Introduction

Ectodermal dysplasias are a group of genetic disorders that often result in the abnormal development of  hair, sweat glands and other body parts.. Although there isn’t a widespread effective treatment of the condition yet, there are exciting developments in gene and future therapies, which will be discussed in this article.  

What is ectodermal dysplasia?

Overview

Ectodermal dysplasias are a set of conditions caused by a fault during the development of the child before birth, when the embryo develops, which is also called embryogenesis. The type of ectodermal dysplasia can be categorised depending on the parts of the body that are affected, or which genes are faulty that lead to the abnormalities.

The symptoms can vary in severity, ranging from hypohidrosis (being unable to sweat) to alopecia (loss of or lack of hair growth). Even though the disease is not often life-threatening, it can have a huge impact on the quality of life for both the patient and their family. 

Ectodermal dysplasias have an incidence of 7/10,000¹, but it is not clear which subtype is the most common. The earliest record of the condition appears to be in 1792 in a South Asian family, but the term ‘ectodermal dysplasia’ was first mentioned in 1929².

How does it occur?

Because ectodermal dysplasias are a genetic disease, they are present from birth. This means that most patients inherit the disease through X-linked inheritance ³. Every organism contains chromosomes, which are where DNA is carried. Women and men have different chromosomes, where women have XX and men have XY. This means that if a disease is caused by a gene on the X chromosome, the mother can carry the disease but may not suffer from it because she has XX chromosomes, but if she has a son, he will be more likely to get the disease, as he will only have one X chromosome ³. This is the case for ectodermal dysplasia. 

Embryogenesis is a tightly controlled process, but it means that any disruption can lead to developmental delays or abnormal development. The first step of embryo development is when the fertilised egg divides into 3 germ layers, which are just three different layers of cells that grow into different body parts ⁴. The different germ layers are called the mesoderm, endoderm and ectoderm. For example, tissues that grow from the ectoderm include sweat glands, hair follicles and parts of the oral cavity like the jaw and teeth ⁴. These are all tissues that can be affected in patients who have ectodermal dysplasia. 

As mentioned earlier in the article, ectodermal dysplasias can be divided into types depending on what caused the disease. The type 1 condition in people is caused by poor regulation of developmental processes, such as when and where different tissues grow, and the type 2 condition is caused by having growing cells that were unstable ¹. Either way, it means that tissues that grow from the ectoderm have poor or abnormal growth.

Most of the time, ectodermal dysplasia is caused by a deletion or mutation in a gene that stops the gene from acting normally and because this can happen at a really early stage in development, it can lead to a wide range of issues. Some other patients can experience ectodermal dysplasia because of a mutation that happens randomly, which is called a de novo mutation 1. This means that patients with no family history can experience ectodermal dysplasia, and it is hard to predict who. 

What are the symptoms? 

People can have different symptoms of ectodermal dysplasia, but there are some common symptoms that are listed below:

• Hypohydrosis,² which is when the person produces less or no sweat. Even though it might sound great (to adults) to not sweat, sweating is actually a really helpful way to help regulate body temperature and help to keep the body cool. Really young children who have hypohidrosis because of ectodermal dysplasia cannot express their body temperature, which means that it can rise to a dangerous level 
• Reduced or no body hair present,² and some patients experience alopecia (hair loss on the head)
• Orofacial abnormalities such as abnormally shaped teeth, a reduced number of teeth, enamel defects in the teeth, or a cleft palate

One positive is that symptoms of ectodermal dysplasia are non-progressive ¹, which means that they will not get any worse as the person ages. However, if the abnormalities are severe, the esthetics can be upsetting to children and can sadly really impact their self-confidence and the quality of life. 

Diagnosis

Since we are familiar with the symptoms of ectodermal dysplasia, the condition can be identified fairly easily. In times when the mother wants a diagnosis before birth, something called prenatal genetic testing will be done ². This looks at the blood of the mother to see if there are any genetic markers of ectodermal dysplasia.

Gene therapies

The most exciting development for treating inherited diseases is gene therapy, which works by correcting or replacing the faulty gene. Then it is hoped, in theory, that the healthy gene can prevent the disease from occurring.

Because there are different gene mutations that lead to different types of ectodermal dysplasia, sadly, a successful gene therapy for one type may not be effective to help treat another type. 

The type of ectodermal dysplasia that is caused by a mutation in the EDA1 protein is being studied for gene therapy treatment. The EDA1⁵ protein plays an important role in the normal production of sweat glands, teeth and hair. 

The first time a drug is tested in people is called a phase 1 trial, and when adults with ectodermal dysplasia received the genetically EDA1 protein from an IV drip, they thankfully didn’t experience any negative side effects. This means that the drug was allowed to move on into phase 2 trials.⁵ When the drug was given to pregnant mums who were worried their child might have ectodermal dysplasia, the drug was delivered to the unborn child, and the results showed normal formation of sweat glands and tooth germs, which are the type of cells that teeth grow from. This shows that for the drug to be helpful, it has to be given when the child is still developing and has not been born yet. The same team that did this are recruiting for a trial with more participants ⁵. 

When drugs are given to children who haven’t been born yet, they are also called in utero therapies, and because genetic disorders might be experienced as soon as the child is born, they are quite effective. However, as they are given to an unborn child, there are ethical issues,⁶ and it means it is hard to provide and test the effectiveness of the drug.

Future treatments

Another big win to treat ectodermal dysplasia might be regenerative tissue therapy, but it can only be used to treat specific subtypes. These subtypes are called AEC (ankylobelpharon-ectodermal dysplasia cleft lip/palate) or EEC (ectodactyly ectodermal dysplasia cleft lip/palate), and it is because they are caused when the p63 protein doesn’t work properly. The p63 protein helps develop skin cells ⁵, and patients with the disease can have painful skin erosions or recurring corneal lesions. If doctors can grow skin and corneal cells where the protein works, then the faulty cells can be replaced by a transplant. The correct skin and corneal cells are grown from stem cells, which are cells that can grow into any type of cell, like muscle or nerve.

A common symptom of ectodermal dysplasia is abnormal orofacial development, which includes parts of the mouth and jaw and when the child is born, it can lead to poor tooth growth and jaw development. There are new developments being made in dentistry, where dentists can use prosthetics, implants and orthopaedic structures,⁷ which can help normal development. This will also help reduce the physical characteristics of the disease and improve the quality of life for patients. 

Summary 

Ectodermal dysplasia is a range of conditions that can harshly impact the patient and the patient’s family. The range of causes and symptoms makes it hard for a wide treatment plan to be developed, but there are exciting developments in gene therapy that may be able to reduce the disease’s impact straight from birth. Other promising therapies are focused on dental treatments, which can help reduce the impact on quality of life that the disease may have.