Diagnosis involves consideration of physical features and genetic testing. Presence of split uvula is a differentiating characteristic from Marfan Syndrome, as well as the severity of the heart defects. Loeys-Dietz Syndrome patients have more severe heart involvement and it is advised that they be treated for enlarged aorta earlier due to the increased risk of early rupture in Loeys-Dietz patients. Because different people express different combinations of symptoms and the syndrome was identified in 2005, many doctors may not be aware of its existence, although clinical guidelines were released in 2014-2015. Dr. Harold Dietz, Dr. Bart Loeys, and Dr. Kenneth Zahka are considered experts in this condition.

A 2007 study followed 112 individuals for a mean of 12 years (mean age 25.3, range 12–71). No patient died during follow-up, but several required medical interventions. The mean final heights were 167 and 153 cm for men and women, respectively, which is approximately 2 standard deviations below normal.

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.

During pregnancy, even in the absence of preconception cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection, which is often fatal even when rapidly treated. Women with Marfan syndrome, then, should receive a thorough assessment prior to conception, and echocardiography should be performed every six to 10 weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.

Marfan syndrome is expressed dominantly. This means a child with one parent a bearer of the gene has a 50% probability of getting the syndrome. In 1996, the first preimplantation genetic testing (PGT) therapy for Marfan was conducted; in essence PGT means conducting a genetic test on early-stage IVF embryo cells and discarding those embryos affected by the Marfan mutation.

First trimester ultrasound of noonan syndrome reveals nuchal oedema / cystic hygroma almost same as seen in Turner syndrome. Follow up scans may shows clinical features that already described above.

A study shows this disease is also associated with hepato splenomegaly with renal anomalies including malrotation and solitary kidney. A rare incidence of choledochal cyst is also reported as well.

Even though clinical diagnostic criteria have not been 100 percent defined for genitopatellar syndrome, the researchers stated that the certain physical features could relate to KAT6B mutation and result in the molecular genetic testing. The researchers stated that the Individuals with two major features or one major feature and two minor features are likely to have a KAT6B mutation.

To diagnose the Genitopatellar Syndrome, there are multiple ways to evaluate.

Medical genetics consultation

- Evaluation by developmental specialist

- Feeding evaluation

- Baseline hearing evaluation

- Thyroid function tests

- Evaluation of males for cryptorchidism

- Orthopedic evaluation if contractures are present or feet/ankles are malpositioned

- Hip radiographs to evaluate for femoral head dislocation

- Renal ultrasound examination for hydronephrosis and cysts

- Echocardiogram for congenital heart defects

- Evaluation for laryngomalacia if respiratory issues are present

- Evaluation by gastroenterologist as needed, particularly if bowel malrotation is suspected

The presence of the disease can be confirmed with a genetic test. In a study of 10 infants with clinical indications of NSML prior to their first birthday, 8 (80%) patients were confirmed to have the suspected mutation. An additional patient with the suspected mutation was subsequently found to have NF1, following evaluation of the mother.

There are 5 identified allelic variants responsible for NSML. Y279C, T468M, A461T, G464A, and Q510P which seems to be a unique familial mutation, in that all other variants are caused by transition errors, rather than transversion.

This includes Ataxia-telegiectasia, Chédiak-Higashi syndrome, DiGeorge syndrome, Griscelli syndrome and Marinesco-Sjogren syndrome.

In 2010 the Ghent nosology was revised, and new diagnostic criteria superseded the previous agreement made in 1996. The seven new criteria can lead to a diagnosis:

In the absence of a family history of MFS:

1. Aortic root Z-score ≥ 2 AND ectopia lentis

2. Aortic root Z-score ≥ 2 AND an FBN1 mutation

3. Aortic root Z-score ≥ 2 AND a systemic score* > 7 points

4. Ectopia lentis AND an FBN1 mutation with known aortic pathology

In the presence of a family history of MFS (as defined above):

1. Ectopia lentis

2. Systemic score* ≥ 7

3. Aortic root Z-score ≥ 2

- Points for systemic score:

- Wrist AND thumb sign = 3 (wrist OR thumb sign = 1)

- Pectus carinatum deformity = 2 (pectus excavatum or chest asymmetry = 1)

- Hindfoot deformity = 2 (plain pes planus = 1)

- Dural ectasia = 2

- Protrusio acetabuli = 2

- pneumothorax = 2

- Reduced upper segment/lower segment ratio AND increased arm/height AND no severe scoliosis = 1

- Scoliosis or thoracolumbar kyphosis = 1

- Reduced elbow extension = 1

- Facial features (3/5) = 1 (dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia)

- Skin striae (stretch marks) = 1

- Myopia > 3 diopters = 1

- Mitral valve prolapse 1⁄4 1

The thumb sign (Steinberg's sign) is elicited by asking the patient to flex the thumb as far as possible and then close the fingers over it. A positive thumb sign is where the entire distal phalanx is visible beyond the ulnar border of the hand, caused by a combination of hypermobility of the thumb as well as a thumb which is longer than usual.

The wrist sign (Walker's sign) is elicited by asking the patient to curl the thumb and fingers of one hand around the other wrist. A positive wrist sign is where the little finger and the thumb overlap, caused by a combination of thin wrists and long fingers.

The diagnostic work up usually includes and MRI of the brain, an EEG, ophthalmic examination and a cardiac ECHO.

Muscle biopsy - which is not commonly done - may show storage of abnormal material and secondary mitochondrial abnormalities in skeletal muscle. Other features that may be seen on muscle biopsy include variability in fibre size, increase in internal and centralized nuclei, type 1 fibre hypotrophy with normally sized type 2 fibres, increased glycogen storage and variable vacuoles on light microscopy

The diagnosis is confirmed by sequencing of the EPG5.

