MRI will help with the diagnosis of structural abnormality of the brain. Genetic testing may also be pursued.

The diagnosis is based on observing the patient and finding the constellation of symptoms and signs described above. A few blood tests help, by showing signs of long standing inflammation. There is no specific test for the disease, though now that the gene that causes the disease is known, that may change.

Routine laboratory investigations are non specific: anaemia, increased numbers of polymorphs, an elevated erythrocyte sedimentation rate and elevated concentrations of C-reactive protein are typically all the abnormalities found. Lumbar puncture shows elevated levels of polymorphs (20-70% of cases) and occasionally raised eosinophil counts (0-30% of cases). CSF neopterin may be elevated.

The X ray changes are unique and charactistic of this syndrome. These changes include bony overgrowth due to premature ossification of the patella and the long bone epiphyses in very young children and bowing of long bones with widening and shortening periosteal reaction in older ones.

Audiometry shows a progressive sensineural deafness. Visual examination shows optic atrophy and an increase in the blind spot. CT is usually normal but may show enlargement of the ventricles. MRI with contrast may show enhancement of leptomeninges and cochlea consistent with chronic meningitis. EEG shows is non specific with slow waves and spike discharges.

Polymorphs tend to show increased expression of CD10.

Still's disease does not affect children under 6 months old.

Hyperimmunoglobulin D syndrome in 50% of cases is associated with mevalonate kinase deficiency which can be measured in the leukocytes.

There is no treatment for FTHS, though identification of TKS4 mutation as a causative factor may eventually provide new opportunities for neonatal screening in high-risk families.

The heterogeneity of the Klippel–Feil syndrome has made it difficult to outline the diagnosis as well as the prognosis classes for this disease. Because of this, it has complicated the exact explanation of the genetic cause of the syndrome.

The prognosis for most individuals with KFS is good if the disorder is treated early on and appropriately. Activities that can injure the neck should be avoided, as it may contribute to further damage. Other diseases associated with the syndrome can be fatal if not treated, or if found too late to be treatable.

No treatment is available for most of these disorders. Mannose supplementation relieves the symptoms in PMI-CDG (CDG-Ib) for the most part, even though the hepatic fibrosis may persist. Fucose supplementation has had a partial effect on some SLC35C1-CDG (CDG-IIc or LAD-II) patients.

Neuroimaging, usually with computed tomography (CT/CAT) or magnetic resonance imaging (MRI), is used to exclude any mass lesions. In IIH these scans typically appear to be normal, although small or slit-like ventricles, dilatation and buckling of the optic nerve sheaths and "empty sella sign" (flattening of the pituitary gland due to increased pressure) and enlargement of Meckel's caves may be seen.

An MR venogram is also performed in most cases to exclude the possibility of venous sinus stenosis/obstruction or cerebral venous sinus thrombosis. A contrast-enhanced MRV (ATECO) scan has a high detection rate for abnormal transverse sinus stenoses. These stenoses can be more adequately identified and assessed with catheter cerebral venography and manometry. Buckling of the bilateral optic nerves with increased perineural fluid is also often noted on MRI imaging.

Lumbar puncture is performed to measure the opening pressure, as well as to obtain cerebrospinal fluid (CSF) to exclude alternative diagnoses. If the opening pressure is increased, CSF may be removed for transient relief (see below). The CSF is examined for abnormal cells, infections, antibody levels, the glucose level, and protein levels. By definition, all of these are within their normal limits in IIH. Occasionally, the CSF pressure measurement may be normal despite very suggestive symptoms. This may be attributable to the fact that CSF pressure may fluctuate over the course of the normal day. If the suspicion of problems remains high, it may be necessary to perform more long-term monitoring of the ICP by a pressure catheter.

In utero exposure to cocaine and other street drugs can lead to septo-optic dysplasia.

There are different approaches to non-invasive intracranial pressure measurement, which include ultrasound "time-of-flight" techniques, transcranial Doppler, methods based on acoustic properties of the cranial bones, EEG, MRI, tympanic membrane displacement, oto-acoustic emission, ophthalmodynamometry, ultrasound measurements of optic nerve sheath diameter, and Two-Depth Transorbital Doppler. Most of the approaches are "correlation based". Such approaches can not measure an absolute ICP value in mmHg or other pressure units because of the need for individual patient specific calibration. Calibration needs non-invasive "gold standard" ICP meter which does not exists.

Non-invasive absolute intracranial pressure value meter, based on ultrasonic Two-Depth Transorbital Doppler technology, has been shown to be accurate and precise in clinical settings and prospective clinical studies. Analysis of the 171 simultaneous paired recordings of non-invasive ICP and the "gold standard" invasive CSF pressure on 110 neurological patients and TBI patients showed good accuracy for the non-invasive method as indicated by the low mean systematic error (0.12 mmHg; confidence level (CL) = 0.98). The method also showed high precision as indicated by the low standard deviation (SD) of the random errors

(SD = 2.19 mmHg; CL = 0.98).

This measurement method and technique (the only non-invasive ICP measurement technique which already received EU CE Mark approval) eliminates the main limiting problem of all other non-successful "correlation based" approaches to non-invasive ICP absolute value measurement - the need of calibration to the individual patient.

The prevalence of Klippel–Feil syndrome is unknown due to the fact that there was no study done to determine the true prevalence.

Although the actual occurrence for the KFS syndrome is unknown, it is estimated to occur 1 in 40,000 to 42,000 newborns worldwide. In addition, females seem to be affected slightly more often than males.

