A combination of clinical findings and laboratory tests are used to diagnose Rabson-Mendenhall Syndrome. Initially, individuals are screened for symptoms and have their blood sugar levels analyzed. The two principle tests used to determine insulin resistance are the fasting plasma glucose test (FPG) and the oral glucose tolerance test (GTT). Results from a patient with severe insulin resistance will show values exceeding healthy ranges (≤99 mg/dL for FPG and ≤139 mg/dL for GTT) by over 50 units. A genetic history is also established to determine risk of recurrence in the family. Based on the combination of these findings, an appropriate diagnosis is made.

Rabson–Mendenhall syndrome is commonly associated with Donohue syndrome, also known as "Leprechaunism". Both diseases are autosomal recessive disorders caused by mutations on chromosome 19. Severe insulin resistance and an irregular enlargement of the genitalia are also overlapping symptoms.

Medical diagnosis is required. Clinical tests can be performed, as well as molecular genetic testing. The available tests include:

Sequence analysis of the entire coding region

- Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) - Sanger Sequencing: Diagnosis, Mutation Confirmation, Pre-symptomatic, Risk Assessment, Screening

- Craniosynostosis: Diagnosis

- Invitae FGFR3-Related Disorders Test: Pre-symptomatic, Diagnosis, Therapeutic management

Mutation scanning of select exons

- Skeletal Dysplasia Panel: Diagnosis, Prognostic

Sequence analysis of select exons

- Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans (SADDAN, FGFR3): Diagnosis, Mutation Confirmation, Risk Assessment

- Severe Achondroplasia, Developmental Delay, Acanthosis Nigricans: Diagnosis, Mutation Confirmation

Deletion/duplication analysis

- Invitae FGFR3-Related Disorders Test: Pre-symptomatic, Diagnosis, Therapeutic management

Life with SADDAN is manageable, although therapy, surgery, and lifelong doctor surveillance may be required.

In terms of diagnosis for this condition, the following methods/tests are available:

- Endoscopic

- CT scan

- Serum endocrine autoantibody screen

- Histologic test

Treatment of manifestations: special hair care products to help manage dry and sparse hair; wigs; artificial nails; emollients to relieve palmoplantar hyperkeratosis.

Beare–Stevenson cutis gyrata syndrome is so rare that a reliable incidence cannot be established as of yet; fewer than 20 patients with the condition have been reported.

The diagnosis of PPS has been made in several ethnic groups, including Caucasian, Japanese, and sub-Saharan African. Males and females are equally likely to suffer from the syndrome. Since the disorder is very rare, its incidence rate is difficult to estimate, but is less than 1 in 10,000.

Lelis syndrome it is a genetic disorder, a rare condition with dermatological and dental findings characterized by the association of ectodermal dysplasia (hypotrichosis and hypohidrosis) with acanthosis nigricans. Other clinical features may include palmoplantar hyperkeratosis, nail dystrophy, intellectual deficit, disturbances of skin pigmentation (perioral and periorbital hyperpigmentation, vitiligo, and perinevic leukoderma) and hypodontia. Transmission is autosomal recessive.

People with ED often have certain cranial-facial features which can be distinctive: frontal bossing is common, longer or more pronounced chins are frequent, broader noses are also very common. In some types of ED, abnormal development of parts of the eye can result in dryness of the eye, cataracts, and vision defects. Professional eye care can help minimize the effects of ED on vision. Similarly, abnormalities in the development of the ear may cause hearing problems. Respiratory infections can be more common because the normal protective secretions of the mouth and nose are not present. Precautions must be taken to limit infections.

The actual incidence of this disease is not known, but only 243 cases have been reported in the scientific literature, suggesting an incidence of on the order of one affected person in ten million people.

Naegeli–Franceschetti–Jadassohn syndrome (NFJS), also known as chromatophore nevus of Naegeli and Naegeli syndrome, is a rare autosomal dominant form of ectodermal dysplasia, characterized by reticular skin pigmentation, diminished function of the sweat glands, the absence of teeth and hyperkeratosis of the palms and soles. One of the most striking features is the absence of fingerprint lines on the fingers.

Naegeli syndrome is similar to dermatopathia pigmentosa reticularis, both of which are caused by a specific defect in the keratin 14 protein.

Modeling EEC syndrome in vitro has been achieved by reprogramming EEC fibroblasts carrying mutations R304W and R204W into induced pluripotent stem cell (iPSC) lines. EEC-iPSC recapitulated defective epidermal and corneal fates. This model further identified PRIMA-1MET, a small compound that was identified as a compound targeting and reactivating p53 mutants based on a cell-based screening for rescuing the apoptotic activity of p53, as efficient to rescue R304W mutation defect. Of interest, similar effect had been observed on keratinocytes derived from the same patients. PRIMA-1MET could become an effective therapeutic tool for EEC patients.

Further genetic research is necessary to identify and rule out other possible loci contributing to EEC syndrome, though it seems certain that disruption of the p63 gene is involved to some extent. In addition, genetic research with an emphasis on genetic syndrome differentiation should prove to be very useful in distinguishing between syndromes that present with very similar clinical findings. There is much debate in current literature regarding clinical markers for syndromic diagnoses. Genetic findings could have great implications in clinical diagnosis and treatment of not only EEC, but also many other related syndromes.

