The diagnosis of AOS is a clinical diagnosis based on the specific features described above. A system of major and minor criteria was proposed.

The combination of two major criteria would be sufficient for the diagnosis of AOS, while a combination of one major and one minor feature would be suggestive of AOS. Genetic testing can be performed to test for the presence of mutation in one of the known genes, but these so far only account for an estimated 50% of patients with AOS. A definitive diagnosis may therefore not be achieved in all cases.

The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the NEMO IKBKG gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically.

In addition, females with IP have skewed X-chromosome inactivation; testing for this can be used to support the diagnosis.

Many people in the past were misdiagnosed with a second type of IP, formerly known as IP1. This has now been given its own name - 'Hypomelanosis of Ito' (incontinentia pigmenti achromians). This has a slightly different presentation: swirls or streaks of hypopigmentation and depigmentation. It is "not" inherited and does not involve skin stages 1 or 2. Some 33–50% of patients have multisystem involvement — eye, skeletal, and neurological abnormalities. Its chromosomal locus is at Xp11, rather than Xq28.

The overall prognosis is excellent in most cases. Most children with Adams–Oliver syndrome can likely expect to have a normal life span. However, individuals with more severe scalp and cranial defects may experience complications such as hemorrhage and meningitis, leading to long-term disability.

Diagnosis is usually based on clinical findings, although fetal chromosome testing will show trisomy 13. While many of the physical findings are similar to Edwards syndrome there are a few unique traits, such as polydactyly. However, unlike Edwards syndrome and Down syndrome, the quad screen does not provide a reliable means of screening for this disorder. This is due to the variability of the results seen in fetuses with Patau.

Menkes syndrome can be diagnosed by blood tests of the copper and ceruloplasmin levels, skin biopsy, and optical microscopic examination of the hair to view characteristic Menkes abnormalities. X-rays of the skull and skeleton are conducted to look for abnormalities in bone formation. Urine homovanillic acid/vanillylmandelic acid ratio has been proposed as a screening tool to support earlier detection. Since 70% of MNK cases are inherited, genetic testing of the mother can be performed to search for a mutation in the ATP7A gene.

Although LFS is usually suspected when intellectual disability and marfanoid habitus are observed together in a patient, the diagnosis of LFS can be confirmed by the presence of the p.N1007S missense mutation in the "MED12" gene.

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.

In the differential diagnosis of LFS, another disorder that exhibits some features and symptoms of LFS and is also associated with a missense mutation of "MED12" is Opitz-Kaveggia syndrome (FGS). Common features shared by both LFS and FGS include X-linked intellectual disability, hyperactivity, macrocephaly, corpus callosum agenesis and hypotonia. Notable features of FGS that have not been reported with LFS include excessive talkativness, consistent strength in socialization skills, imperforate anus (occlusion of the anus) and ocular hypertelorism (extremely wide-set eyes).

Whereas LFS is associated with missense mutation p.N1007S, FGS is associated with missense mutation p.R961W. As both disorders originate from an identical type of mutation in the same gene, while exhibiting similar, yet distinct characteristics; LFS and FGS are considered to be allelic. In the context of "MED12", this suggests that the phenotype of each disorder is related to the way in which their respective mutations alter the "MED12" sequence and its function.

Many features of gerodermia osteodysplastica (GO) and another autosomal recessive form of cutis laxa, wrinkly skin syndrome (WSS, ""), are similar to such an extent that both disorders were believed to be variable phenotypes of a single disorder.

Several delineating factors, however, suggest that gerodermia osteodysplastica and wrinkly skin syndrome are distinct entities, but share the same clinic spectrum.

While the prevailing feature of wrinkly, loose skin is more localized with GO, it is usually systemic, yet eases in severity with age during the course of WSS. Also, as the fontanelles ("soft spots") are usually normal on the heads of infants with GO, they are often enlarged in WSS infants.

While WSS is associated with mutations of genes on chromosomes 2, 5, 7, 11 and 14; GO has been linked to mutations in the protein GORAB. A serum sialotransferrin type 2 pattern, also observed with WSS, is not present in GO patients.

But perhaps the most notable feature, differentiating GO from WSS and similar cutis laxa disorders, is the age-specific metaphyseal peg sometimes found in GO-affected long bone, near the knee. Not appearing until around age 4–5, then disappearing by physeal closure, this oddity of bone is thought to represent a specific genetic marker unique to GO and its effects on bone development.

Urbach–Wiethe disease is typically diagnosed by its clinical dermatological manifestations, particularly the beaded papules on the eyelids. Doctors can also test the hyaline material with a periodic acid-Schiff (PAS) staining, as the material colors strongly for this stain.

Immunohistochemical skin labeling for antibodies for the ECM1 protein as labeling has been shown to be reduced in the skin of those affected by Urbach–Wiethe disease. Staining with anti-type IV collagen antibodies or anti-type VII collagen antibodies reveals bright, thick bands at the dermoepidermal junction.

