Carrier testing for Roberts syndrome requires prior identification of the disease-causing mutation in the family. Carriers for the disorder are heterozygotes due to the autosomal recessive nature of the disease. Carriers are also not at risk for contracting Roberts syndrome themselves. A prenatal diagnosis of Roberts syndrome requires an ultrasound examination paired with cytogenetic testing or prior identification of the disease-causing ESCO2 mutations in the family.

Screening generally only takes place among those displaying several of the symptoms of ABCD, but a study on a large group of institutionalized deaf people in Columbia revealed that 5.38% of them were Waardenburg patients. Because of its rarity, none of the patients were diagnosed with ABCD (Waardenburg Type IV). Nothing can be done to prevent the disease.

Genetic testing may be available for mutations in the FGDY1 gene. Genetic counseling is indicated for individuals or families who may carry this condition, as there are overlapping features with fetal alcohol syndrome.

Other examinations or tests can help with diagnosis. These can include:

detailed family history

- conducting a detailed physical examination to document morphological features

- testing for genetic defect in FGDY1

- x-rays can identify skeletal abnormalities

- echo cardiogram can screen for heart abnormalities

- CT scan of the brain for cystic development

- X-ray of the teeth

- Ultrasound of abdomen to identify undescended testis

The occurrence of WS has been reported to be one in 45,000 in Europe. The diagnosis can be made prenatally by ultrasound due to the phenotype displaying pigmentary disturbances, facial abnormalities, and other developmental defects. After birth, the diagnosis is initially made symptomatically and can be confirmed through genetic testing. If the diagnosis is not made early enough, complications can arise from

Hirschsprung's disease.

Diagnosis depends on the clinical scenario. However, karyotyping is an essential test for diagnosis.

Diagnosis is made based on features as well as by the very early onset of serious eye and ear disease. Because Marshall syndrome is an autosomal dominant hereditary disease, physicians can also note the characteristic appearance of the biological parent of the child. There are no tests for Stickler syndrome or Marshall syndrome. Some families with Stickler syndrome have been shown to have mutations in the Type II collagen gene on chromosome 1. However, other families do not show the linkage to the collagen gene. It is an area of active research, also the genetic testing being expensive supports that the diagnosis is made depending on the features.

Cytogenetic preparations that have been stained by either Giemsa or C-banding techniques will show two characteristic chromosomal abnormalities. The first chromosomal abnormality is called premature centromere separation (PCS) and is the most likely pathogenic mechanism for Roberts syndrome. Chromosomes that have PCS will have their centromeres separate during metaphase rather than anaphase (one phase earlier than normal chromosomes). The second chromosomal abnormality is called heterochromatin repulsion (HR). Chromosomes that have HR experience separation of the heterochromatic regions during metaphase. Chromosomes with these two abnormalities will display a "railroad track" appearance because of the absence of primary constriction and repulsion at the heterochromatic regions. The heterochromatic regions are the areas near the centromeres and nucleolar organizers. Carrier status cannot be determined by cytogenetic testing. Other common findings of cytogenetic testing on Roberts syndrome patients are listed below.

- Aneuploidy- the occurrence of one or more extra or missing chromosomes

- Micronucleation- nucleus is smaller than normal

- Multilobulated Nuclei- the nucleus has more than one lobe

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.

In general, children with a small isolated nevus and a normal physical exam do not need further testing; treatment may include potential surgical removal of the nevus. If syndrome issues are suspected, neurological, ocular, and skeletal exams are important. Laboratory investigations may include serum and urine calcium and phosphate, and possibly liver and renal function tests. The choice of imaging studies depends on the suspected abnormalities and might include skeletal survey, CT scan of the head, MRI, and/or EEG.

Depending on the systems involved, an individual with Schimmelpenning syndrome may need to see an interdisciplinary team of specialists: dermatologist, neurologist, ophthalmologist, orthopedic surgeon, oral surgeon, plastic surgeon, psychologist.

Diagnosis of Harlequin syndrome is made when the individual has consistent signs and symptoms of the condition, therefore, it is made by clinical observation. In addition, a neurologist or primary care physician may require an MRI test to rule out similar disorders such as Horner's syndrome, Adie's syndrome, and Ross' syndrome. In an MRI, a radiologist may observe areas near brain or spinal cord for lesions, or any damage to the nerve endings. It is also important that the clinician rules out traumatic causes by performing autonomic function tests. Such tests includes the following: tilt table test, orthostatic blood pressure measurement, head-up test, valsalva maneuver, thermoregulatory sweat test, tendon reflex test, and electrocardiography (ECG). CT scan of the heart and lungs may also be performed to rule out a structural underlying lesion. The medical history of the individual should be carefully noted.

Many professionals that are likely to be involved in the treatment of those with Stickler's syndrome, include anesthesiologists, oral and maxillofacial surgeons; craniofacial surgeons; ear, nose, and throat specialists, ophthalmologists, optometrists, audiologists, speech pathologists, physical therapists and rheumatologists.

In terms of diagnosing Bannayan–Riley–Ruvalcaba syndrome there is no current method outside the physical characteristics that may be present as signs/symptoms. There are, however, multiple molecular genetics tests (and cytogenetic test) to determine Bannayan–Riley–Ruvalcaba syndrome.

There is no medical treatment for either syndrome but there are some recommendations that can help with prevention or early identification of some of the problems. Children with either syndrome should have their hearing tested, and adults should be aware that the hearing loss may not develop until the adult years. Yearly visits to an ophthalmologist or other eye care professional who has been informed of the diagnosis of Stickler or Marshall syndrome is important for all affected individuals. Children should have the opportunity to have myopia corrected as early as possible, and treatment for cataracts or detached retinas may be more effective with early identification. Support for the joints is especially important during sports, and some recommend that contact sports should be avoided by those who have very loose joints.

