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.

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.

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.

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.

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 outcome of this disease is dependent on the severity of the cardiac defects. Approximately 1 in 3 children with this diagnosis require shunting for the hydrocephaly that is often a consequence. Some children require extra assistance or therapy for delayed psychomotor and speech development, including hypotonia.

According to the Williams Syndrome Association, diagnosis of Williams syndrome begins with recognition of physical symptoms and markers, which is followed by a confirmatory genetic test. The physical signs that often indicate a suspected case of Williams syndrome include puffiness around the eyes, a long philtrum, and a pattern in the iris. Physiological symptoms that often contribute to a Williams syndrome diagnosis are cardiovascular problems, particularly aortic or pulmonary stenosis, as well as feeding disturbance in infants. Developmental delays are often taken as an initial sign of the syndrome, as well.

If a physician suspects a case of Williams syndrome, the diagnosis is confirmed using one of two possible genetic tests: micro-array analysis or the fluorescent in situ hybridization (FISH) test. The FISH test examines chromosome #7 and probes for the existence of two copies of the elastin gene. Since 98-99% of individuals with Williams syndrome lack half of the 7q11.23 region of chromosome #7, where the elastin gene is located, the presence of only one copy of the gene is a strong sign of the syndrome. This confirmatory genetic test has been validated in epidemiological studies of the syndrome, and has been demonstrated to be a more effective method of identifying Williams syndrome than previous methods, which often relied on the presence of cardiovascular problems and facial features (which, while common, are not always present).

Some diagnostic studies suggest that reliance on facial features to identify Williams syndrome may cause a misdiagnosis of the condition. Among the more reliable features suggestive of Williams are congenital heart disease, periorbital fullness ("puffy" eyes), and the presence of a long smooth philtrum. Less reliable signs of the syndrome include anteverted nostrils, a wide mouth, and an elongated neck. Researchers indicate that even with significant clinical experience, it is difficult to reliably identify Williams syndrome based on facial features alone.

Prenatal Diagnosis:

- Aymé, "et al." (1989) reported prenatal diagnosis of Fryns syndrome by sonography between 24 and 27 weeks.

- Manouvrier-Hanu et al. (1996) described the prenatal diagnosis of Fryns syndrome by ultrasonographic detection of diaphragmatic hernia and cystic hygroma. The diagnosis was confirmed after termination of the pregnancy. The fetus also had 2 erupted incisors; natal teeth had not been mentioned in other cases of Fryns syndrome.

Differential Diagnosis:

- McPherson et al. (1993) noted the phenotypic overlap between Fryns syndrome and the Pallister–Killian syndrome (601803), which is a dysmorphic syndrome with tissue-specific mosaicism of tetrasomy 12p.

- Veldman et al. (2002) discussed the differentiation between Fryns syndrome and Pallister–Killian syndrome, noting that differentiation is important to genetic counseling because Fryns syndrome is an autosomal recessive disorder and Pallister–Killian syndrome is usually a sporadic chromosomal aberration. However, discrimination may be difficult due to the phenotypic similarity. In fact, in some infants with 'coarse face,' acral hypoplasia, and internal anomalies, the initial diagnosis of Fryns syndrome had to be changed because mosaicism of isochromosome 12p was detected in fibroblast cultures or kidney tissue. Although congenital diaphragmatic hernia is a common finding in both syndromes, bilateral congenital diaphragmatic hernia had been reported only in patients with Fryns syndrome until the report of the patient with Pallister–Killian syndrome by Veldman et al. (2002).

- Slavotinek (2004) reviewed the phenotypes of 52 reported cases of Fryns syndrome and reevaluated the diagnostic guidelines. She concluded that congenital diaphragmatic hernia and distal limb hypoplasia are strongly suggestive of Fryns syndrome, with other diagnostically relevant findings including pulmonary hypoplasia, craniofacial dysmorphism, polyhydramnios, and orofacial clefting. Slavotinek (2004) stated that other distinctive anomalies not mentioned in previous guidelines include ventricular dilatation or hydrocephalus, agenesis of the corpus callosum, abnormalities of the aorta, dilatation of the ureters, proximal thumbs, and broad clavicles.

The diagnosis of Perlman syndrome is based on observed phenotypic features and confirmed by histological examination of the kidneys. Prenatal diagnosis is possible for families that have a genetic disposition for Perlman syndrome although there is no conclusive laboratory test to confirm the diagnosis. Fetal overgrowth, particularly with an occipitofrontal circumference (OFC) greater than the 90th centile for gestational age, as well as an excess of amniotic fluid in the amniotic sac (polyhydramnios), may be the first signs of Perlman. Using ultrasound diagnosis, Perlman syndrome has been detected at 18 weeks. During the first trimester, the common abnormalities of the syndrome observed by ultrasound include cystic hygroma and a thickened nuchal lucency. Common findings for the second and third trimesters include macrosomia, enlarged kidneys, renal tumors (both hamartoma and Wilms), cardiac abnormalities and visceromegaly.

Prompt recognition and identification of the disorder along with accurate follow-up and clinical assistance is recommended as the prognosis for Perlman is severe and associated with a high neonatal death rate.

Treatment of Aicardi syndrome primarily involves management of seizures and early/continuing intervention programs for developmental delays.

