Ablepharon-Macrostomia Syndrome - Causes, Symptoms, and Management.

Introduction:

Ablepharon macrostomia syndrome is an extremely uncommon multiple congenital syndromes that includes macrostomia, abnormal external ears, syndactyly of the hands and feet, skin abnormalities (like dry, coarse skin or redundant folds of skin), no or little hair, genital malformations, and developmental delay (in two-thirds of cases). In addition, the syndrome is characterized by the association of ablepharon, macro malar hypoplasia, nonexistent or hypoplastic nipples, umbilical anomalies, and growth retardation are some additional signs that have been observed. It is a primarily random condition, but there have been reports of a few familial cases showing a large amount of clinical overlap with Fraser syndrome.

What Is Ablepharon-Macrostomia Syndrome?

Ablepharon macrostomia syndrome is a rare genetic disorder seen in people with ablepharon or microblepharon (no eyelids or eyelids that are not fully developed) and macrostomia (wide mouth). The most important things about the syndrome are that it mainly affects the face and skin and rarely affects the viscera or organs inside the body. This is because Ablepharon-Macrostomia syndrome is a group of diseases that exhibit ectodermal dysplasias, characterized by skin, sweat glands, hair, nails, and teeth problems.

It is different from other ectodermal dysplasias because it does not have the same symptoms. Because of this, it is considered a real malformation syndrome. Also, AMS is caused by mutations in the TWIST2 gene. Because it is an autosomal dominant gene, it happens randomly and on its own in its patients. But mutations in TWIST2 cause not only Ablepharon macrostomia syndrome but also Barber-Say syndrome and Setleis syndrome, so it is essential to test it before making any conclusions.

What Are the Causes of Ablepharon-Macrostomia Syndrome?

The strange mutation of the TWIST2 gene is the primary factor that causes Ablepharon-Macrostomia syndrome. However, due to the fact that the symptoms of this disorder manifested themselves on their own, the affected individual does not receive the mutation from both of the parent's copies of the TWIST2 gene. Instead, the mutation is passed down from just one parent in an autosomal dominant pattern. Nevertheless, the mutated gene needs to be inherited from the parent who is dominant for the individual to be affected by the mutation.

This illness is characterized as a dominant genetic disorder because it is passed down from one parent to the child as a non-functional copy of the gene in the dominant parent ( also called the silent carrier of the disease). The risk is equivalent for both males and females. There is a nearly 50 percent chance that the defective gene will be passed on to the kids of each individual who carries it during pregnancy.

What Are the Signs and Symptoms of Ablepharon-Macrostomia Syndrome?

Common Ablepharon-Macrostomia syndrome symptoms include:

• Macrostomia: Wide mouth due to the distance between the oral commissures (the point where the lateral portions of the upper and lower lips' vermilion meet).

• Hypertrophic Malar Bone: Malar prominence underdevelopment of the jugal bone (bone in the skull).

• Delayed Growth: Before and after birth.

• Hypoplastic Nipples: Underdevelopment of the nipples.

• Syndactyly (Webbed Fingers or Toes): Finger or toe webbing or fusion, with or without bone. "Boney" syndactyly is when a radio-ulnar fusion develops.

• Sparse Hair: Reduced density of hair.

• Psychomotor Developmental Delay: Delay of motor or mental milestones in the areas of development of a child, which includes motor skills, cognitive skills, speech and language, social and emotional skills, and cognitive skills.

• Low-set ears with lobes attached.

• Redundant and wrinkled skin.

• Genital abnormalities.

• Incomplete growth of the eyelids, brows, and eyelashes, or their disappearance.

Infants with Ablepharon-Macrostomia syndrome may exhibit other symptoms, including:

• Wide nasal bridge.

• Small chin.

• Low-set ears with lobes attached.

• Flared nasal passages.

• Deficient hearing.

• The long groove between the nose and lips; philtrum

• Alae nasi - thickly flared nasal margins.

• The corners of the lips have a protruding, cheek-pad-like appearance due to the superolateral protrusion of the cheeks.

• No zygomatic arches are present in the skull.

• Absence of silky, downy hair; lanugo.

• Redundant and wrinkled skin.

• A lack of head hair.

• Absent nipples.

• Hernia of the abdomen

• Underdeveloped or atypical structure of the genitalia (cryptorchidism and hypospadias).