Diagnosis of oculocerebrorenal syndrome can be done via genetic testing Among the different investigations that can de done are:

- Urinalysis

- MRI

- Blood test

It is suggested that the diagnostic criteria for Malpuech syndrome should include cleft lip and/or palate, typical associated facial features, and at least two of the following: urogenital anomalies, caudal appendage, and growth or developmental delay.

Due to the relatively high rate of hearing impairment found with the disorder, it too may be considered in the diagnosis. Another congenital disorder, Wolf-Hirschhorn (Pitt-Rogers-Danks) syndrome, shares Malpuech features in its diagnostic criteria. Because of this lacking differentiation, karyotyping (microscopic analysis of the chromosomes of an individual) can be employed to distinguish the two. Whereas deletions in the short arm of chromosome 4 would be revealed with Wolf-Hirschhorn, a karyotype without this aberration present would favor a Malpuech syndrome diagnosis. Also, the karyotype of an individual with Malpuech syndrome alone will be normal.

About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated. In the United States, termination rates are around 67%, but this rate varied from 61% to 93% among different populations evaluated. When nonpregnant people are asked if they would have a termination if their fetus tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and when women who screened positive are asked, 89–97% say yes.

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.

Some people may have some mental slowness, but children with this condition often have good social skills. Some males may have problems with fertility.

Orofaciodigital syndrome type 1 is diagnosed through genetic testing. Some symptoms of Orofaciodigital syndrome type 1 are oral features such as, split tongue, benign tumors on the tongue, cleft palate, hypodontia and other dental abnormalities. Other symptoms of the face include hypertelorism and micrognathia. Bodily abnormalities such as webbed, short, joined, or abnormally curved fingers and toes are also symptoms of Orofaciodigital syndrome type 1. The most frequent symptoms are accessory oral frenulum, broad alveolar ridges, frontal bossing, high palate, hypertelorism, lobulated tongue, median cleft lip, and wide nasal bridge. Genetic screening of the OFD1 gene is used to officially diagnose a patient who has the syndrome, this is detected in 85% of individuals who are suspected to have Orofaciodigital syndrome type 1.

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.

The diagnosis of Muenke syndrome is suspected bases on abnormal skull shape and a diagnosis of coronal craniosynostosis. In 2006, Agochukwu and her colleagues concluded that “A distinct Muenke syndrome phenotype includes: uni or bilateral coronal synostosis, midface hypoplasia, broad toes, and brachydactyly.” Due to phenotypic overlap and/or mild phenotypes, clinical differentiation of this syndrome may be difficult. The suspected diagnosis is confirmed by a blood test to check for gene mutation. To establish the extent of disease in an individual diagnosed with Muenke syndrome, various evaluations are recommended.

In August 2016, researchers at the Instituto de Assistência dos Servidores do Estado do Rio de Janeiro used botulinum toxin as a method to block the acetylcholine release from the presynaptic neurons. Although they have seen a reduction in one sided flushing, sweating still occurs.

There have been case studies of individuals whom have experienced this syndrome after an operation. Two patients, a 37-year-old and 58-year-old female patients suffering from metastatic cancer were scheduled for placement of an intrathecal pump drug delivery system. After the intrathecal pump was placed, certain medications were given to the patients. Once the medications were administered, both patients had one sided facial flushes, closely resembling Harlequin Syndrome. Patients were given neurological exams to confirm that their nerves were still intact. An MRI was performed and showed no significant evidence of bleeding or nerve compression. After close observation for 16 hours, symptoms of the Harlequin syndrome was diminished and both patients did not have another episode.

Another case study was based on a 6-year-old male visiting an outpatient setting for one sided flushes during or after physical activity or exposed to heat. Vitals, laboratory tests, and CT scans were normal. Along with the flushes, the right pupil was 1.5 mm in size, while the left pupil was 2.5 mm in size; however, no ptosis, miosis, or enophthalmos was noted. The patient also had an MRI scan to rule out any lesion near the brain or spinal cord. No abnormalities were noted and the patient did not receive any treatments. The patient was diagnosed with idiopathic Harlequin syndrome.

Although the mechanism is still unclear, the pathophysiology of this condition, close monitoring, and reassurance are vital factors for successful management.

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.

Since Usher syndrome is incurable at present, it is helpful to diagnose children well before they develop the characteristic night blindness. Some preliminary studies have suggested as many as 10% of congenitally deaf children may have Usher syndrome. However, a misdiagnosis can have bad consequences.

The simplest approach to diagnosing Usher syndrome is to test for the characteristic chromosomal mutations. An alternative approach is electroretinography, although this is often disfavored for children, since its discomfort can also make the results unreliable. Parental consanguinity is a significant factor in diagnosis. Usher syndrome I may be indicated if the child is profoundly deaf from birth and especially slow in walking.

Thirteen other syndromes may exhibit signs similar to Usher syndrome, including Alport syndrome, Alstrom syndrome, Bardet-Biedl syndrome, Cockayne syndrome, spondyloepiphyseal dysplasia congenita, Flynn-Aird syndrome, Friedreich ataxia, Hurler syndrome (MPS-1), Kearns-Sayre syndrome (CPEO), Norrie syndrome, osteopetrosis (Albers-Schonberg disease), Refsum's disease (phytanic acid storage disease), and Zellweger syndrome (cerebrohepatorenal syndrome).

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

- Endoscopic

- CT scan

- Serum endocrine autoantibody screen

- Histologic test