When accompanied by the combination of situs inversus (reversal of the internal organs), chronic sinusitis, and bronchiectasis, it is known as Kartagener syndrome (only 50% of primary ciliary dyskinesia cases include situs inversus).

The diagnosis of nephronophthisis can be obtained via a renal ultrasound, family history and clinical history of the affected individual according to Stockman, et al.

Prevention for Alström Syndrome is considered to be harder compared to other diseases/syndromes because it is an inherited condition. However, there are other options that are available for parents with a family history of Alström Syndrome. Genetic testing and counseling are available where individuals are able to meet with a genetic counselor to discuss risks of having the children with the disease. The genetic counselor may also help determine whether individuals carry the defective ALSM1 gene before the individuals conceive a child. Some of the tests the genetic counselors perform include chorionic villus sampling (CVS), Preimplantation genetic diagnosis (PGD), and amniocentesis. With PGD, the embryos are tested for the ALSM1 gene and only the embryos that are not affected may be chosen for implantation via in vitro fertilization.

Several diagnostic tests for this condition have been proposed. These include nasal nitric oxide levels, light microscopy of biopsies for ciliary beat pattern and frequency and electron microscopic examination of dynein arms. Genetic testing has also been proposed but this is difficult given that there are multiple genes involved.

It is possible to clinically detect Alström syndrome in infancy, but more frequently, it is detected much later, as doctors tend to detect symptoms as separate problems. Currently, Alström syndrome is often diagnosed clinically, since genetic testing is costly and only available on a limited basis.

A physical examination would be needed to properly diagnose the patient. Certain physical characteristics can determine if the patient has some type of genetic disorder. Usually, a geneticist would perform the physical examination by measuring the distance around the head, distance between the eyes, and the length of arms and legs. In addition, examinations for the nervous system or the eyes may be performed. Various imaging studies like computerized tomography scans (CT), Magnetic Resonance Imaging (MRI), or X-rays are used to see the structures within the body.

Family and personal medical history are required. Information about the health of an individual is crucial because it provides traces to a genetic diagnosis.

Laboratory tests, particularly genetic testing, are performed to diagnose genetic disorders. Some of the types of genetic testing are molecular, biochemical, and chromosomal. Other laboratory tests performed may measure levels of certain substances in urine and blood that can also help suggest a diagnosis.

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.

In a sample of 19 children, a 1997 study found that 3 died before the age of 3, and 2 never learned to walk. The children had various levels of delayed development with developmental quotients from 60 to 85.

The most characteristic biochemical indicator of SLOS is an increased concentration of 7DHC (reduced cholesterol levels are also typical, but appear in other disorders as well). Thus, prenatally, SLOS is diagnosed upon finding an elevated 7DHC:total sterol ratio in fetal tissues, or increased levels of 7DHC in amniotic fluid. The 7DHC:total sterol ratio can be measured at 11–12 weeks of gestation by chorionic villus sampling, and elevated 7DHC in amniotic fluid can be measured by 13 weeks. Furthermore, if parental mutations are known, DNA testing of amniotic fluid or chorionic villus samples may be performed.

Amniocentesis (process of sampling amniotic fluid) and chorionic villus sampling cannot be performed until approximately 3 months into the pregnancy. Given that SLOS is a very severe syndrome, parents may want to choose to terminate their pregnancy if their fetus is affected. Amniocentesis and chorionic villus sampling leave very little time to make this decision (abortions become more difficult as the pregnancy advances), and can also pose severe risks to the mother and baby. Thus, there is a very large desire for noninvasive midgestation diagnostic tests. Examining the concentrations of sterols in maternal urine is one potential way to identify SLOS prenatally. During pregnancy, the fetus is solely responsible for synthesizing the cholesterol needed to produce estriol. A fetus with SLOS cannot produce cholesterol, and may use 7DHC or 8DHC as precursors for estriol instead. This creates 7- or 8-dehydrosteroids (such as 7-dehydroestriol), which may show up in the maternal urine. These are novel metabolites due to the presence of a normally reduced double bond at carbon 7 (caused by the inactivity of DHCR7), and may be used as indicators of SLOS. Other cholesterol derivatives which possess a double bond at the 7th or 8th position and are present in maternal urine may also be indicators of SLOS. 7- and 8-dehydropregnanetriols have been shown to be present in the urine of mothers with an affected fetus but not with an unaffected fetus, and thus are used in diagnosis. These pregnadienes originated in the fetus and traveled through the placenta before reaching the mother. Their excretion indicates that neither the placenta nor the maternal organs have necessary enzymes needed to reduce the double bond of these novel metabolites.

Orofaciodigital syndrome type 1 can be treated with reconstructive surgery or the affected parts of the body. Surgery of cleft palate, tongue nodules, additional teeth, accessory frenulae, and orthodontia for malocclusion. Routine treatment for patients with renal disease and seizures may also be necessary. Speech therapy and special education in the later development may also be used as management.