• Males have tiny penises, and females have small labia minora.

What Are the Other Conditions That Can Be Associated With Ablepharon-Macrostomia Syndrome?

Because of its multipurpose function in the process of encoding bones and skin cells, the mutation in the TWIST2 gene not only results in the development of Ablepharon-Macrostomia syndrome but also has the potential to result in the development of other medical conditions, including the following:

1. Barber-Say Syndrome: It is a very rare condition that can be described as abnormally excessive hair growth (also known as hypertrichosis), which is then followed by atrophic (papery thin and fragile skin), ectropion (outward turned eyelids), and macrostomia (larger than the regular mouth) (a large mouth). The existence of a different group of symptoms, such as those listed below, differentiates Ablepharon-Macrostomia syndrome.

• The unnaturally rapid expansion of hair.

• Excessive hair.

• Less marked eye findings.

• Hands and genitalia are normal.

2. Setleis Syndrome: Setleis syndrome, sometimes referred to as focal facial dermal dysplasia 3, is a skin disorder that affects the face from birth. Most of the bitemporal cases reported were in children younger than one-year-old (multiple, scar-like, circular depressions on both temples). The severity of the symptoms distinguishes Setleis syndrome from Ablepharon-Macrostomia syndrome and Barber- Say syndrome, which are otherwise indistinguishable from one another. The single distinguishing feature of Setleis syndrome is its similarity to AMS and BSS. For example, suppose you have entropion, an inward folding of the eyelids, not having cheek pads and bitemporal constriction. In that case, the projection will be significantly less severe.

How Is Ablepharon-Macrostomia Syndrome Diagnosed?

Ablepharon-Macrostomia syndrome can be diagnosed early at birth through a clinical evaluation, a family medical history, and a physical exam with samples and tests. However, regular testing makes it hard to tell the difference between Barber-Say syndrome and Ablepharon-Macrostomia syndrome, so molecular genetic testing for mutations in TWIST2 is needed. In addition to the molecular test, the following tests have been done to diagnose cases of Ablepharon-Macrostomia syndrome :

• Computerized Tomography (CT): Scanning can find abnormalities in the bones, such as prominences on the maxilla and mandible or the absence of the zygomatic arch.
• Ophthalmic Examination: Eye exams are done to determine how the eyes develop and how much damage abnormal eyelids are causing.

How Is Ablepharon-Macrostomia Syndrome Treated?

The main focus of the treatment is on the symptoms causing the most trouble. Since AMS directly affects the health of the eyelids, corrective and reconstructive surgery is the best way to treat it. The goal of these surgeries will be to keep and improve vision problems like corneal clouding (opacification), often seen in newborns.

At a later age, more surgeries and medical procedures will be done to improve function and appearance even more. For example, lagophthalmos is one of the most complicated symptoms for people with AMS (inability to close the eyelids). So, to fix ectropion and underdeveloped eyelids, the skin flaps will be moved to the lid area during surgery. Additional surgeries can be done to fix fingers, skin, or ears that hurt. Early treatment with lubricating eye drops or other supportive care may help ease the symptoms of dry eyes. Some of these are:

• Changes to local flaps.

• Procedures for a facelift.

• Lifting the head.

• Injections of Botox.

• Fat grafting.

• Corrective jaw surgery.

• Nasal reconstruction using rib cartilage grafts.

• These procedures are only recommended to some patients, especially young ones, because they could affect how the head and face grow.

1. Genetic Counseling: Genetic counseling will also be suggested for patients and families to learn more about how Ablepharon-Macrostomia syndrome runs in the family and how it is passed down through genes. In addition, psychosocial support has been recommended for overall health care, not just for the patient but also for their guardians and other family members.

2. Psychosocial Support: Psychosocial support is also essential for children with Ablepharon-Macrostomia syndrome as they age and face social pressures and stigmas about the ideal human body. These may have something to do with how the patient looks in general. A team of well-informed healthcare professionals may be given to the patient and their family to help them deal with the medical and psychosocial aspects of the condition.

Conclusion:

Although there is no cure for Ablepharon-Macrostomia syndrome, treatment regimens suggested by experts can improve development, quality of life, and attractiveness. Patients diagnosed with Ablepharon-Macrostomia syndrome have an average life expectancy but cannot achieve a "normal" physical appearance.