Introduction
Ablepharon macrostomia syndrome is an extremely rare genetic disorder that causes characteristic changes in the appearance of one’s facial features, skin abnormalities and sometimes, physical and intellectual disabilities.1
These symptoms can negatively affect a person’s physical and psychosocial development if not addressed holistically.
Being a genetic condition, this disorder can be diagnosed prenatally especially if the baby is at risk of developing the disorder (for example, if the parent or a close relative has the condition).
Early detection through prenatal diagnosis and genetic counselling is vital to ensure that the family is well prepared to manage the condition effectively and has access to support available in the community. Let us find out about the condition, screening methods and the outlook of the people affected.
Understanding Ablepharon-Macrostomia Syndrome (AMS)
Ablepharon-Macrostomia Syndrome is a genetic disorder, present from birth, with characteristic changes in the baby’s physical appearance. Some of these features can leave the child vulnerable to damage and difficulties in normal physical and social development. Some of the characteristic signs of the condition include:
- Absence of eyelids: defects of the eyelids including absence or abnormality (also known as Ablepharon) is one of the characteristic features of the disease. This can cause the eyes to look protruded, leaving them vulnerable to drying out, injuries or infections
- Macrostomia or widening of the mouth: This is caused due to the widening of the corners of the mouth. This can result in difficulties in feeding babies
- Lack of eyelashes and eyebrows: Another characteristic facial feature in affected children
- Large protruding ears
- Abnormalities in the skin: the skin can look stretched and shiny due to the absence of the fat layer beneath the skin (called subcutaneous fat)
- Underdeveloped nipples and genitals in some cases
- Intellectual difficulties and developmental delays: may occur in affected individuals but are not always present1,2
Why does AMS happen?
Every part of our body appears a certain way because of the genetic code present in our DNA. Rarely, this genetic code or genes can spontaneously change (also called mutations) and result in changes in certain features of the body. Depending on the gene that has mutated, parts of our body can look or function differently. Some mutations are harmless while some can cause significant disability. A gene called the TWIST2 gene, which is responsible for the development of various tissues such as the skin, bones and some organs, has a mutation in AMS.3
The TWIST2 gene affects the formation of the facial features, skin structure and other parts of the body, depending on the severity of the mutation. The exact mechanism of why the mutation occurs is unknown however there are two genetic patterns of occurrence:
- Inherited mutation: the mutation occurs in families. The disease is inherited in an autosomal dominant pattern, which means that the kids have a 50% chance of having the disease.3
- Spontaneous mutations: the mutation occurs spontaneously with no history of the disease occurring in the family.3
Due to the nature of the disease, it is essential for parents to get genetic testing and counselling when there is history of the disease occurring in the family. In cases of spontaneous occurrence, genetic counselling can help navigate the challenges of the disease.
Prenatal diagnosis of AMS
Early detection
Early detection of the disease is crucial to understand the condition, and the potential challenges that come with it and better prepare for interventions to improve quality of life.
Some advantages of early detection are:
- Prenatal diagnosis helps assess the severity of the physical deformities and helps plan to prepare for them. This can include specific medical interventions at birth, making decisions for the delivery and sometimes even considering whether the pregnancy can be continued3
- Early interventions: Knowing that the child will be born with AMS can help proactively prepare for the birth with a holistic care plan involving multiple specialities when required
Methods of prenatal screening
Prenatal screening involves understanding the family history and clinical history as well as invasive and non-invasive methods to detect the genetic abnormality:
- Prenatal ultrasound: the first step as it is the safest during pregnancy. It can detect some facial features such as facial defects. However, there is a chance that abnormalities may not be detected at the first instance unless the sonographer is specifically looking for these signs. This is because the disease is rare4
- Genetic testing: this is a more invasive procedure that involves amniocentesis and chorionic villus sampling. These procedures involve collecting samples of the fluid inside the womb (amniotic fluid) or placental tissue and genetically testing it to confirm the presence of the TWIST2 gene mutation4
Genetic testing is the definitive diagnostic test for AMS. If the mutation is detected and the diagnosis confirmed, specific planning could be made to ensure that the parents and carers are well-equipped to manage the condition. Genetic counselling is essential to parents understand the implications of the disease, carrying the pregnancy and the genetics of the disease.