The management of this condition can be done via-improvement of any electrolyte imbalance, as well as, hypertension and anemia treatment as the individuals condition warrants.

If SLOS goes undetected until after birth, diagnosis may be based on the characteristic physical features as well as finding increased plasma levels of 7DHC.

There are many different ways of detecting 7DHC levels in blood plasma, one way is using the Liebermann–Burchard (LB) reagent. This is a simple colorimetric assay developed with the intention of use for large scale screening. When treated with the LB reagent, SLOS samples turn pink immediately and gradually become blue; normal blood samples are initially colorless and develop a faint blue color. Although this method has limitations and is not used to give a definitive diagnosis, it has appeal in that it is a much faster method than using cell cultures.

Another way of detecting 7DHC is through gas chromatography, a technique used to separate and analyze compounds. Selected ion

monitoring gas chromatography/mass-spectrometry (SIM-GC/MS) is a very sensitive version of gas chromatography, and permits detection of even mild cases of SLOS. Other methods include time-of-flight mass spectrometry, particle-beam LC/MS, electrospray tandem MS, and ultraviolet absorbance, all of which may be used on either blood samples, amniotic fluid, or chorionic villus. Measuring levels of bile acids in patients urine, or studying DCHR7 activity in tissue culture are also common postnatal diagnostic techniques.

It is an autosomal recessive disease.

Sonography shows bilateral small kidneys with loss of corticomedullary junction and multiple cysts only in the medulla. Cysts may only be seen if they are large enough, they are rarely visible early in disease.

Patients with medullary cystic disease present with similar features as juvenile nephronophthisis but they can be differentiated by:

1. Absence of growth retardation.

2. Age of presentation is third or fourth decade.

3. Hypertension may occur (in JN, hypertension is not seen).

In polycystic kidney disease, there is bilateral enlargement of kidneys (small kidneys in JN).

The disorder is characterized by absence or underdevelopment of the cerebellar vermis and a malformed brain stem (molar tooth sign), both of which can be visualized on a MRI scan. Together with this sign, the diagnosis is based on the physical symptoms and genetic testing for mutations. If the gene mutations have been identified in a family member, prenatal or carrier diagnosis can be pursued.

Joubert Syndrome is known to affect 1 in 80,000-100,000 newborns. Due to the variety of genes this disorder is affected by, it is likely to be under-diagnosed. It is commonly found in Ashkenazi Jewish, French-Canadians, and Hutterite ethnic populations. Most cases of Joubert syndrome are autosomal recessive - in these cases, both parents are either carriers or affected. Rarely, Joubert syndrome is inherited in an X-linked recessive pattern. In these cases, males are more commonly affected because affected males must have one X chromosome mutated, while affected females must have mutated genes on both X chromosomes.

Dysplastic kidneys are prevalent in over 95% of all identified cases. When this occurs, microscopic cysts develop within the kidney and slowly destroy it, causing it to enlarge to 10 to 20 times its original size. The level of amniotic fluid within the womb may be significantly altered or remain normal, and a normal level of fluid should not be criteria for exclusion of diagnosis.

Occipital encephalocele is present in 60% to 80% of all cases, and post-axial polydactyly is present in 55% to 75% of the total number of identified cases. Bowing or shortening of the limbs are also common.

Finding at least two of the three phenotypic features of the classical triad, in the presence of normal karyotype, makes the diagnosis solid. Regular ultrasounds and pro-active prenatal care can usually detect symptoms early on in a pregnancy.

Recent research has been focused on studying large series of cases of 3-M syndrome to allow scientists to obtain more information behind the genes involved in the development of this disorder. Knowing more about the underlying mechanism can reveal new possibilities for treatment and prevention of genetic disorders like 3-M syndrome.

- One study looks at 33 cases of 3M syndrome, 23 of these cases were identified as CUL7 mutations: 12 being homozygotes and 11 being heterozygotes. This new research shows genetic heterogeneity in 3M syndrome, in contrast to the clinical homogeneity. Additional studies are still ongoing and will lead to the understanding of this new information.

- This study provides more insight on the three genes involved in 3M syndrome and how they interact with each other in normal development. It lead to the discovery that the CUL7, OBS1, and CCDC8 form a complex that functions to maintain microtubule and genomic integrity.

While not precisely known, it is estimated that the general rate of incidence, according to Bergsma, for Meckel syndrome is 0.02 per 10,000 births. According to another study done six years later, the incidence rate could vary from 0.07 to 0.7 per 10,000 births.

This syndrome is a Finnish heritage disease. Its frequency is much higher in Finland, where the incidence is as high as 1.1 per 10,000 births. It is estimated that Meckel syndrome accounts for 5% of all neural tube defects there.

It is the most common genetic cause of end stage renal disease (renal failure) in childhood and adolescence.