In itself, NSML is not a life-threatening diagnosis, most people diagnosed with the condition live normal lives. Obstructive cardiomyopathy and other pathologic findings involving the cardiovascular system may be a cause of death in those whose cardiac deformities are profound.

The only treatment for MWS is only symptomatic, with multidisciplinary management

The complete or partial absence of the pectoralis muscle is the malformation that defines Poland Syndrome. It can be treated by inserting a custom implant designed by CAD (computer aided design). A 3D reconstruction of the patient's chest is performed from a medical scanner to design a virtual implant perfectly adapted to the anatomy of each one. The implant is made of medical silicone unbreakable rubber. This treatment is purely cosmetic and does not make up for the patient's imbalanced upper body strength.

The Poland syndrome malformations being morphological, correction by custom implant is a first-line treatment. This technique allows a wide variety of patients to be treated with good outcomes. Poland Syndrome can be associated with bones, subcutaneous and mammary atrophy: if the first, as for pectus excavatum, is successfully corrected by a custom implant, the others can require surgical intervention such as lipofilling or silicone breast implant, in a second operation.

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.

There have been 30 cases of Marden-Walker Syndrome reported since 1966. The first case of this was in 1966 a female infant was diagnosed with blepharophimosis, joint contractures, arachnodactyly and growth development delay. She ended up passing at 3 months due to pneumonia.

Laboratory testing reveals multiple mutations of HCS. Two genetic variants result in sporadic HCS symptoms, which are HCS-02 and HCS-03. These mutations produce symptoms that come and go, but have been present "de novo". HCS-03 was identified as the variant that is passed through afflicted family members and presents symptoms throughout the lifetime of the individual. All variants of HCS lead to the same premature termination of PEST sequences which compromise normal function of "NOTCH2". "NOTCH" has four different receptors, which have an affinity for similar ligands. They are classified as single-pass transmembrane receptors.

As there is no known cure, Loeys–Dietz syndrome is a lifelong condition. Due to the high risk of death from aortic aneurysm rupture, patients should be followed closely to monitor aneurysm formation, which can then be corrected with interventional radiology or vascular surgery.

Previous research in laboratory mice has suggested that the angiotensin II receptor antagonist losartan, which appears to block TGF-beta activity, can slow or halt the formation of aortic aneurysms in Marfan syndrome. A large clinical trial sponsored by the National Institutes of Health is currently underway to explore the use of losartan to prevent aneurysms in Marfan syndrome patients. Both Marfan syndrome and Loeys–Dietz syndrome are associated with increased TGF-beta signaling in the vessel wall. Therefore, losartan also holds promise for the treatment of Loeys–Dietz syndrome. In those patients in which losartan is not halting the growth of the aorta, irbesartan has been shown to work and is currently also being studied and prescribed for some patients with this condition.

If an increased heart rate is present, atenolol is sometimes prescribed to reduce the heart rate to prevent any extra pressure on the tissue of the aorta. Likewise, strenuous physical activity is discouraged in patients, especially weight lifting and contact sports.

Diagnosis of MSS is based on clinical symptoms, magnetic resonance imaging (MRI) of the brain (cerebellar atrophy particularly involving the cerebellar vermis), and muscle biopsy.

It can be associated with mutations of the SIL1 gene, and a mutation can be found in about 50% of cases.

Differential diagnosis includes Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN), Marinesco–Sjögren like syndrome with chylomicronemia, carbohydrate deficient glycoprotein syndromes, Lowe syndrome, and mitochondrial disease.

Prognoses for 3C syndrome vary widely based on the specific constellation of symptoms seen in an individual. Typically, the gravity of the prognosis correlates with the severity of the cardiac abnormalities. For children with less severe cardiac abnormalities, the developmental prognosis depends on the cerebellar abnormalities that are present. Severe cerebellar hypoplasia is associated with growth and speech delays, as well as hypotonia and general growth deficiencies.

Kabuki syndrome can be diagnosed using whole exome or whole genome sequencing. Some patients who were initially clinically diagnosed with Kabuki syndrome were actually found to have Wiedemann-Steiner syndrome.

The surgery takes place under general anaesthesia and lasts less than 1 hour. The surgeon prepares the locus to the size of the implant after performing a 8-cm axillary incision and inserts the implant beneath the skin. The closure is made in 2 planes.

The implant will replace the pectoralis major muscle, thus enabling the thorax to be symmetrical and, in women, the breast as well. If necessary, especially in the case of women, a second operation will complement the result by the implantation of a breast implant and / or lipofilling.

Lipomodelling is progressively used in the correction of breast and chest wall deformities. In Poland syndrome, this technique appears to be a major advance that will probably revolutionize the treatment of severe cases. This is mainly due to its ability to achieve previously unachievable quality of reconstruction with minimal scaring.

The treatment for Morquio syndrome consists of prenatal identification and of enzyme replacement therapy. On 12 February 2014, the US Food and Drug Administration approved the drug elosulfase alfa (Vimizim) for treating the disease.

There are no treatment to return to its normal functions. However, there are treatments for the different symptoms.

For the Developmental symptoms, Educational intervention and speech therapy beginning in infancy could help to reduce the high risk for motor, cognitive, speech, and language delay

For theSkeletal features, referral to an orthopedist for consideration of surgical release of contractures. In addition,early referral to physical therapy could help increase joint mobility.

Lastly, Thyroid hormone replacement could help out the thyroid dysfunction

Diagnosis should be based on the clinical and radiographic findings and a genetic analysis can be assessed.

Marshall–Smith syndrome is not to be confused with:

- Marshall syndrome (aka.Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA syndrome, see also: Periodic fever syndrome)

- Sotos (like) syndrome

- Weaver-Smith syndrome (WSS)