Regular X-rays often fail to show the cystine stones, however they can be visualized in the diagnostic procedure that is called intravenous pyelogram (or IVP for short). Stones may show up on XR with a fuzzy gray appearance. They are radioopaque due to sulfur content, though more difficult to visualize than calcium oxalate stones.

Initial treatment is with adequate hydration, alkalization of the urine with citrate supplementation or acetazolamide, and dietary modification to reduce salt and protein intake (especially methionine). If this fails then patients are usually started on chelation therapy with an agent such as penicillamine. Tiopronin is another agent.

Once renal stones have formed, however, the first-line treatment is ESWL (Extracorporeal shock wave lithotripsy). If ESWL do not work efficiently surgery can be necessary. Both endoscopic surgery and conventional open-abdominal surgery have proven to be effective treatment modalities for patients with more advanced disease. Adequate hydration is the foremost aim of treatment to prevent cysteine stones. The goal is to increase the urine volume because the concentration of cystine in the urine is reduced which prevents cystine from precipitating from the urine and forming stones. People with cystine stones should consume 5 to 7 liters a day. The rationale behind alkalizing the urine is that cystine tends to stay in solution and causes no harm. In order to alkalize the urine, sodium biocarbonate has been used. One must be careful in alkalizing their urine because it could lead to other forms of stones in process of preventing cystine stones. Penicillamine is a drug that acts to form a complex with cystine that is 50 times more soluble than cystine itself. Percutaneous nephrolithotripsy (PNL) is performed via a port created by puncturing the kidney through the skin and enlarging the access port to 1 cm in diameter. Most of the time, cystine stones are too dense to be broken up by shock (ESWL) so PNL is needed.

Videos of surgery are available on various websites that show stone removal by percutaneous nephrolithotomy.

In February 2017, an article was published in Nature Medicine entitled 'Alpha lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria', suggesting that a high dose of the readily available antioxidant, alpha-lipoic acid at 2,700 mg/67 kg body weight daily reduced the incidence of stones. The effects were dose dependent. The results are unprecedented for cystinuria. A clinical trial is underway based on this mouse model.

Laboratory investigations typically carried out include:

- microscopic examination of the urine, which may show red blood cells, bacteria, leukocytes, urinary casts and crystals;

- urine culture to identify any infecting organisms present in the urinary tract and sensitivity to determine the susceptibility of these organisms to specific antibiotics;

- complete blood count, looking for neutrophilia (increased neutrophil granulocyte count) suggestive of bacterial infection, as seen in the setting of struvite stones;

- renal function tests to look for abnormally high blood calcium blood levels (hypercalcemia);

- 24 hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate and phosphate;

- collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple tea strainer) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.

In people with a history of stones, those who are less than 50 years of age and are presenting with the symptoms of stones without any concerning signs do not require helical CT scan imaging. A CT scan is also not typically recommended in children.

Otherwise a noncontrast helical CT scan with sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis. All stones are detectable on CT scans except very rare stones composed of certain drug residues in the urine, such as from indinavir. Calcium-containing stones are relatively radiodense, and they can often be detected by a traditional radiograph of the abdomen that includes the kidneys, ureters, and bladder (KUB film). Some 60% of all renal stones are radiopaque. In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. Cystine calculi are only faintly radiodense, while uric acid stones are usually entirely radiolucent.

Where a CT scan is unavailable, an intravenous pyelogram may be performed to help confirm the diagnosis of urolithiasis. This involves intravenous injection of a contrast agent followed by a KUB film. Uroliths present in the kidneys, ureters or bladder may be better defined by the use of this contrast agent. Stones can also be detected by a retrograde pyelogram, where a similar contrast agent is injected directly into the distal ostium of the ureter (where the ureter terminates as it enters the bladder).

Renal ultrasonography can sometimes be useful, as it gives details about the presence of hydronephrosis, suggesting the stone is blocking the outflow of urine. Radiolucent stones, which do not appear on KUB, may show up on ultrasound imaging studies. Other advantages of renal ultrasonography include its low cost and absence of radiation exposure. Ultrasound imaging is useful for detecting stones in situations where X-rays or CT scans are discouraged, such as in children or pregnant women. Despite these advantages, renal ultrasonography in 2009 was not considered a substitute for noncontrast helical CT scan in the initial diagnostic evaluation of urolithiasis. The main reason for this is that compared with CT, renal ultrasonography more often fails to detect small stones (especially ureteral stones), as well as other serious disorders that could be causing the symptoms. A 2014 study confirmed that ultrasonography rather than CT as an initial diagnostic test results in less radiation exposure and did not find any significant complications.

