Ablepharon macrostomia syndrome (AMS) is an extremely rare, autosomal dominant genetic disorder characterized by abnormal phenotypic appearances that primarily affect the head and face as well as the skull, skin, fingers and genitals. AMS generally results in abnormal ectoderm-derived structures. The most prominent abnormality is the underdevelopment (microblepharon) or absence of eyelids – signifying the ablepharon aspect of the disease – and a wide, fish-like mouth – macrostomia. Infants presenting with AMS may also have malformations of the abdominal wall and nipples. Children with AMS might also experience issues with learning development, language difficulties and intellectual disabilities. AMS is caused by mutations in the TWIST2 gene, among others. It is closely related to Barber–Say syndrome in terms of phenotypic abnormalities. Signs and symptoms
AMS is generally characterized by abnormal appearances of the skin, eyes, fingers, genitals, head and face. Infants with AMS will have thin, redundantly wrinkled skin and excessive facial creases; wide-set eyes with absent or severely underdeveloped eyelids and down-turned lower eyelids; and a wide, fish-like mouth that may be fused together at the corners. Other appearances of the face and head include: broad nasal bridge, wide, flared nostrils and thick and flared alae nasi (edges of the nostrils).Abnormalities can also be seen in the hands and fingers, as infants with AMS will also have webbed fingers with limited ability to flex and extend the fingers. Infants with AMS will also display small, rudimentary ears that are atypically low-set on the skull. Absence of the zygomatic bone is also possible.
TWIST2 works to prevent the premature maturation of chondrogenic cells and osteoblasts, the cells that will form cartilage and bone respectively. The dominant mutation in TWIST2 leads to the chondrogenic and osteoblastic cells becoming mature prematurely. This then leads to the primary craniofacial deformities seen in AMS patients. Diagnosis
Ablepharon macrostomia syndrome can be diagnosed at birth by identification of characteristic physical findings, clinical evaluation, and specialized imaging techniques such as CT scans. CT scans can confirm the absence of the zygomatic arch and abnormalities in the cranial and mandibular bones. An ophthalmologist can diagnose abnormalities in the eyelids and confirm microblepharon or ablepharon. Teams of specialist will typically work together to confirm diagnosis and assess treatment options. Pediatricians, gastroenterologists, dermatologists, urologists, and other care providers can be expected to aid in the diagnosis and treatment. Treatment
Primary treatment focuses on relief of immediate symptoms such as providing lubrication to the eyes to relieve pain and dryness; antibiotics may also be prescribed to prevent infections and inflammation. Surgical measures can be taken and a plastic surgeon can correct the lack of eyelids through reconstructive surgery. Surgery to correct malformations of the mouth, ears, genitals, fingers, and skin can also be performed as necessary. Macrostomia, the wide, fish-like mouth, can be corrected by a maxillofacial surgeon. The skin can be treated by means of creams to alleviate dryness and coarseness; in certain cases, botulinum toxin and skin grafts were used to improve the overall appearance.