Non-contrast CT scans can image calcifications, but this is not typically used as a means of diagnosing the disease. This is partly due to the fact that not all Urbach-Wiethe patients exhibit calcifications, but also because similar lesions can be formed from other diseases such as herpes simplex and encephalitis. The discovery of mutations within the ECM1 gene has allowed the use of genetic testing to confirm initial clinical diagnoses of Urbach–Wiethe disease. It also allows doctors to better distinguish between Urbach–Wiethe disease and other similar diseases not caused by mutations in ECM1.

A diagnosis can be made by an evaluation of medical history and clinical observation. The Beighton criteria are widely used to assess the degree of joint hypermobility. DNA and biochemical studies can help identify affected individuals. Diagnostic tests include collagen gene mutation testing, collagen typing via skin biopsy, echocardiogram, and lysyl hydroxylase or oxidase activity. However, these tests are not able to confirm all cases, especially in instances of an unmapped mutation, so clinical evaluation by a geneticist remains essential. If there are multiple affected individuals in a family, it may be possible to perform prenatal diagnosis using a DNA information technique known as a linkage study. There is poor knowledge about EDS among practitioners.

There does not yet exist a specific treatment for IP. Treatment can only address the individual symptoms.

The original report was of a family in Cardiff, United Kingdom. There are subsequent reports of patients from the USA, France, Australia, UAE, India and from Cuba.

There is no cure for this condition. Treatment is supportive and varies depending on how symptoms present and their severity. Some degree of developmental delay is expected in almost all cases of M-CM, so evaluation for early intervention or special education programs is appropriate. Rare cases have been reported with no discernible delay in academic or school abilities.

Physical therapy and orthopedic bracing can help young children with gross motor development. Occupational therapy or speech therapy may also assist with developmental delays. Attention from an orthopedic surgeon may be required for leg length discrepancy due to hemihyperplasia.

Children with hemihyperplasia are thought to have an elevated risk for certain types of cancers. Recently published management guidelines recommend regular abdominal ultrasounds up to age eight to detect Wilms' tumor. AFP testing to detect liver cancer is not recommended as there have been no reported cases of hepatoblastoma in M-CM patients.

Congenital abnormalities in the brain and progressive brain overgrowth can result in a variety of neurological problems that may require intervention. These include hydrocephalus, cerebellar tonsillar herniation (Chiari I), seizures and syringomyelia. These complications are not usually congenital, they develop over time often presenting complications in late infancy or early childhood, though they can become problems even later. Baseline brain and spinal cord MRI imaging with repeat scans at regular intervals is often prescribed to monitor the changes that result from progressive brain overgrowth.

Assessment of cardiac health with echocardiogram and EKG may be prescribed and arrhythmias or abnormalities may require surgical treatment.

Wiedemann–Rautenstrauch (WR) syndrome , also known as neonatal progeroid syndrome, is an autosomal recessive progeroid syndrome.

WR was first reported by Rautenstrauch and Snigula in 1977; and the earliest reports made subsequently have been by Wiedemann in 1979, by Devos in 1981, and Rudin in 1988. There have been over 30 cases of WR.

WR is associated with abnormalities in bone maturation, and lipids and hormone metabolism. Affected individuals exhibit intrauterine and postnatal growth retardation, leading to short stature and an aged appearance from birth. They have physical abnormalities including a large head (macrocephaly), sparse hair, prominent scalp veins, inward-folded eyelid (entropion), widened anterior fontanelles, hollow cheeks (malar hypoplasia), general loss of fat tissues under the skin (lipoatrophy), delayed tooth eruption, abnormal hair pattern (hypotrichosis), beaked nose, mild to severe mental retardation and dysmorphism.

Marfan lipodystrophy syndrome (MFLS) has sometimes been confused with Wiedemann–Rautenstrauch syndrome, since the Marfanoid features are progressive and sometimes incomplete. MFLS is caused by mutations near the 3'-terminus of "FBN1" that cause a deficiency of the protein hormone asprosin and progeroid-like symptoms with reduced subcutaneous white adipose tissue.

Malouf syndrome (also known as "congestive cardiomyopathy-hypergonadotropic hypogonadism syndrome") is a congenital disorder that causes one or more of the following symptoms: mental retardation, ovarian dysgenesis, congestive cardiomyopathy, broad nasal base, blepharoptosis, and bone abnormalities, and occasionally marfanoid habitus (tall stature with long and thin limbs, little subcutaneous fat, arachnodactyly, joint hyperextension, narrow face, small chin, large testes, and hypotonia).

This disease is named after J. Malouf, who performed a case study on a family suffering from this disease in 1985.

More than 80% of children with Patau syndrome die within the first year of life. Children with the mosaic variation are usually affected to a lesser extent. In a retrospective Canadian study of 174 children with trisomy 13, median survival time was 12.5 days. One and ten year survival was 19.8% and 12.9% respectively.

