Diagnosing Jacobsen Syndrome can be difficult in some cases because it is a rare chromosomal disorder. There are a variety of tests that can be carried out like karyotype, cardiac echocardiogram, a renal sonogram, a platelet count, blood count, a brain imaging study. Genetic testing can be carried out for diagnosis. In which chromosomes are stained to give a barcode like appearance and studied under the microscope which reveals the broken and deleted genes. It can also be diagnosed early in the prenatal stage if there are any abnormalities seen in the ultrasound. A simple assessment of the symptoms can be done to diagnose the Syndrome. A thorough physical examination could be carried out to assess the symptoms.

1. Clinical Genetics and Genetic Testing

Genetic testing is necessary to confirm the diagnosis of PMS. A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small to detect with this method. Chromosomal microarray should be ordered in children with suspected developmental delays or ASD. Most cases will be identified by microarray; however, small variations in genes might be missed. The falling cost for whole exome sequencing may replace DNA microarray technology for candidate gene evaluation. Biological parents should be tested with fluorescence "in situ" hybridization (FISH) to rule out balanced translocations or inversions. Balanced translocation in a parent increases the risk for recurrence and heritability within families (figure 3).

Clinical genetic evaluations and dysmorphology exams should be done to evaluate growth, pubertal development, dysmorphic features (table 1) and screen for organ defects (table 2)

2. Cognitive and Behavioral Assessment

All patients should undergo comprehensive developmental, cognitive and behavioral assessments by clinicians with experience in developmental disorders. Cognitive evaluation should be tailored for individuals with significant language and developmental delays. All patients should be referred for specialized speech/language, occupational and physical therapy evaluations.

3. Neurological Management

Individuals with PMS should be followed by a pediatric neurologist regularly to monitor motor development, coordination and gait, as well as conditions that might be associated with hypotonia. Head circumference should be performed routinely up until 36 months. Given the high rate of seizure disorders (up to 41% of patients) reported in the literature in patients with PMS and its overall negative impact on development, an overnight video EEG should be considered early to rule out seizure activity. In addition, a baseline structural brain MRI should be considered to rule out the presence of structural abnormalities.

4. Nephrology

All patients should have a baseline renal and bladder ultrasonography and a voiding cystourethrogram should be considered to rule out structural and functional abnormalities. Renal abnormalities are reported in up to 38% of patients with PMS. Vesicouretral reflux, hydronephrosis, renal agenesis, dysplasic kidney, polycystic kidney and recurrent urinary tract infections have all been reported in patients with PMS.

5. Cardiology

Congenital heart defects (CHD) are reported in samples of children with PMS with varying frequency (up to 25%)(29,36). The most common CHD include tricuspid valve regurgitation, atrial septal defects and patent ductus arteriousus. Cardiac evaluation, including echocardiography and electrocardiogram, should be considered.

6. Gastroenterology

Gastrointestinal symptoms are common in individuals with PMS. Gastroesophageal reflux, constipation, diarrhea and cyclic vomiting are frequently described.

Table 3: Clinical Assessment Recommendations in Phelan McDermid Syndrome.

Diagnosis is achieved by examining the structure of the chromosomes through karyotyping; while once born, one can do the following to ascertain a diagnosis of the condition:

- MRI

- EEG

Ring chromosome 14 syndrome is extremely rare, the true rate of occurrence is unknown (as it is "less than" 1 per 1,000,000), but there are at least 50 documented cases in the literature.

Diagnosis of 22q11.2 deletion syndrome can be difficult due to the number of potential symptoms and the variation in phenotypes between individuals. It is suspected in patients with one or more signs of the deletion. In these cases a diagnosis of 22q11.2DS is confirmed by observation of a deletion of part of the long arm (q) of chromosome 22, region 1, band 1, sub-band 2. Genetic analysis is normally performed using fluorescence "in situ" hybridization (FISH), which is able to detect microdeletions that standard karyotyping (e.g. G-banding) miss. Newer methods of analysis include Multiplex ligation-dependent probe amplification assay (MLPA) and quantitative polymerase chain reaction (qPCR), both of which can detect atypical deletions in 22q11.2 that are not detected by FISH. qPCR analysis is also quicker than FISH, which can have a turn around of 3 to 14 days.

A 2008 study of a new high-definition MLPA probe developed to detect copy number variation at 37 points on chromosome 22q found it to be as reliable as FISH in detecting normal 22q11.2 deletions. It was also able to detect smaller atypical deletions that are easily missed using FISH. These factors, along with the lower expense and easier testing mean that this MLPA probe could replace FISH in clinical testing.