The duplication involved in PTLS is usually large enough to be detected through G-banding alone, though there is a high false negative rate. To ascertain the diagnosis when karyotyping results are unclear or negative, more sophisticated techniques such as subtelomeric fluorescent in-situ hybridization analysis and array comparative genomic hybridization (aCGH) may be used.

The brain is usually grossly abnormal in outline when someone is diagnosed with Miller–Dieker syndrome. Only a few shallow sulci and shallow Sylvian fissures are seen; this takes on an hourglass or figure-8 appearance on the axial imaging. The thickness and measurement for a person without MDS is 3–4 mm. With MDS, a person's cortex is measured at 12–20 mm.

While no cure for MDS is available yet, many complications associated with this condition can be treated, and a great deal can be done to support or compensate for functional disabilities. Because of the diversity of the symptoms, it can be necessary to see a number of different specialists and undergo various examinations, including:

- Developmental evaluation

- Cardiologists evaluation

- Otolaryngology

- Treatment of seizures

- Urologic evaluation

- Genetic counseling-balanced chromosomal translocation should be excluded in a parents with an affected child are planning another pregnancy, so parents with affected children should visit a genetic counselor.

McLeod syndrome is one of only a few disorders in which acanthocytes may be found on the peripheral blood smear. Blood evaluation may show signs of hemolytic anemia. Elevated creatine kinase can be seen with myopathy in McLeod syndrome.

A typical patient with severe McLeod syndrome that begins in adulthood lives for an additional 5 to 10 years. Patients with cardiomyopathy have elevated risk for congestive heart failure and sudden cardiac death. The prognosis for a normal life span is often good in some patients with mild neurological or cardiac sequelae.

The diagnosis of this syndrome can be made on clinical examination and perinatal autopsy.

Koenig and Spranger (1986) noted that eye lesions are apparently nonobligatory components of the syndrome. The diagnosis of Fraser syndrome should be entertained in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos. Thomas et al. (1986) also emphasized the occurrence of the cryptophthalmos syndrome without cryptophthalmos and proposed diagnostic criteria for Fraser syndrome. Major criteria consisted of cryptophthalmos, syndactyly, abnormal genitalia, and positive family history. Minor criteria were congenital malformation of the nose, ears, or larynx, cleft lip and/or palate, skeletal defects, umbilical hernia, renal agenesis, and mental retardation. Diagnosis was based on the presence of at least 2 major and 1 minor criteria, or 1 major and 4 minor criteria.

Boyd et al. (1988) suggested that prenatal diagnosis by ultrasound examination of eyes, digits, and kidneys should detect the severe form of the syndrome. Serville et al. (1989) demonstrated the feasibility of ultrasonographic diagnosis of the Fraser syndrome at 18 weeks' gestation. They suggested that the diagnosis could be made if 2 of the following signs are present: obstructive uropathy, microphthalmia, syndactyly, and oligohydramnios. Schauer et al. (1990) made the diagnosis at 18.5 weeks' gestation on the basis of sonography. Both the female fetus and the phenotypically normal father had a chromosome anomaly: inv(9)(p11q21). An earlier born infant had Fraser syndrome and the same chromosome 9 inversion.

Van Haelst et al. (2007) provided a revision of the diagnostic criteria for Fraser syndrome according to Thomas et al. (1986) through the addition of airway tract and urinary tract anomalies to the major criteria and removal of mental retardation and clefting as criteria. Major criteria included syndactyly, cryptophthalmos spectrum, urinary tract abnormalities, ambiguous genitalia, laryngeal and tracheal anomalies, and positive family history. Minor criteria included anorectal defects, dysplastic ears, skull ossification defects, umbilical abnormalities, and nasal anomalies. Cleft lip and/or palate, cardiac malformations, musculoskeletal anomalies, and mental retardation were considered uncommon. Van Haelst et al. (2007) suggested that the diagnosis of Fraser syndrome can be made if either 3 major criteria, or 2 major and 2 minor criteria, or 1 major and 3 minor criteria are present in a patient.

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

Potocki–Shaffer syndrome can be detected through array comparative genomic hybridization (aCGH).

Some symptoms can be managed with drug therapy, surgery and rehabilitation, genetic counselling, and palliative care.

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.