While there is no cure for JBS, treatment and management of specific symptoms and features of the disorder are applied and can often be successful. Variability in the severity of JBS on a case-by-case basis determines the requirements and effectiveness of any treatment selected.

Pancreatic insufficiency and malabsorption can be managed with pancreatic enzyme replacement therapy, such as pancrelipase supplementation and other related methods.

Craniofacial and skeletal deformities may require surgical correction, using techniques including bone grafts and osteotomy procedures. Sensorineural hearing loss can be managed with the use of hearing aids and educational services designated for the hearing impaired.

Special education, specialized counseling methods and occupational therapy designed for those with mental retardation have proven to be effective, for both the patient and their families. This, too, is carefully considered for JBS patients.

There is no specific treatment or cure for individuals affected with this type of syndrome, though some of the abnormal physical features may be surgically correctable.

HED2 is suspected after infancy on the basis of physical features in most affected individuals. GJB6 is the only gene known to be associated with HED2. Targeted mutation analysis for the four most common GJB6 mutations is available on a clinical basis and detects mutations in approximately 100% of affected individuals. Sequence analysis is also available on a clinical basis for those in whom none of the four known mutations is identified.

ANOTHER syndrome consists of alopecia, nail dystrophy, ophthalmic complications, thyroid dysfunction, hypohidrosis, ephelides and enteropathy, and respiratory tract infections. This is an autosomal recessive variant of ectodermal dysplasia.

Acanthosis nigricans should be distinguished from the casal collar appearing in pellagra.

Rabson and Mendenhall described 3 sibling (2 girls, 1 boy) who initially presented with dental and skin abnormalities, abdominal distention, and phallic enlargement. The children demonstrated early dentition, a coarse, senile-appearing , and striking hirsutism. An "adult growth of hair of head" at 5 years of age was pictured in the case of one of the girls. In the older girl the genitalia were large enough at the age of 6 months to permit vaginal examination for diagnosis of a left ovarian tumor which was removed soon afterward. The children were mentally precocious. Prognathism and very thick fingernails as well as acanthosis nigricans were also described. Insulin-resistant diabetes developed, and the patients died during childhood of ketoacidosis and intercurrent infections. At autopsy pineal hyperplasia was found in all three.

Biologically, infants display fasting hypoglycemia, postprandial hyperglycemia and hyperinsulinemia, which progress to permanent hyperglycemia and recurrent diabetic ketoacidosis.

MDM is most common on the Dalmatian island of Mljet (or "Meleda"), thought to be because of a founder effect. It is of autosomal recessive inheritance. It may be caused by a mutation on the "SLURP1" gene, located on chromosome 8.

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.

Acanthosis nigricans is typically diagnosed clinically. A skin biopsy may be needed in unusual cases. If no clear cause is obvious, it may be necessary to search for one. Blood tests, an endoscopy, or X-rays may be required to eliminate the possibility of diabetes or cancer as the cause.

On biopsy, hyperkeratosis, epidermal folding, leukocyte infltration, and melanocyte proliferation may be seen.

The differential diagnosis is quite extensive and includes

- Buschke–Fischer–Brauer disease

- Curth–Macklin ichthyosis

- Gamborg Nielsen syndrome

- Greither disease

- Haber syndrome

- Hereditary punctate palmoplantar keratoderma

- Jadassohn–Lewandowsky syndrome

- Keratosis follicularis spinulosa decalvans

- Keratosis linearis with ichthyosis congenital and sclerosing keratoderma syndrome

- Meleda disease

- Mucosa hyperkeratosis syndrome

- Naegeli–Franceschetti–Jadassohn syndrome

- Naxos disease

- Olmsted syndrome

- Palmoplantar keratoderma and leukokeratosis anogenitalis

- Pandysautonomia

- Papillomatosis of Gougerot and Carteaud

- Papillon–Lefèvre syndrome

- Punctate porokeratotic keratoderma

- Richner–Hanhart syndrome

- Schöpf–Schulz–Passarge syndrome

- Unna Thost disease

- Vohwinkel syndrome

- Wong's dermatomyositis

This not known with certainty but is estimated to be about one per million. It appears to be more common in females than males.

Focal dermal hypoplasia has been associated with PORCN gene mutations on the X chromosome. 90% of the individuals who are affected with the syndrome are female: the commonly accepted, though unconfirmed, explanation for this is that the non-mosaic hemizygous males are not viable.

The differential diagnosis of focal dermal hypoplasia (Goltz) syndrome includes autosomal recessive Setleis syndrome due to TWIST2 gene mutations. It associated with morning glory anomaly, polymicrogyria, incontinentia pigmenti, oculocerebrocutaneous syndrome, Rothmund-Thomson syndrome and microphthalmia with linear skin defects (also known as MLS) syndrome because they are all caused by deletions or point mutations in the HCCS gene.

Anomalies of the hair shaft caused by ectodermal dysplasia should be ruled out. Mutations in the CDH3 gene can also appear in EEM syndrome.

Rosselli–Gulienetti syndrome, also known as Zlotogora–Ogur syndrome and Bowen–Armstrong syndrome, is a type of congenital ectodermal dysplasia syndrome. The syndrome is relatively rare and has only been described in a few cases.