive surgery: To correct eyelid absence, macrostomia, ear anomalies, and facial deformities

• Ocular protection: Use of lubricating eye drops or ointments, and surgical procedures to protect exposed eyes

• Skin care: Moisturizers and dermatologic treatments for dry or fragile skin

• Surgical correction of genital anomalies

• Speech therapy and dental care: If oral and facial structures affect speech or feeding

• Psychosocial support: For emotional well-being, especially in adolescence

Prognosis

The prognosis for individuals with ablepharon macrostomia syndrome varies depending on the severity of physical anomalies and access to surgical care. With early and coordinated interventions, many patients achieve significant improvement in function and appearance. Importantly, intelligence is usually not affected, and individuals can lead fulfilling lives. Lifelong monitoring and reconstructive procedures may be needed, and supportive care can help address emotional and social challenges related to appearance.