Genetic testing using BACs-on-Beads has been successful in detecting deletions consistent with 22q11.2DS during prenatal testing. Array-comparative genomic hybridization (array-CGH) uses a large number of probes embossed in a chip to screen the entire genome for deletions or duplications. It can be used in post and pre-natal diagnosis of 22q11.2.

Fewer than 5% of individuals with clinical symptoms of the 22q11.2 deletion syndrome have normal routine cytogenetic studies and negative FISH testing. In these cases, atypical deletions are the cause. Some cases of 22q11.2 deletion syndrome have defects in other chromosomes, notably a deletion in chromosome region 10p14.

Suspicion of a chromosome abnormality is typically raised due to the presence of developmental delays or birth defects. Diagnosis of ring 18 is usually made via a blood sample. A routine chromosome analysis, or karyotype, is usually used to make the initial diagnosis, although it may also be made by microarray analysis. Increasingly, microarray analysis is also being used to clarify breakpoints. Prenatal diagnosis is possible via amniocentesis or chorionic villus sampling.

Prenatal screening is not typically done for FHM, however it may be performed if requested. As penetrance is high, individuals found to carry mutations should be expected to develop signs of FHM at some point in life.

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)

After the first discovery and description of Marshall–Smith syndrome in 1971, research to this rare syndrome has been carried out.

- Adam, M., Hennekam, R.C.M., Butler, M.G., Raf, M., Keppen, L., Bull, M., Clericuzio, C., Burke, L., Guttacher, A., Ormond, K., & Hoyme, H.E. (2002). Marshall–Smith syndrome: An osteochondrodysplasia with connective tissue abnormalities. 23rd Annual David W. Smith Workshop on Malformations and Morphogenesis, August 7, Clemson, SC.

- Adam MP, Hennekam RC, Keppen LD, Bull MJ, Clericuzio CL, Burke LW, Guttmacher AE, Ormond KE and Hoyme HE: Marshall-Smith Syndrome: Natural history and evidence of an osteochondrodysplasia with connective tissue abnormalities. American Journal of Medical Genetics 137A:117–124, 2005.

- Baldellou Vazquez A, Ruiz-Echarri Zelaya MP, Loris Pablo C, Ferr#{225}ndez Longas A, Tamparillas Salvador M. El sIndrome de Marshall-Smith: a prop#{243}sito de una observad#{243}n personal. An Esp Pediatr 1983; 18:45-50.

- Butler, M.G. (2003). Marshall–Smith syndrome. In: The NORD Guide to Rare Disorders. (pp219–220) Lippincott, Williams & Wilkins, Philadelphia, PA.

- Charon A, Gillerot T, Van Maldergem L, Van Schaftingen MH, de Bont B, Koulischer L. The Marshall–Smith syndrome. Eur J Pediatr 1990; 150: 54-5.

- Dernedde, G., Pendeville, P., Veyckemans, F., Verellen, G. & Gillerot, Y. (1998). Anaesthetic management of a child with Marshall–Smith syndrome. Canadian Journal of Anesthesia. 45 (7): 660. Anaesthetic management of a child with Marshall-Smith syndrome

- Diab, M., Raff, M., Gunther, D.F. (2002). Osseous fragility in Marshall–Smith syndrome. Clinical Report: Osseous fragility in Marshall-Smith syndrome

- Ehresmann, T., Gillessen-Kaesbach G., Koenig R. (2005). Late diagnosis of Marshall Smith Syndrome (MSS). In: Medgen 17.

- Hassan M, Sutton T, Mage K, LimalJM, Rappaport R. The syndrome of accelerated bone maturation in the newborn infant with dysmorphism and congenital malformations: (the so-called Marshall–Smith syndrome). Pediatr Radiol 1976; 5:53-57.

- Hoyme HE and Bull MJ: The Marshall-Smith Syndrome: Natural history beyond infancy. Western Society for Pediatric Research, Carmel, California, February, 1987. Clin Res 35:68A, 1987.

- Hoyme HE and Bull MJ: The Marshall-Smith Syndrome: Natural history beyond infancy. David W. Smith Morphogenesis and Malformations Workshop. Greenville, SC, August, 1987. Proceedings of the Greenwood Genetics Center 7:152, 1988.

- Hoyme HE, Byers PH, Guttmacher AE: Marshall–Smith syndrome: Further evidence of an osteochondrodysplasia in long-term survivors. David W. Smith Morphogenesis and Malformations Workshop, Winston-Salem, NC, August, 1992. Proceedings of the Greenwood Genetic Center 12:70, 1993.

- .

- Tzu-Jou Wang (2002). Marshall–Smith syndrome in a Taiwanese patient with T-cell immunodeficiency. Am J Med Genet Part A;112 (1):107-108.