There is no causative / curative therapy. Symptomatic medical treatments are focussing on symptoms caused by orthopaedic, dental or cardiac problems. Regarding perioperative / anesthesiological management, recommendations for medical professionals are published at OrphanAnesthesia.

Treatment of 3-M syndrome is aimed at the specific symptoms presented in each individual. With the various symptoms of this disorder being properly managed and affected individuals having normal mental development, 3-M syndrome is not a life - threatening condition and individuals are able to lead a near normal life with normal life expectancy.

Treatment may involve the coordinated efforts of many healthcare professionals, such as pediatricians, orthopedists, dentists and/or other specialists depending on the symptoms.

- Possible management options for short stature are surgical bone lengthening or growth hormone therapy.

- Orthopedic techniques and surgery may be used to treat certain skeletal abnormalities.

- Plastic surgery may also be performed on individuals to help correct certain cranio-facial anomalies.

- Individuals with dental abnormalities may undergo corrective procedures such as braces or oral surgeries.

"The phenotypic parameters that define a ciliopathy may be used to both recognize the cellular basis of a number of genetic disorders and to facilitate the diagnosis and treatment of some diseases of unknown" cause.

The caloric intake of children with SRS must be carefully controlled in order to provide the best opportunity for growth. If the child is unable to tolerate oral feeding, then enteral feeding may be used, such as the percutaneous endoscopic gastrostomy.

In children with limb-length differences or scoliosis, physiotherapy can alleviate the problems caused by these symptoms. In more severe cases, surgery to lengthen limbs may be required. To prevent aggravating posture difficulties children with leg length differences may require a raise in their shoe.

Growth hormone therapy is often prescribed as part of the treatment of SRS. The hormones are given by injection typically daily from the age of 2 years old through teenage years. It may be effective even when the patient does not have a growth hormone deficiency. Growth hormone therapy has been shown to increase the rate of growth in patients and consequently prompts 'catch up' growth. This may enable the child to begin their education at a normal height, improving their self-esteem and interaction with other children. The effect of growth hormone therapy on mature and final height is as yet uncertain. There are some theories suggesting that the therapy also assists with muscular development and managing hypoglycemia.

Respiratory complications are often cause of death in early infancy.

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)

Vestronidase alfa-vjbk (Mepsevii) is the only drug approved by U.S. Food and Drug Administration for the treatment of pediatric and adult patients.

Raine syndrome (RNS), also called osteosclerotic bone dysplasia, is a rare autosomal recessive congenital disorder characterized by craniofacial anomalies including microcephaly, noticeably low set ears, osteosclerosis, a cleft palate, gum hyperplasia, a hypoplastic nose, and eye proptosis. It is considered to be a lethal disease, and usually leads to death within a few hours of birth. However, a recent report describes two studies in which children with Raine Syndrome have lived to 8 and 11 years old, so it is currently proposed that there is a milder expression that the phenotype can take (Simpson 2009).

It was first characterized in 1989 in a report that was published on an infant that had been born with an unknown syndrome, that later came to be called Raine Syndrome.

The current research describes Raine Syndrome as a neonatal osteosclerotic bone dysplasia, indicated by its osteosclerotic symptoms that are seen in those suffering from the disease. It has been found that a mutation in the gene FAM20C is the cause of the Raine Syndrome phenotype. This microdeletion mutation leads to an unusual chromosome 7 arrangement. The milder phenotypes of Raine Syndrome, such as those described in Simpson’s 2007 report, suggest that Raine Syndrome resulting from missense mutations may not be as lethal as the other described mutations (OMIM). This is supported by findings from Fradin et al. (2011), who reported on children with missense mutations to FAM20C and lived to ages 1 and 4 years, relatively much longer than the life spans of the previously reported children. Simpson et al.’s (2007) report states that to date, effected individuals have had chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion. They had abnormal chromosome 7 arrangements, with microdeletions of their D7S2477 and D7S1484 markers (Simpson 2007).

Raine Syndrome appears to be an autosomal recessive disease. There are reports of recurrence in children born of the same parents, and an increased occurrence in children of closely related, genetically similar parents. Individuals with Raine Syndrome were either homozygous or compound heterozygous for the mutation of FAM20C. Also observed have been nonsynonomous mutation and splice-site changes (Simpson et al. 2007).

FAM20C, located on chromosome 7p22.3, is an important molecule in bone development. Studies in mice have demonstrated its importance in the mineralization of bones in teeth in early development (OMIM, Simpson et al. 2007, Wang et al. 2010). FAM20C stands for “family with sequence similarity 20, member C.” It is also commonly referred to as DMP-4. It is a Golgi-enriched fraction casein kinase and an extracellular serine/threonine protein kinase. It is 107,743 bases long, with 10 exons and 584 amino acids (Weizmann Institute of Science).