Tooth agenesis is a rare genetic condition. Although it can appear on its own, it is often associated with other syndromes, appearing with other symptoms. 

Intervention starts early, with the diagnosis process giving the opportunity for planning from below the age of ten. The importance of early diagnosis is emphasised by the potential connection to another syndrome. This factor also contributes to the requirement for a personalised approach to each case, as the presentation of tooth agenesis can differ greatly even between family members.³⁷

This article will go through tooth agenesis in more detail, and cover some syndromes that can present with this as a symptom, as well as potential intervention and diagnostic methods.

Introduction

Tooth agenesis describes a condition where a person’s permanent teeth are missing. This does not include third molars, otherwise known as wisdom teeth⁴ (these are the most commonly absent, even without tooth agenesis).⁷ It is a rare disease recognised by the National Organisation of Rare Disorders.¹ 

Here are some key related definitions:

• Anodontia - absence of all teeth¹
• Hypodontia - usually one to five teeth missing¹
• Oligodontia - usually six or more teeth missing¹

‘Congenitally missing teeth’ is also used.³ By definition, ‘congenital’ means the condition was present from birth.⁵ However, one issue with this term is that the condition is not diagnosable until the patient is around six years of age. Diagnosis usually occurs within the first 10 years of a child’s life.⁶ Furthermore, permanent teeth development still occurs following birth.³

Tooth agenesis is caused by genetic factors.¹ Many genes have been identified to play a role in tooth development, and some have picked out as being affiliated specifically with this condition.² Mutations of these genes may impact tooth development. For example, a mutation in one gene (PAX9) appears to be linked to the absence of molars during development. Important factors required for tooth development are coded for by some of these genes (MSX1 and PAX9).²

It’s also possible for syndromic tooth agenesis to be accompanied by other dental anomalies.⁶ A few examples are listed below:

• Shorter roots⁶
• Delayed tooth formation⁶
• Teeth transposition⁶

Tooth agenesis can be the symptom of another condition. This would be syndromic tooth agenesis. This is most apparent with anodontia.³ However, nonsyndromic tooth agenesis (NSTA) does exist, and in cases presenting with this, tooth agenesis would be the only condition, with any connected syndromes.³ It’s important to identify the cause/type of tooth agenesis that has occurred, and to look into any associated syndromes to aid clinical diagnosis and treatment. There are many conditions associated with tooth agenesis, such as ectodermal dysplasia, Van der Woude syndrome and Down Syndrome.⁶ These will be discussed further in this article.

Ectodermal dysplasia and tooth agenesis

Ectodermal dysplasias (ED) are a group of conditions, of which over 180 types, with a range of different forms of presentation, have been identified. Even for the same type of ED, the symptoms can differ from person to person.⁸ ED is also recognised by the National Organisation of Rare Diseases as a rare genetic disorder.⁹ This condition concerns the embryonic ectoderm, wherein at least two structures developed from it are anomalous. At least one of the anomalies would be involved in the skin appendages (e.g., hair, nails) or, as we are to discuss, the teeth.⁹ This could feature an abnormal teeth appearance, or could be in the form of tooth agenesis.⁹ 

There are different types of ED that can cause tooth agenesis.¹¹ Hypohidrotic ED is one example. It is also called anhidrotic ED. There are three different forms of this condition: X-linked recessive, autosomal recessive and autosomal dominant. Most appear to be X-linked recessive.¹² Along with other symptoms such as hyperhidrosis, hypotrichosis and potentially distinctive facial features, hypohidrotic ED is characterised by hypodontia.¹⁰ As a genetic condition, it can be caused by mutations in the genes EDA, EDAR, EDARADD and WNT10A.¹⁰ The first three are genes used to assist the development of teeth and other parts of the body (e.g. skin and nails). The last one is also required to produce a protein that helps in teeth development.¹⁰ With the WNT10A gene mutated, it is even more likely that an accompanying symptom would be anodontia (absence of all permanent adult teeth).¹⁰

Fried syndrome is another example of an ED causing tooth agenesis. In fact, the absence of teeth is one of the key symptoms that can be checked during diagnosis. This has been identified as an autosomal recessive genetic condition.¹³ To name a few other EDs that cause a form of tooth agenesis:

• Oculodentodigital dysplasia (ODDD) - selective missing teeth¹⁴
• Trichodental syndrome - oligodontia¹⁵
• Witkop syndrome - “congenitally” missing teeth¹⁶
• Johanson-Blizzard syndrome - absent permanent teeth¹⁷

Other syndromes associated with tooth agenesis

Van der Woude Syndrome (VWS)

Van der Woude syndrome is a rare condition caused by mutations in the IRF6 gene. The characteristic symptoms involve the mouth, including cleft lip and/or palate, and depressions on either side of the bottom lip connected to salivary gland drainage.¹⁸ Sometimes one of the symptoms is tooth agenesis.¹⁹

Axenfeld-rieger syndrome

Axenfeld-Rieger’s main symptoms involve the eyes, however, they do also appear on other parts of the body.²⁰ It is caused by the mutations of several genes e.g., FOXC1, PITX2.²¹ The front of the eye is affected: this may be a thin iris, an off-centre pupil, or multiple holes in the iris that make it appear as though the person has more than one pupil. Many times affected patients develop glaucoma. Alongside some distinctive facial features, Axenfeld-Rieger syndrome can cause oligodontia²⁰ (usually 6 or more teeth missing).