A clinical diagnosis of SCS can be verified by testing the TWIST1 gene (only gene in which mutations are known to cause SCS) for mutations using DNA analysis, such as sequence analysis, deletion/duplication analysis, and cytogenetics/ FISH analysis. Sequence analysis of exon 1 (TWIST1 coding region) provides a good method for detecting the frequency of mutations in the TWIST1 gene. These mutations include nonsense, missense, splice site mutation, and intragenic deletions/insertions. Deletion/duplication analysis identifies mutations in the TWIST1 gene that are not readily detected by sequence analysis. Common methods include PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA). Cytogenetic/FISH analysis attaches fluorescently labels DNA markers to a denatured chromosome and is then examined under fluorescent lighting, which reveals mutations caused by translocations or inversions involving 7p21. Occasionally, individuals with SCS have a chromosome translocation, inversion, or ring chromosome 7 involving 7p21 resulting in atypical findings, such as, increased developmental delay. Individuals with SCS, typically have normal brain functioning and rarely have mental impairments. For this reason, if an individual has both SCS and mental retardation, then they should have their TWIST1 gene screened more carefully because this is not a normal trait of SCS. Cytogenetic testing and direct gene testing can also be used to study gene/chromosome defects. Cytogenetic testing is the study of chromosomes to detect gains or losses of chromosomes or chromosome segments using fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization (CGH). Direct gene testing uses blood, hair, skin, amniotic fluid, or other tissues in order to find genetic disorders. Direct gene testing can determine whether an individual has SCS by testing the individual's blood for mutations in the TWIST1 gene.

Y chromosome microdeletion is currently diagnosed by extracting DNA from leukocytes in a man's blood sample, mixing it with some of the about 300 known genetic markers for sequence-tagged sites (STS) on the Y chromosome, and then using polymerase chain reaction amplification and gel electrophoresis in order to test whether the DNA sequence corresponding to the selected markers is present in the DNA.

Such procedures can test only the integrity of a tiny part of the overall 23 million base pair long Y chromosome, therefore the sensitivity of such tests depends on the choice and number of markers used. Present diagnostic techniques can only discover certain types of deletions and mutations on a chromosome and give therefore no complete picture of genetic causes of infertility. They can only demonstrate the presence of some defects, but not the absence of any possible genetic defect on the chromosome.

The gold standard test for genetic mutation, namely complete DNA sequencing of a patient's Y chromosome, is still far too expensive for use in epidemiologic research or even clinical diagnostics.

The disorder is treated by strictly reducing the intake of foods rich in plant sterols (e.g., vegetable oils, olives and avocados). However, dietary therapy is often never fully sufficient to control this disease since plant sterols are constituents of all plant-based foods. Statins have been used, and while these lower cholesterol levels and may ameliorate atherosclerotic disease, plant sterol levels are insufficiently lowered by their use alone.

If dietary treatment alone is insufficient, bile acid-binding resins (e.g., cholestyramine, colestipol) could be considered. In October 2002, a new cholesterol absorption inhibitor, ezetimibe, received US Food and Drug Administration (FDA) approval for use in sitosterolemia. This drug is now the standard of care, as it blocks sterol entry and can be used in combination with bile-acid resins.

Finally, ileal bypass has been performed in select cases to decrease the levels of plant sterols in the body, though this therapy was undertaken prior to the advent of ezetimibe.

While the disease manifests early in life in most cases, diagnosis of the disease is often quite delayed. The symptoms that affected patients present vary, but the most common presenting symptoms are gastrointestinal issues such as nausea, vomiting, abdominal pain, and diarrhea, and neurologic or ocular symptoms such as hearing loss, weakness, and peripheral neuropathy. These gastrointestinal symptoms cause patients with MNGIE to be very thin and experience persistent weight loss and this often leads to MNGIE being misdiagnosed as an eating disorder. These symptoms without presentation of disordered eating and warped body image warrant further investigation into the possibility of MNGIE as a diagnosis. Presentation of these symptoms and lack of disordered eating are not enough for a diagnosis. Radiologic studies showing hypoperistalsis, large atonic stomach, dilated duodenum, diverticula, and white matter changes are required to confirm the diagnosis. Elevated blood and urine nucleoside levels are also indicative of MNGIE syndrome. Abnormal nerve conduction as well as analysis of mitochondria from liver, intestines, muscle, and nerve tissue can also be used to support the diagnosis.

