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.

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

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.

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.

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.

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.

Microlissencephaly can be diagnosed by prenatal MRI. MRI is better than ultrasound when it comes to detecting microlissencephaly or MSGP prenatally.

The ideal time for proper prenatal diagnosis is between the 34th and 35th gestational week which is the time when the secondary gyration normally terminates. In microlissencephaly cases, the primary sulci would be unusually wide and flat while secondary sulci would be missing.

At birth, lissencephaly with a head circumference of less than minus three standard deviations (< –3 SD) is considered microlissencephaly.

Although genetic diagnosis in patients with MLIS is challenging, exome sequencing has been suggested to be a powerful diagnostic tool.

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.

Once the diagnosis of polymicrogyria has been established in an individual, the following approach can be used for discussion of prognosis:

A pregnancy history should be sought, with particular regard to infections, trauma, multiple gestations, and other documented problems. Screening for the common congenital infections associated with polymicrogyria with standard TORCH testing may be appropriate. Other specific tests targeting individual neurometabolic disorders can be obtained if clinically suggested.

The following may help in determining a genetic etiology:

Family history

It is important to ask for the presence of neurologic problems in family members, including seizures, cognitive delay, motor impairment, pseudobulbar signs, and focal weakness because many affected family members, particularly those who are older, may not have had MRI performed, even if these problems came to medical attention. In addition, although most individuals with polymicrogyria do present with neurologic difficulties in infancy, childhood, or adulthood, those with mild forms may have no obvious deficit or only minor manifestations, such as a simple lisp or isolated learning disability. Therefore, if a familial polymicrogyria syndrome is suspected, it may be reasonable to perform MRI on relatives who are asymptomatic or have what appear to be minor findings. The presence of consanguinity in a child's parents may suggest an autosomal recessive familial polymicrogyria syndrome.

Physical examination

A general physical examination of the proband may identify associated craniofacial, musculoskeletal, or visceral malformations that could indicate a particular syndrome. Neurologic examination should assess cognitive and mental abilities, cranial nerve function, motor function, deep tendon reflexes, sensory function, coordination, and gait (if appropriate).

Genetic testing

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 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.

Microlissencephaly is considered a more severe form than microcephaly with simplified gyral pattern. Microlissencephaly is characterized by a smooth cortical surface (absent sulci and gyri) with a thickened cortex (> 3 mm) and is usually associated with other congenital anomalies. Microcephaly with a simplified gyral pattern has too few sulci and normal cortical thickness (3 mm) and is usually an isolated anomaly.

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.

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.

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.

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.

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.

Parents of a proband

- The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.

- Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

- At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

- Once an at-risk sibling is known to be unaffected, the risk of his/her being a carrier is 2/3.

- Heterozygotes (carriers) are asymptomatic.

Offspring of a proband

- Offspring of a proband are obligate heterozygotes and will therefore carry one mutant allele.

- In populations with a high rate of consanguinity, the offspring of a person with GPR56-related BFPP and a reproductive partner who is a carrier of GPR56-related BFPP have a 50% chance of inheriting two GPR56 disease-causing alleles and having BFPP and a 50% chance of being carriers.

Other family members of a proband.

- Each sibling of the proband's parents is at a 50% risk of being a carrier

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.

The prognosis for patients diagnosed with Timothy syndrome is very poor. Of 17 children analyzed in one study, 10 died at an average age of 2.5 years. Of those that did survive, 3 were diagnosed with autism, one with an autism spectrum disorder, and the last had severe delays in language development. One patient with atypical Timothy syndrome was largely normal with the exception of heart arrhythmia. Likewise, the mother of two Timothy syndrome patients also carried the mutation but lacked any obvious phenotype. In both of these cases, however, the lack of severity of the disorder was due to mosaicism.

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.

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.

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.

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.