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 may be suspected on the basis of the history and examination. To confirm the diagnosis, as well as excluding alternative causes, several investigations are required; more investigations may be performed if the history is not typical or the patient is more likely to have an alternative problem: children, men, the elderly, or women who are not overweight.

A thorough history is essential and should cover family history, diet; drug/toxin exposure social history, including tobacco and alcohol use; and occupational background, with details on whether similar cases exist among coworkers. Treatment of any chronic disease such as pernicious anemia should always be elucidated.

In most cases of nutritional/toxic optic neuropathy, the diagnosis may be obtained via detailed medical history and eye examination. Additionally, supplementary neurological imaging studies, such as MRI or enhanced CT, may be performed if the cause remains unclear.

When the details of the examination and history indicate a familial history of similar ocular or systemic disease, whether or not there is evidence of toxic or nutritional causes for disease, certain genetic tests may be required. Because there are several congenital causes of mitochondrial dysfunction, the patients history, examination, and radiological studies must be examined in order to determine the specific genetic tests required. For example, 90% of cases of Leber’s Hereditary Optic Neuropathy (LHON) are associated with three common mtDNA point mutations (m.3460G>A/MT-ND1, m.11778G>A/MT-ND4, m.14484T>C/MT-ND6) while a wider range of mtDNA mutations (MT-ND1, MT-ND5, MT-ND6; http://www.mitomap.org/) have been associated with overlapping phenotypes of LHON, MELAS, and Leigh syndrome.

The treatment, and therefore prognosis, varies depending upon the underlying tumour.

Molecular (DNA) testing for PAX6 gene mutations (by sequencing of the entire coding region and deletion/duplication analysis) is available for isolated aniridia and the Gillespie syndrome. For the WAGR syndrome, high-resolution cytogenetic analysis and fluorescence in situ hybridization (FISH) can be utilized to identify deletions within chromosome band 11p13, where both the PAX6 and WT1 genes are located.

Visual fields associated with chiasmal syndrome usually leads to an MRI. Contrast can delineate arterial aneurysms and will enhance most intrinsic chiasmal lesions. If a mass is confirmed on MRI, an endocrine panel can help determine if a pituitary adenoma is involved.

In patients with functional adenomas diagnosed by other means, visual field tests are a good screen to test for chiasmal involvement. Visual fields tests will delinate chiasmal syndromes because the missing fields will not cross the midline. Junctional scotomas classically show ipsilateral optic disc neuropathy with contralateral superotemporal defects. Bitemporal hemianopia with or without central scotoma is present if the lesions have affected the body of the chiasm. A posterior chiasm lesion should only produce defects on the temporal sides of the central visual field.

The development of accurate and reliable non-invasive ICP measurement methods for VIIP has the potential to benefit many patients on earth who need screening and/or diagnostic ICP measurements, including those with hydrocephalus, intracranial hypertension, intracranial hypotension, and patients with cerebrospinal fluid shunts. Current ICP measurement techniques are invasive and require either a lumbar puncture, insertion of a temporary spinal catheter, insertion of a cranial ICP monitor, or insertion of a needle into a shunt reservoir.

ONH is diagnosed by ophthalmoscopic examination. Patients with ONH exhibit an optic nerve that appears smaller than normal and different in appearance from small optic nerves caused by other eye conditions such as optic (nerve) atrophy.

DM:DD ratio has proven to be a clinically useful measurement to help diagnose optic nerve hypoplasia. Where "DM" represents the distance from Disk to Macula, and "DD" represents Disc Diameter.

The mean disc diameter (DD) is (Vertical diameter of Disc+Horizontal diameter of Disc)divided by 2. The distance between the center of the disc and the macula is DM.

"Interpretation:" When the ratio of DM to DD is greater than 3, ONH is suspected, and when it is greater than 4, Optic Nerve Hypoplasia is definite.

Children with blue diaper syndrome are put on restricted diets. This is in effort to reduce kidney damage. Restrictions include: calcium, protein, vitamin D, and tryptophan. Calcium is restricted to help prevent kidney damage. Examples of food with high levels of tryptophan include turkey and warm milk.

Antibiotics may be used to control or eliminate particular intestinal bacteria. Nicotinic acid may be used to control intestinal infections.

Genetic counseling can also be beneficial, as well as taking part in clinical trials.

Jalili syndrome is a genetic disorder characterized by the combination of cone-rod dystrophy of the retina and amelogenesis imperfecta. It was characterized in 1988 by Dr. I. K. Jalili and Dr. N. J. D. Smith, following the examination of 29 members of an inbred, Arab family living within the Gaza Strip.

Frank ter Haar-syndrome (FTHS), also known as Ter Haar-syndrome, is a rare disease characterized by abnormalities that affect bone, heart, and eye development. Children born with the disease usually die very young.

A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems (especially the nervous system, muscles, and intestines) in affected infants. The most common subtype is CDG-Ia (also referred to as PMM2-CDG) where the genetic defect leads to the loss of phosphomannomutase 2, the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate.

Acorea, microphthalmia and cataract syndrome is a rare genetically inherited condition.

Clinical examination will show an abnormal optic disc, either swollen or atrophic. Optociliary shunt vessels may be seen; the combination of these with progressive visual loss and optic disc atrophy is known as the Hoyt-Spencer triad. Visual acuity is usually but not always reduced.

When ONSM is suspected, MRI of the brain or orbits should be performed. This will usually show characteristic findings and confirm the diagnosis.

The cause of this condition is not presently known. It appears to be inherited in an autosomal dominant fashion.