So what is genetic counselling?
Genetic counselling is an important part of managing AMS. Genetic counsellors provide parents with information about AMS, support available for the complexities of the symptoms, and guidance regarding potential issues. While AMS is quite rare, it is very debilitating and prospective parents must know the implications for the family and make informed decisions about current and future pregnancies.5
For expectant parents especially ones with a history of AMS in the family, genetic counselling can provide valuable insights into the condition. This involves a detailed discussion on the inheritance pattern, the risk of future babies developing the condition and the TWIST2 gene mutation.5
The process of genetic counselling
The first step of genetic counselling is taking a detailed family history and assessing the occurrence of AMS in the family tree. Genetic counsellors obtain the history of any genetic abnormalities, similar conditions and diseases present from birth (congenital conditions). Understanding patterns of inheritance can help in understanding the risk of future babies developing the condition.6
Once the risk is assessed, the next step is prenatal diagnosis. If the tests for AMS are positive, the genetic counsellor will explain the test results to the parents. This explanation will detail the cause of the disease and the potential physical, developmental and social challenges the child may face. A holistic care plan will be made, involving specialists for medical care, counselling for well-being and occupational therapy for developmental challenges in the child.6,7
Psychological support
A diagnosis of AMS can be overwhelming to expectant parents. Genetic counselling offers a safe space to address all issues and concerns regarding their baby. Counsellors are trained to address the psychological aspect of dealing with the genetic disorder with empathy. They offer practical advice to deal with the challenges that come with AMS.7
This support is especially vital when parents are met with the difficult decision of terminating the pregnancy. While the counsellor will not directly make a decision for you, they will provide the space and knowledge required as well as the emotional support needed to make this decision.7
In addition to one-on-one counselling, there are support groups and networks that encourage connections with other families going through a similar process. Genetic counsellors can provide referrals to these relevant services, ensuring a strong support system for families.7
Future family planning
The TWIST2 mutation has a 50% chance of being transferred from parent to child, making it important to plan for future pregnancies wisely. Some newer techniques such as pre-implantation genetic diagnosis with in vitro fertilisation can ensure that the embryo does not contain the gene mutation.6,7
With a proactive family planning approach, individuals can be better aware and prepared for the emotional and financial considerations of having a child with AMS. Families can also consider alternative assisted reproductive technologies or adoption in severe cases. Genetic counsellors are well-equipped to help you make informed decisions about these sensitive issues.6,7
Key takeaways
- Ablepheron Macrostomia Syndrome is a genetic disorder characterised by a characteristic difference in facial features, skin structure, other organs and sometimes, intellectual difficulties
- It is caused by the mutation of the TWIST2 gene which is responsible for the development of skin, bones and other organs
- The features of the disorder include an absence of eyelids, a larger mouth, an absence of subcutaneous fat resulting in a stretched-out appearance, protruding ears and underdeveloped nipples and genitals
- Prenatal diagnosis and genetic counselling are vital to help parents and the individual affected manage this rare yet debilitating condition
- The first diagnostic step is assessing the family tree for the history of genetic disorders
- Prenatal diagnosis is the second step involving an ultrasound to assess facial features and then a diagnostic test for the mutation by performing amniocentesis or chorionic villous sampling
- Genetic counselling is a holistic process that provides the parents with information and support to understand and prepare for the condition
- Genetic counsellors are well equipped to support parents when making difficult decisions regarding pregnancy as well as refer them to support groups for creating a strong social network
FAQs
Why would I be referred to genetic counselling?
You might be referred to genetic counselling if you or your partner have a family history of genetic disorders, if prenatal testing indicates a potential genetic condition in your unborn child, or if you are at higher risk due to factors such as advanced maternal age. Genetic counselling provides critical support and information to help you understand your options and make informed decisions about your pregnancy and family planning.
What to expect when meeting with a genetic counsellor?
When meeting with a genetic counsellor, you can expect a detailed discussion about your family’s medical history, the genetic condition in question, and the potential risks for you and your family. The counsellor will explain any available genetic tests, help you understand the possible outcomes, and provide emotional support. They will also discuss any preventative or management strategies available for the condition being considered.
What questions are asked during genetic counselling?