SCARF syndrome is a rare syndrome characterized by skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, retardation, and facial abnormalities. It shares some features with Lenz-Majewski hyperostotic dwarfism syndrome.

There is no diagnosis as yet for Cutis verticis gyrata (CVH), but it can generally be found out by self, when the person is applying oil to the scalp or getting the hair fully shaven. The ripples are present either in identical form, mostly in the posterior direction, sometimes horizontally also, but it looks more like the ripples of the brain.

There is no clinical diagnosis for CVG as these cases are rarely seen and is often comorbid with other conditions.

It is likely that this syndrome is inherited in an autosomal dominant fashion, however there may be a recessive form with hypotonia and developmental delay.

De Barsy syndrome is a rare autosomal recessive genetic disorder. Symptoms include cutis laxa (loose hanging skin) as well as other eye, musculoskeletal, and neurological abnormalities. It is usually progressive, manifesting side effects that can include clouded corneas, cataracts, short stature, dystonia, or progeria (premature aging).

It was first described in 1967 by De Barsy et al. and, as of 2011, there have been 27 cases reported worldwide. The genes that cause De Barsy syndrome have not been identified yet, although several studies have narrowed down the symptoms' cause. A study by Reversade et al. has shown that a mutation in PYCR1, the genetic sequence that codes for mitochondrial enzymes that break down proline, are prevalent in cases of autosomal recessive cutis laxa (ARCL), a condition very similar to De Barsy syndrome. A study by Leao-Teles et al. has shown that De Barsy syndrome may be related to mutations in ATP6V0A2 gene, known as ATP6V0A2-CDG by the new naming system.

Alternative names for De Barsy syndrome include corneal clouding-cutis laxa-mental retardation, cutis laxa-growth deficiency syndrome, De Barsy–Moens–Diercks syndrome, and progeroid syndrome of De Barsy.

Aplasia cutis congenita (ACC) is a rare disorder characterized by congenital absence of skin. Frieden classified ACC in 1986 into 9 groups on the basis of location of the lesions and associated congenital anomalies. The scalp is the most commonly involved area with lesser involvement of trunk and extremities. Frieden classified ACC with fetus papyraceus as type 5. This type presents as truncal ACC with symmetrical absence of skin in stellate or butterfly pattern with or without involvement of proximal limbs.]It is the most common congenital cicatricial alopecia, and is a congenital focal absence of epidermis with or without evidence of other layers of the skin.

The exact etiology of ACC is still unclear but intrauterine infection by varicella or herpes virus, drugs such as methimazole, misoprostol, valproate, cocaine, marijuana etc., fetus papyraceus, feto-fetal transfusion, vascular coagulation defects, amniotic membrane adherence, abnormal elastic fiber biomechanical forces and trauma are implicated. It can be associated with Johanson-Blizzard syndrome, Adams-Oliver syndrome, trisomy 13, and Wolf-Hirschhorn syndrome.

It can also seen with exposure to methimazole and carbimazole in utero. This dermatological manifestation has been linked to Peptidase D haploinsufficiency and a deletion in Chromosome 19.

Lenz–Majewski syndrome is a skin condition characterized by hyperostosis, craniodiaphyseal dysplasia, dwarfism, cutis laxa, proximal symphalangism, syndactyly, brachydactyly, mental retardation, enamel hypoplasia, and hypertelorism.

In 2013, whole-exome sequencing showed that a missense mutation resulting in overactive phosphatidylserine synthase 1 was the cause of LMS, making it the first known human disease to be caused by disrupted phosphatidylserine metabolism. The researchers suggested a link between the condition and bone metabolism.

This condition has been linked to mutations in the ribosomal GTPase BMS1 gene.

There are several disorders that share some characteristics with Ehlers–Danlos syndrome. For example, in cutis laxa the skin is loose, hanging, and wrinkled. In EDS, the skin can be pulled away from the body but is elastic and returns to normal when let go. In Marfan syndrome, the joints are very mobile and similar cardiovascular complications occur. People with EDS tend to have a "Marfanoid" appearance (e.g., tall, skinny, long arms and legs, "spidery" fingers). However, physical appearance and features in several types of Ehlers–Danlos syndrome also have characteristics including short stature, large eyes, and the appearance of a small mouth and chin, due to a small palate. The palate can have a high arch, causing dental crowding. Blood vessels can sometimes be easily seen through translucent skin, especially on the chest. The genetic connective tissue disorder, Loeys-Dietz Syndrome, also has symptoms that overlap with EDS.

In the past, Menkes disease, a copper metabolism disorder, was thought to be a form of Ehlers–Danlos syndrome. It is not uncommon for patients to be misdiagnosed with fibromyalgia, bleeding disorders or other disorders that can mimic EDS symptoms before a correct diagnosis is made. Because of these similar disorders and complications that can arise from an un-monitored case of EDS, a correct diagnosis is very important. Pseudoxanthoma elasticum (PXE) is worth consideration in diagnosing a patient.