Diagnosis of otodental syndrome was established using clinical, histopathological and audiometric methodologies. In normal individuals, by the age of 2-3, radiograph images should depict any signs of premolar development. A formal diagnosis of no premolar growth can be done by age 6 in order to check for signs of otodental syndrome. Sensorineural hearing loss can be another measure for proper diagnosis as well as checking for ocular coloboma. The latter is usually noticed at an around birth.

Molecular genetic testing can aid in the diagnosis of the affected individual, which would determine if there are any abnormalities in the FGF3 gene (11q13) or the FADD gene (11q13.3). Additional tests that can help diagnose otodental syndrome are ear infection tests, hearing tests, oral examination, and eye examinations to check for the specific phenotypic associations. Due to the rarity of otodental syndrome, most symptoms are looked at on an individual basis unless multiple symptoms are all apparent at once.

There is potential for differential diagnosis due to similarities in symptoms. Other diseases that share common symptoms are chondroectodermal dysplasia, achondrodysplasia, and osteopetrosis

Since Duane-radial ray syndrome is a genetic disorder, a genetic test would be performed. One test that can be used is the SALL4 sequence analysis that is used to detect if SALL4 is present. If there is no pathogenic variant observed, a deletion/duplication analysis can be ordered following the SALL4 sequence analysis. As an alternative, another genetic test called a multi-gene panel can be ordered to detect SALL4 and any other genes of interest. The methods used for this panel vary depending on the laboratory.

MRI imaging can be used to detect whether the abducens nerve is present.

Currently there are no open research studies for otodental syndrome. Due to the rarity of this disease, current research is very limited.

The most recent research has involved case studies of the affected individuals and/or families, all of which show the specific phenotypic symptoms of otodental syndrome. Investigations on the effects of FGF3 and FADD have also been performed. These studies have shown successes in supporting previous studies that mutations to FGF3 and neighboring genes may cause the associated phenotypic abnormalities. According to recent studies involving zebrafish embryos, there is also support in that the FADD gene contributed to ocular coloboma symptoms as well.

Future research studies are required in order to better grasp the specific relationship between the gene involved and its effect on various tissues and organs such as teeth, eyes, and ear. Little is known and there is still much to be determined.

Acro–dermato–ungual–lacrimal–tooth (ADULT) syndrome is a rare genetic disease. ADULT syndrome is an autosomal dominant form of ectodermal dysplasia, a group of disorders that affects the hair, teeth, nails, sweat glands, and extremities. The syndrome arises from a mutation in the TP63 gene. This disease was previously thought to be a form of ectrodactyly–ectodermal dysplasia–cleft syndrome (EEC), but was classified as a different disease in 1993 by Propping and Zerres.

ADULT syndrome features include ectrodactyly, syndactyly, excessive freckling, lacrimal duct anomalies, dysplastic nails, hypodontia, hypoplastic breasts and nipples, hypotrichosis, hypohidrosis, broad nasal bridge, midfacial hypoplasia, exfoliative dermatitis, and xerosis. The lack of facial clefting and ankyloblepharon are important because they exist in ectrodactyly–ectodermal dysplasia–cleft syndrome (EEC) but not in ADULT syndrome.

X-ray applications on most cases have brought about little outcome in most of the published case reports. As a consequence, a certain number of authors consider acrogeria mainly as a cutaneous affection, but the bone alterations are well described as part of the syndrome.

For patients who show typical alterations of acrogeria and metageria, in a concomitant way, the single term of "Acrometageria" has been proposed, which can refer to the widest spectrum of premature ageing syndromes.

However, this concept is still not generally accepted in the medical literature.As these are extremely rare syndromes, all sharing an aspect of aging skin similar to progeria, they are also called progeroid syndromes, from time to time.

There is currently no specific treatment available for either of these so-called progeroid syndromes. With this in mind, what is most important when making a differential diagnosis with them is based on the prognosis, which appears to be far better in acrogeria.

Hypotrichosis–acro-osteolysis–onychogryphosis–palmoplantar keratoderma–periodontitis syndrome (also known as "HOPP syndrome") is a cutaneous condition characterized by a prominent palmoplantar keratoderma.

Lachiewicz–Sibley syndrome is a rare autosomal dominant disorder characterized by preauricular pits and renal disease. Persons with this disease may have hypoplasic kidneys or proteinuria. This disease was first described in a Caucasian family of British and Irish descent that emigrated to Ohio in the 19th century before settling in Nebraska. Many of the members of this family still live in Nebraska, although the relatives are now scattered throughout the country.

Unlike branchio-oto-renal (BOR) syndrome, Lachiewicz–Sibley syndrome is characterized by only preauricular pitting and renal disease. Persons with BOR syndrome also present with hearing loss, branchial fistulas or cysts, malformed ears, and lacrimal stenosis. Other anomalies in BOR syndrome may include a long narrow face, a deep overbite, and facial paralysis.

It was characterized in 1985.

Tooth and nail syndrome (also known as "Hypodontia with nail dysgenesis," and "Witkop syndrome") is a rare disorder, first described in 1965, characterized by nails that are thin, small, and friable, and which may show koilonychia at birth.

It is associated with "MSX1".

DC is associated with shorter life expectancy, but many live to at least age 60.

Odonto–tricho-ungual–digital–palmar syndrome is an autosomal dominant skin condition with salient clinical features of natal teeth, trichodystrophy, prominent interdigital folds, simian-like hands with transverse palmar creases, and ungual digital dystrophy.