During genetic counselling, you might be asked about your family’s medical history, including any known genetic disorders. The counsellor may inquire about previous pregnancies, any symptoms you or your family members have experienced, and your understanding of the genetic condition in question. They may also ask about your goals for the counselling session, such as whether you are seeking information for pregnancy planning or for understanding your current health status.
Who is a good candidate for genetic counselling?
Good candidates for genetic counselling include individuals with a personal or family history of genetic disorders, couples who have experienced multiple miscarriages, people from ethnic groups with higher risks for certain genetic conditions, and individuals considering prenatal testing. Anyone concerned about the risk of genetic disorders for themselves or their children may benefit from genetic counselling.
How expensive is genetic testing in the NHS?
In the UK, genetic testing through the NHS is typically provided free of charge when there is a medical need, such as when testing is recommended due to a family history of a genetic condition or based on results from prenatal screenings. However, the availability of certain tests and the criteria for access can vary, and some tests might only be available privately.
Can macrostomia be fixed?
Yes, macrostomia can be surgically corrected. The timing of the surgery often depends on the severity of the condition and the overall health of the child. Surgical intervention aims to restore normal function and improve the cosmetic appearance, allowing for better feeding, speech, and facial symmetry.
How common is macrostomia?
Isolated macrostomia is a rare congenital condition, but when associated with genetic syndromes like Ablepharon-Macrostomia Syndrome, it becomes part of a broader, even rarer condition. The exact prevalence of macrostomia, especially in the context of AMS, is not well documented due to the rarity of the syndrome.
What age can macrostomia be repaired?
Surgical repair of macrostomia is often considered when the child is old enough to tolerate surgery safely, typically between 6 months to 2 years of age. The timing also depends on the severity of the condition and the presence of any associated syndromes that might require early intervention.1
What is the cause of Ablepharon?
Ablepharon-Macrostomia Syndrome is caused by mutations in the TWIST2 gene. This gene plays a crucial role in the development of facial and other bodily structures during embryonic development. Mutations in this gene disrupt normal development, leading to the characteristic features of AMS.
Who discovered Ablepharon-Macrostomia Syndrome?
Ablepharon-Macrostomia Syndrome was first described in the medical literature in the early 1970s by Dr. Rudolf Happle and colleagues. The condition was named based on the primary features of the syndrome: ablepharon (absence or severe reduction of eyelid development) and macrostomia (abnormally large mouth).
References
- Kallish S, McDonald‐McGinn DM, van Haelst MM, Bartlett SP, Katowitz JA, Zackai EH. Ablepharon–Macrostomia syndrome—Extension of the phenotype. American Journal of Medical Genetics Part A. 2011 Dec;155(12):3060-2.
- De Maria B, Mazzanti L, Roche N, Hennekam RC. Barber–Say syndrome and ablepharon–macrostomia syndrome: an overview. American Journal of Medical Genetics Part A. 2016 Aug;170(8):1989-2001.
- Rohena L, Kuehn D, Marchegiani S, Higginson JD. Evidence for autosomal dominant inheritance of ablepharon–macrostomia syndrome. American Journal of Medical Genetics Part A. 2011 Apr;155(4):850-4.
- Carlson LM, Vora NL. Prenatal diagnosis: screening and diagnostic tools. Obstetrics and Gynecology Clinics. 2017 Jun 1;44(2):245-56.
- Milunsky A, Milunsky JM. Genetic counseling: preconception, prenatal, and perinatal. Genetic disorders and the fetus: Diagnosis, prevention, and treatment. 2015 Oct 23:1-67.
- Sheets KB, Crissman BG, Feist CD, Sell SL, Johnson LR, Donahue KC, Masser‐Frye D, Brookshire GS, Carre AM, LaGrave D, Brasington CK. Practice guidelines for communicating a prenatal or postnatal diagnosis of Down syndrome: recommendations of the national society of genetic counselors. Journal of genetic counseling. 2011 Oct;20(5):432-41.
- Metcalfe SA. Genetic counselling, patient education, and informed decision-making in the genomic era. InSeminars in Fetal and Neonatal Medicine 2018 Apr 1 (Vol. 23, No. 2, pp. 142-149). WB Saunders.