Additional comorbidities and complications sometimes seen with Aicardi syndrome include porencephalic cysts and hydrocephalus, and gastro-intestinal problems. Treatment for porencephalic cysts and/or hydrocephalus is often via a shunt or endoscopic of the cysts, though some require no treatment. Placement of a feeding tube, fundoplication, and surgeries to correct hernias or other gastrointestinal structural problems are sometimes used to treat gastro-intestinal issues.

Aicardi syndrome is typically characterized by the following triad of features - however, one of the "classic" features being missing does not preclude a diagnosis of Aicardi Syndrome, if other supporting features are present.

1. Partial or complete absence of the corpus callosum in the brain (agenesis of the corpus callosum);

2. Eye abnormalities known as "lacunae" of the retina that are quite specific to this disorder; [optic nerve coloboma]]; and

3. The development in infancy of seizures that are called infantile spasms.

Other types of defects of the brain such as microcephaly, polymicrogyria, porencephalic cysts and enlarged cerebral ventricles due to hydrocephalus are also common in Aicardi syndrome.

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.

Syndactyly and other deformities are typically observed and diagnosed at birth. Long QT syndrome sometimes presents itself as a complication due to surgery to correct syndactyly. Other times, children collapse spontaneously while playing. In all cases it is confirmed with ECG measurements. Sequencing of the CACNA1C gene further confirms the diagnosis.

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.

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.

There is no cure for Williams syndrome. Suggestions include avoidance of extra calcium and vitamin D, as well as treating high levels of blood calcium. Blood vessel narrowing can be a significant health problem, and is treated on an individual basis.

Physical therapy is helpful to patients with joint stiffness and low muscle tone. Developmental and speech therapy can also help children and increase the success of their social interactions. Other treatments are based on a patient's particular symptoms.

The American Academy of Pediatrics recommends annual cardiology evaluations for individuals with Williams syndrome. Other recommended assessments include: ophthalmologic evaluations, an examination for inguinal hernia, objective hearing assessment, blood pressure measurement, developmental and growth evaluation, orthopedic assessments on joints, muscle tone, and ongoing feeding and dietary assessments to manage constipation and urinary problems.

Behavioral treatments have been shown to be effective. In regards to social skills it may be effective to channel their nature by teaching basic skills. Some of these are the appropriate way to approach someone, how and when to socialize in settings such as school or the workplace, and warning of the signs and dangers of exploitation. For the fear that they demonstrate cognitive-behavioral approaches, such as therapy, are the recommended treatment. One of the things to be careful of with this approach is to make sure that the patients' charming nature does not mask any underlying feelings.

Perhaps the most effective treatment for those with Williams syndrome is music. Those with Williams syndrome have shown a relative strength in regards to music, albeit only in pitch and rhythm tasks. Not only do they show a strength in the field but also a particular fondness for it. It has been shown that music may help with the internal and external anxiety that these people are more likely to be afflicted with. Something of note is that the typical person processes music in the superior temporal and middle temporal gyri. Those with Williams syndrome have a reduced activation in these areas but an increase in the right amygdala and cerebellum.

People affected by Williams syndrome are supported by multiple organizations, including the Canadian Association for Williams Syndrome and the Williams Syndrome Registry.

Perlman syndrome shares clinical overlaps with other overgrowth disorders, with similarities to Beckwith–Wiedemann syndrome and Simpson-Golabi-Behmel syndrome having been particularly emphasized in scientific study. Similarities with Beckwith-Wiedemann syndrome include polyhydramnios, macrosomia, nephromegaly and hypoglycaemia. It is the distinctive facial dysmorphology of Perlman, including deep-set eyes, depressed nasal bridge, everted upper lip, and macrocephaly which allows the two conditions to be distinguished from one another. Diagnosis of Perlman syndrome also overlaps with other disorders associated with Wilms tumor, namely, Sotos syndrome and Weaver syndrome.

Turner syndrome may be diagnosed by amniocentesis or chorionic villus sampling during pregnancy.

Usually, fetuses with Turner syndrome can be identified by abnormal ultrasound findings ("i.e.", heart defect, kidney abnormality, cystic hygroma, ascites). In a study of 19 European registries, 67.2% of prenatally diagnosed cases of Turner Syndrome were detected by abnormalities on ultrasound. 69.1% of cases had one anomaly present, and 30.9% had two or more anomalies.

An increased risk of Turner syndrome may also be indicated by abnormal triple or quadruple maternal serum screen. The fetuses diagnosed through positive maternal serum screening are more often found to

have a mosaic karyotype than those diagnosed based on ultrasonographic abnormalities, and

conversely, those with mosaic karyotypes are less likely to have associated ultrasound abnormalities.

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.

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.

If a contracture is less than 30 degrees, it may not interfere with normal functioning. The common treatment is splinting and occupational therapy. Surgery is the last option for most cases as the result may not be satisfactory.

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.

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.

Turner syndrome can be diagnosed postnatally at any age. Often, it is diagnosed at birth due to heart problems, an unusually wide neck or swelling of the hands and feet. However, it is also common for it to go undiagnosed for several years, typically until the girl reaches the age of puberty/adolescence and she fails to develop properly (the changes associated with puberty do not occur). In childhood, a short stature can be indicative of Turner syndrome.

A test called a karyotype, also known as a chromosome analysis, analyzes the chromosomal composition of the individual. This is the test of choice to diagnose Turner syndrome.

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.