A successful treatment for MNGIE has yet to be found, however, symptomatic relief can be achieved using pharmacotherapy and celiac plexus neurolysis. Celiac plexus neurolysis involves interrupting neural transmission from various parts of the gastrointestinal tract. By blocking neural transmission, pain is relieved and gastrointestinal motility increases. Stem cell therapies are currently being investigated as a potential cure for certain patients with the disease, however, their success depends on physicians catching the disease early before too much organ damage has occurred.

SMS is usually confirmed by blood tests called chromosome (cytogenetic) analysis and utilize a technique called FISH (fluorescent in situ hybridization). The characteristic micro-deletion was sometimes overlooked in a standard FISH test, leading to a number of people with the symptoms of SMS with negative results.

The recent development of the FISH for 17p11.2 deletion test has allowed more accurate detection of this deletion. However, further testing is required for variations of Smith–Magenis syndrome that are caused by a mutation of the "RAI1" gene as opposed to a deletion.

Children with SMS are often given psychiatric diagnoses such as autism, attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), attention deficit disorder (ADD) and/or mood disorders.

As mentioned, permissive hypotension is unwise. Especially if the crushing weight is on the patient more than 4 hours, but often if it persists more than one hour, careful fluid overload is wise, as well as the administration of intravenous sodium bicarbonate. The San Francisco emergency services protocol calls for a basic adult dose of a 2 L bolus of normal saline followed by 500 ml/h, limited for "pediatric patients and patients with history of cardiac or renal dysfunction."

If the patient cannot be fluid loaded, this may be an indication for a tourniquet to be applied.

Microdeletions in the Y chromosome have been found at a much higher rate in infertile men than in fertile controls and the correlation found may still go up as improved genetic testing techniques for the Y chromosome are developed.

Much study has been focused upon the "azoospermia factor locus" (AZF), at Yq11. A specific partial deletion of AZFc called "gr/gr deletion" is significantly associated with male infertility among Caucasians in Europe and the Western Pacific region.

Additional genes associated with spermatogenesis in men and reduced fertility upon Y chromosome deletions include RBM, DAZ, SPGY, and TSPY.

Treatment of cause: Due to the genetic cause, no treatment of the cause is possible.

Treatment of manifestations: routine treatment of ophthalmologic, cardiac, and neurologic findings; speech, occupational, and physical therapies as appropriate; specialized learning programs to meet individual needs; antiepileptic drugs or antipsychotic medications as needed.

Surveillance: routine pediatric care; routine developmental assessments; monitoring of specific identified medical issues.

Up until recently, experts frequently disagreed on whether a patient had SCS, Crouzon syndrome, isolated craniosynostosis, or some other disease because the symptoms are so closely related, they literally had no way of differentiating between all of them. However, we now have direct gene testing, which allows for a more definitive diagnosis because it allows them to be differentiated from each other based on which gene is mutated in each condition. The following is a list of conditions commonly confused/misdiagnosed for SCS, some of their symptoms, and which mutated gene each contains:

Around 80 cases have been reported in the literature worldwide, hence this condition appears to be relatively rare. More than likely, sitosterolemia is significantly underdiagnosed and many patients are probably misdiagnosed with hyperlipidemia.

The clinician must protect the patient against hypotension, renal failure, acidosis, hyperkalemia and hypocalcemia. Admission to an intensive care unit, preferably one experienced in trauma medicine, may be appropriate; even well-seeming patients need observation. Treat open wounds as surgically appropriate, with debridement, antibiotics and tetanus toxoid; apply ice to injured areas.

Intravenous hydration of up to 1.5 L/hour should continue to prevent hypotension. A urinary output of at least 300 ml/hour should be maintained with IV fluids and mannitol, and hemodialysis considered if this amount of diuresis is not achieved. Use intravenous sodium bicarbonate to keep the urine pH at 6.5 or greater, to prevent myoglobin and uric acid deposition in kidneys.

To prevent hyperkalemia/hypocalcemia, consider the following adult doses:

- calcium gluconate 10% 10ml or calcium chloride 10% 5 ml IV over 2 minutes

- sodium bicarbonate 1 meq/kg IV slow push

- regular insulin 5–10 U

- 50% glucose 1–2 ampules IV bolus

- kayexalate 25–50 g with sorbitol 20% 100 ml by mouth or rectum.

Even so, cardiac arrhythmias may develop; electrocardiographic monitoring is advised, and specific treatment begun promptly.

The incidence of Fraser syndrome is 0.043 per 10,000 live born infants and 1.1 in 10,000 stillbirths, making it a rare syndrome.