No intervention is usually recommended unless they are causing difficulty to the infant or mother.

However some recommend that they be removed as the tooth can cut or amputate the tip of the tongue.

They should be left in the mouth as long as possible to decrease the likelihood of removing permanent tooth buds with the natal tooth. They should also not be removed if the infant has hypoprothrombinemia. In case of complications when the natal teeth need to be removed, dental radiographs should be obtained whenever possible, and evaluated and followed up with pediatric dentists.

Haim–Munk syndrome (also known as "palmoplantar keratoderma with periodontitis and arachnodactyly and acro-osteolysis") is a cutaneous condition caused by a mutation in the cathepsin C gene. It was named after Dr. Salim Haim and Dr. Munk.

Recent research has used induced pluripotent stem cells to study disease mechanisms in humans, and discovered that the reprogramming of somatic cells restores telomere elongation in dyskeratosis congenita (DKC) cells despite the genetic lesions that affect telomerase. The reprogrammed DKC cells were able to overcome a critical limitation in TERC levels and restored function (telomere maintenance and self-renewal). Therapeutically, methods aimed at increasing TERC expression could prove beneficial in DKC.

Clinical:

Patients often present with a history of fever of unknown origin, muscular weakness, poor development, abnormal dentition, normal serum calcium, phosphorus, and alkaline phosphatase levels. Associated clinical findings also include glaucoma, photosensitivity, heart block, foot deformities, and chronic psoriasiform skin lesions.

Radiological:

Classic radiologic findings were first described by Edward B. Singleton and David Merten in 1973.

Typical radiographic appearances include skeletal demineralization, expanded shafts of the metacarpals and phalanges with widenend medullary cavities, cardiomegaly, and intramural calcification of the proximal aorta with occasional extension into the aortic or mitral valves.

Other commonly seen radiographic findings include shallow acetabular fossa, subluxation of the femoral head, coxa valga, hypoplastic radial epiphysis, soft tissue calcifications between the radius and ulna, constriction of the proximal radial shaft, acro-osteolysis, and equinovarus foot deformities.

Most of the time, natal teeth are not related to a medical condition. However, sometimes they may be associated with:

- Ellis–van Creveld syndrome

- Hallermann–Streiff syndrome

- Pierre Robin syndrome

- Sotos syndrome

Females are affected more than males, and the condition occurs in permanent (adult) teeth more than deciduous (baby teeth or milk teeth).

Unerupted microdonts may require surgical removal to prevent the formation of cysts. Erupted microdonts, peg laterals especially, may cause cosmetic concern. Such teeth may be restored to resemble normal sized teeth, typically with composite build ups or crowns. Orthodontics may be required in severe cases to close gaps between the teeth.

Singleton Merten Syndrome is an autosomal dominate genetic disorder with variable expression with an onset of symptoms during childhood.

Future studies will look further into the relationship of talon cusp and Rubinstein-Taybi syndrome and other oral-facial-digital syndromes. A former study showed a direct correlation in which 45 affected patients with Rubinstein-Taybi syndrome, 92% of these patients had talon cusp. Other researchers are attempting to trace talon cusp to ancestors and comparing dentition to modern humans. Another study done in 2007 examined the dentition of 301 Native American Indian skeletons for the presence or absence of talon cusp. The results showed five skeletons (2 percent) in the population had the trait.

In 2011, only 21 cases of talon cusp have been reported and are in literature. It appears that as of 2014 and 2015, additional research continues in hopes of finding the cause and mechanism of talon cusp. With the majority of cases of talon cusp being unreported, it remains difficult to conduct tests, come up with conclusions, conduct surgery and perform research with small numbers.

While the clinical picture may point towards the diagnosis of the Roussy–Lévy syndrome, the condition can only be confirmed with absolute certainty by carrying out genetic testing in order to identify the underlying mutations.

Treatment is only required if the occlusion or bite of the person is compromised and causing other dental problems. Multiple long-term clinical problems can arise such as occlusal interferences, aesthetic disturbances, loss of pulp vitality, irritation of tongue during mastication and speech, caries and displacement of the affected tooth. Most people with talon cusp will live their normal lives unless the case is severe and causes a cascade of other dental issues that lead to additional health problems. This dental anomaly would not be considered fatal. Generally talon cusps on lower teeth require no treatment, but talon cusps on upper teeth may interfere with the bite mechanics and may need to be removed or reduced.

Small talon cusps that produce no symptoms or complication for a person can remain untreated. However large talon cusps should not.

Some common treatments include:

- Fissure sealing

- Composite resin restoration

- Reduction of cusp

- Pulpotomy

- Root canal (endodontic treatment)

- Extraction

The condition is usually benign, but it can cause mild irritation to soft tissues around the teeth and the tongue, and if large enough, may pose an aesthetic problem. Talon cusps that are too large are filed down with a motorized file, and then endodontic therapy is administered.

In order to prevent any future dental complications, when talon cusp is present due to an early diagnosis it would be best to see a dentist regularly every six months for routine dental checkups, remain under observation, brush and floss properly and undergo regular topical applications of fluoride gel to prevent caries and to promote enamel strength.

The most extensive epidemiological survey on this congenital malformation has been carried out by Dharmasena et al and using English National Hospital Episode Statistics, they calculated the annual incidence of anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus from 1999 to 2011. According to this study the annual incidence of congenital microphthalmia in the United Kingdom was 10.8 (8.2 to 13.5) in 1999 and 10.0 (7.6 to 12.4) in 2011.