At present, treatment for ring 18 is symptomatic, meaning that the focus is on treating the signs and symptoms of the conditions as they arise. To ensure early diagnosis and treatment, it is suggested that people with ring 18 undergo routine screenings for thyroid, hearing, and vision problems.

There has been no treatment discovered for Jacobsen Syndrome until now but the Symptoms can be treated. 56% of children with Jacobsen Syndrome have congenital heart problems to keep them in check a baseline evaluation can be made by a paediatric cardiologist by carrying out an electrocardiogram or echocardiogram. Any problems that are found can be treated then.

Almost all affected children are born with a bleeding disorder, monthly CBT may help ease the problem. Consecutively Platelet transfusion and ddAVP can be carried out. Medication that interferes with platelet count should be avoided and oral contraceptive therapy may be considered for women with heavy bleeding during menses.

Children affected with Jacobsen Syndrome have severe to Moderate intellectual disabilities and cognitive impairment. An evaluation by a neuropsychologist or a behaviour specialist like a Psychiatrist or Psychologist can be performed, including brain imaging like MRI or ERP. Then as deemed appropriate intervention programs can be carried through. Music therapy is very beneficial for language development. According to the age, befitting vision and hearing test can aid in fixing problems related cognition. For problems related to behaviour like ADHD, medication or therapy would be required but a combination of both is more effective. An ophthalmologist should be consulted to treat the eye defects. Play and interactive games encourage the child to speak. Habilitiation in children should begin at an early age. A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. The entire family is supported to help the affected children and their families adjust better.

Most affected people have a stable clinical course but are often transfusion dependent.

22q11.2 deletion syndrome was estimated to affect between one in 2000 and one in 4000 live births. This estimate is based on major birth defects and may be an underestimate, because some individuals with the deletion have few symptoms and may not have been formally diagnosed. It is one of the most common causes of mental retardation due to a genetic deletion syndrome.

The prevalence of 22q11.2DS has been expected to rise because of multiple reasons: (1) Thanks to surgical and medical advances, an increasing number of people are surviving heart defects associated with the syndrome. These individuals are in turn having children. The chances of a 22q11.2DS patient having an affected child is 50% for each pregnancy; (2) Parents who have affected children, but who were unaware of their own genetic conditions, are now being diagnosed as genetic testing become available; (3) Molecular genetics techniques such as FISH (fluorescence in situ hybridization) have limitations and have not been able to detect all 22q11.2 deletions. Newer technologies have been able to detect these atypical deletions.

Recently, the syndrome has been estimated to affect up to one in 2000 live births. Testing for 22q11.2DS in over 9500 pregnancies revealed a prevalence rate of 1/992.

The true prevalence of PMS has not been determined. More than 1200 people have been identified worldwide according the Phelan-McDermid Syndrome Foundation. However, it is believed to be underdiagnosed due to inadequate genetic testing and lack of specific clinical features. It is known to occur with equal frequency in males and females. Studies using chromosomal microarray for diagnosis indicate that at least 0.5% of cases of ASD can be explained by mutations or deletions in the "SHANK3" gene. In addition when ASD is associated with ID, "SHANK3" mutations or deletions have been found in up to 2% of individuals.

Diagnosis of FHM is made according to the following criteria:

- Two attacks of each of the following:

- At least one close (first or second degree) relative with FHM

- No other likely cause

Sporadic forms follow the same diagnostic criteria, with the exception of family history.

In all cases, family and patient history is used for diagnosis. Brain imaging techniques, such as MRI, CAT scans and SPECT, are used to look for signs of other familial conditions such as CADASIL or mitochondrial disease, and for evidence of cerebellar degeneration. With the discovery of causative genes, genetic sequencing can also be used to verify diagnosis (though not all genetic loci are known).

The abnormalities common to cat eye syndrome were first cataloged in 1899. It was described in association with a small marker chromosome in 1965. Early reports of cat eye syndrome discuss the possibility of chromosome 13 involvement. Now, CES is considered to be present with the chromosome 22 trisomy findings.

The additional chromosome 22 usually arises spontaneously. It may be hereditary and parents may be mosaic for the marker chromosome but show no phenotypic symptoms of the syndrome.

The chromosomal area included in the cat eye syndrome "critical region" is 22pter→q11.

The diagnosis is made on the basis of clinical parameters, the peripheral blood smear, and low immunoglobulin levels. Typically, IgM levels are low, IgA levels are elevated, and IgE levels may be elevated; paraproteins are occasionally observed. Skin immunologic testing (allergy testing) may reveal hyposensitivity. Not all patients have a positive family history of the disorder; new mutations do occur. Often, leukemia may be suspected on the basis of low platelets and infections, and bone marrow biopsy may be performed. Decreased levels of Wiskott-Aldrich syndrome protein and/or confirmation of a causative mutation provides the most definitive diagnosis.