Down syndrome (Trisomy 21)

Down syndrome, also known as Trisomy 21, is caused by the presence of an extra chromosome (a third one instead of a pair at position 21), making this a genetic condition.²² There are a range of different symptoms that may present, such as distinctive facial features, respiratory infections and reduced responsiveness to stimuli.²² Regarding orofacial features, patients with Down syndrome have presented with hypodontia or anodontia, forms of tooth agenesis. There are other potential dental symptoms as well, such as microdontia (smaller teeth than normal), and malocclusion (abnormal teeth alignment).^23,24,25

Oral-facial-digital syndrome

Oral-Facial-Digital syndrome (OFDS) is the term used to describe a group of rare conditions that affect a patient’s oral cavity, face and digits (fingers and toes).²⁶ As part of the oral cavity, the teeth may be affected - this may mean a form of tooth agenesis, or even the addition of extra teeth.²⁶ Aside from this, other oral cavity symptoms may include an unusually lobe-shaped tongue, a cleft in the lip, and a cleft palate.²⁶ 

Gorlin syndrome (Naevoid basal cell carcinoma syndrome)

Gorlin syndrome, also known as naevoid basal cell carcinoma syndrome (NBCCS) (or Gorlin-Goltz syndrome), is a rare genetic condition, and one of the most common symptoms is the development of more than one basal skin cell cancer.^27,28 There are a range of other symptoms that may occur, such as benign tumour formation at the ovary or heart, and changes to bone shape.²⁷ Some patients have presented with dental symptoms, such as malocclusions and impacted teeth, and some with tooth agenesis.²⁹ 

Diagnosis and clinical assessment

Diagnosing tooth agenesis occurs via two clinical methods: dental examination and radiographic assessment. It usually occurs within the patient’s first ten years of life.⁶ It may also include examination of the patient’s family history and genetic testing. As there are two types of tooth agenesis (nonsyndromic (NSTA) and syndromic), the physical examination may help identify any other orofacial symptoms present. This can help cancel out the possibility of there being another syndrome associated with the tooth agenesis. The radiographs will help quantify the number of missing permanent teeth, thus making clear whether it is anodontia, hypodontia or oligodontia. It will also help identify any other dental anomalies that may also be present e.g.,³ radiographic assessment may include panoramic radiography, lateral cephalometric, occlusal, periapical radiography, or a cone based computed tomography (CBCT) scan.^30,31,32,34

Early diagnosis is advantageous to help make sure there are no other syndromes associated with the tooth agenesis. For example, if it were Gorlin syndrome, or OFDS, early diagnosis would help allow for quick action for treatment of tumours, and other symptoms on other parts of the body e.g. at the digits and face. Early diagnosis assists future treatment planning.²

Treatment and management

Dental rehabilitation approaches

Dental rehabilitation can use a variety of specialities as a multidisciplinary team. For example, rehabilitation may use:

• Orthodontics³³
• Maxillofacial surgery³³
• Oral surgery³³
• Prosthodontics³³
• Paediatric dentistry³³
• Genetic counsellors²
• Periodontists²
• Medical practitioners²
• General dental practitioners²

Early diagnosis (as early as before age 10 ),⁵ allows for an early start to rehabilitation. Rehabilitation is adapted to many factors specific to the individual, such as a patient’s age and the number of teeth missing.³³

Patients may use a variety of treatments to help with the tooth agenesis. For example, they may use:

• Dental implants to replace the tooth³⁵
• Orthodontic treatment (e.g., braces, for corrective work)³⁵

Long-term follow-up and care considerations

Treatments, for example orthodontic treatment, will require long-term care. Take using braces - this will require well-functioning braces, thorough cleaning and check-ups with the orthodontist. Keeping teeth healthy is also important, as well as careful monitoring to ensure there are no other symptoms present.

Summary

Tooth agenesis may be a rare condition, but its diagnosis is crucial. Along with the differences in presentation from individual to individual (thus requiring personalised treatment), its association to other diseases makes early identification beneficial for early intervention. Following that, regular check-ups on progress regarding tooth treatment helps to keep the rehabilitation process on the right path. We are seeing a development in the type of treatment that may be used to treat tooth agenesis. Gene therapy and regenerative medicine using stem cells and the body’s signalling pathways aim to tackle the issue by focusing on the genes and their altered functions.³⁶