Sequence analysis can detect the WAS-related disorders of Wiskott–Aldrich syndrome, XLT, and XLN. Sequence analysis of the "WASp" gene can detect about 98% of mutations in males and 97% of mutations in female carriers. Because XLT and XLN symptoms may be less severe than full WAS and because female carriers are usually asymptomatic, clinical diagnosis can be elusive. In these cases, genetic testing can be instrumental in diagnosis of WAS-related disorders.

Lenalidomide has activity in 5q- syndrome and is FDA approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndrome (MDS) associated with chromosome 5q deletion with or without additional cytogenetic abnormalities. There are several possible mechanisms that link the haploinsufficiency molecular lesions with lenalidomide sensitivity.

Treatment for NPS varies depending on the symptoms observed.

- Perform screening for renal disease and glaucoma, surgery, intensive physiotherapy, or genetic counseling.

- ACE inhibitors are taken to treat proteinuria and hypertension in NPS patients.

- Dialysis and renal transplant.

- Physical therapy, bracing and analgesics for joint pain.

- Other surgery treatments such as patella realignment, joint replacement, and the cutting away of the head of radius.

This includes Chediak-Higashi syndrome and Elejalde syndrome (neuroectodermal melanolysosomal disease).

Distal trisomy 10 is a rare chromosomal disorder that causes several physical defects and intellectual disability.

Humans, like all sexually reproducing species, have somatic cells that are in diploid [2N] state, meaning that N represent the number of chromosomes, and 2 the number of their copies. In humans, there are 23 chromosomes, but there are two sets of them, one from mother and one from father, totaling in 46, that are arranged according to their size, function and genes they carry. Each cell is supposed to have two of each, but sometimes due to mutations or malfunctions during cell division, mistakes are made that cause serious health problems. One such error is the cause of Distal trisomy 10q disorder.

Each chromosome has two arms, labeled p (for petite, or short) and q (for long). If both arms are equal in length, the chromosome is said to be metacentric. If arms' lengths are unequal, chromosome is said to be submetacentric, and if p arm is so short that is hard to observe, but still present, then the chromosome is acrocentric. In Distal Trisomy 10q disorder, end or distal portion of the q (long) arm of the chromosome number 10 appears to be present three times, rather than two times as it is supposed to be. This extra arm results in chromosome 10 trisomy, meaning that three arms are present. Depending on the length of the aberrant arm, the severity can vary from case to case. Often the source of this chromosomal error is a translocation in one of the parents. Sometimes it occurs spontaneously, in which case it is termed "de novo".

This syndrome has a large range of outcomes depending on how much chromosomal material is involved. Outcomes include: very slow postnatal growth, hypotonia, lack of coordination skills and mild to severe cases of intellectual disability, digestive issues, and heart and kidney problems. Individuals with this disorder can also be distinguished by their facial features. Number of support groups do exist in the United States, where affected families can meet and discuss problems they encounter, possible treatments and can find emotional support.

The diagnosis of immunodysregulation polyendocrinopathy enteropathy X-linked syndrome is consistent with the following criteria:

- Clinical examination

- Family history

- Laboratory findings

- Genetic testing

Jin et al. (2004) employ a numerical grading of severity:

- 0.5: intermittent thrombocytopenia

- 1.0: thrombocytopenia and small platelets (microthrombocytopenia)

- 2.0: microthrombocytopenia plus normally responsive eczema or occasional upper respiratory tract infections

- 2.5: microthrombocytopenia plus therapy-responsive but severe eczema or airway infections requiring antibiotics

- 3.0: microthrombocytopenia plus both eczema and airway infections requiring antibiotics

- 4.0: microthrombocytopenia plus eczema continuously requiring therapy and/or severe or life-threatening infections

- 5.0: microthrombocytopenia plus autoimmune disease or malignancy

Chromosome 15q trisomy is an extremely rare genetic disorder, caused by a chromosomal aberration in which there is an excess copy of the long ("q") arm of human chromosome 15. The disorder is also known as Distal Duplication 15q and Partial Duplication 15q Syndrome.

The disorder is primarily characterized by growth abnormalities, which range from growth retardation to accelerated growth, intellectual disability, and distinctive malformations of the head and face. Additional abnormalities may involve malformation of the skeleton, spine and neck; fingers and/or toes; genitals (particularly in males); and, in some cases, heart problems. When accelerated growth is present, it is thought to result from the duplication of the IGF1 receptor gene.