Clinical vampirism, more commonly called Renfield's syndrome or Renfield syndrome, is an obsession with drinking blood. The earliest formal presentation of clinical vampirism to appear in the psychiatric literature, with the psychoanalytic interpretation of two cases, was contributed by Richard L. Vanden Bergh and John F. Kelley in 1964. As the authors point out, brief and sporadic reports of blood-drinking behaviors associated with sexual pleasure have appeared in the psychiatric literature at least since 1892 with the work of Austrian forensic psychiatrist Richard von Krafft-Ebing. Many medical publications concerning clinical vampirism can be found in the literature of forensic psychiatry, with the unusual behavior reported as one of many aspects of extraordinary violent crimes. The behavior has never gained official recognition by the psychiatric profession and is not found in any edition of the "International Classification of Diseases" or the "Diagnostic and Statistical Manual of Mental Disorders".

One important factor may be differences or changes in parts of the brain known to be involved in representing body shape (e.g., see proprioception and body image). A neuroimaging study of two people diagnosed with clinical lycanthropy showed that these areas display unusual activation, suggesting that when people report their bodies are changing shape, they may be genuinely perceiving those feelings.

Affected individuals believe that they are in the process of transforming into an animal or have already transformed into an animal. It has been associated with the altered states of mind that accompany psychosis (the that typically involves delusions and hallucinations) with the transformation only seeming to happen in the mind and behavior of the affected person.

A study on lycanthropy from the McLean Hospital reported on a series of cases and proposed some diagnostic criteria by which lycanthropy could be recognised:

- A patient reports in a moment of lucidity or reminiscence that they sometimes feel as an animal or have felt like one.

- A patient behaves in a manner that resembles animal behavior, for example howling, growling, or crawling.

According to this criteria, either a delusional belief in current or past transformation or behavior that suggests a person thinks of themselves as transformed is considered evidence of clinical lycanthropy. The authors note that, although the condition seems to be an expression of psychosis, there is no specific diagnosis of mental or neurological illness associated with its behavioral consequences.

DSM-IV Criteria

Clinical Lycanthropy is thought to be a cultural manifestation of schizophrenia due to the first 4 symptomatic criteria. The first criteria are delusions, and this fits clinical lycanthropy because a person believing that he or she turns into an animal is a delusion. The second symptom is hallucination, and people with clinical lycanthropy have vivid hallucinations of being an animal, and having traits that animal has, whether it be claws, fur, fangs, or whatever that particular animal has. The next symptom is disorganized speech, from a certain human, cultural perspective. The people who have the diagnosis of clinical lycanthropy often emit the sounds of the animal which they believe they become. So, if a person believes that he or she is a werewolf, they may begin to howl under the moon or sometimes even in the daylight. The last symptom that matches schizophrenia is grossly disorganized behavior. This is appropriate because individuals with clinical lycanthropy often act like the animal they believe they have become, including living outside and changing their diet.

It also seems that lycanthropy is not specific to an experience of human-to-wolf transformation; a wide variety of creatures have been reported as part of the shape-shifting experience. A review of the medical literature from early 2004 lists over thirty published cases of lycanthropy, only the minority of which have wolf or dog themes. Canines are certainly not uncommon, although the experience of being transformed into a hyena, cat, horse, bird or tiger has been reported on more than one occasion. Transformation into frogs, and even bees, has been reported in some instances. In Japan, transformation into foxes and dogs was usual (, ). A 1989 case study described how one individual reported a serial transformation, experiencing a change from human to dog, to horse, and then finally cat, before returning to the reality of human existence after treatment. There are also reports of people who experienced transformation into an animal only listed as "unspecified".

There is a case study of a psychiatric patient who had both clinical lycanthropy and Cotard delusion. The term "ophidianthropy" refers to the delusion that one has been transformed into a snake. Two case studies have been reported.

Species dysphoria is the experience of dysphoria, sometimes including clinical lycanthropy (delusion or hallucination of one's self as an animal) and dysmorphia (excessive concern over one's body image), associated with the feeling that one's body is of the wrong species. Earls and Lalumière (2009) describe it as "the sense of being in the wrong (species) body... a desire to be an animal". Outside of psychological literature, the term is common within the otherkin and therian communities. The phenomenon is sometimes experienced in the context of sexual arousal to the image of one's self as an animal.

Very few cases of the syndrome have been described, and the published reports that do exist describe clinical vampirism as behaviors that are subsumed under more conventional psychiatric diagnostic categories such as schizophrenia or paraphilia. A case of vampirism in Turkey reported in 2012 was discussed as an unusual feature of a patient diagnosed with dissociative identity disorder and post-traumatic stress disorder. While not referencing the literature on Renfield's syndrome, two Irish psychiatrists surveyed the psychiatric literature on vampirism as evidence of a changing discourse in psychiatry from the narrative of case studies to the depersonalized discourse of checklist diagnostic criteria.

A number of murderers have performed seemingly vampiric rituals upon their victims. Serial killers Peter Kürten and Richard Trenton Chase were both called "vampires" in the tabloids after they were discovered drinking the blood of the people they murdered. Similarly, in 1932, an unsolved murder case in Stockholm, Sweden was nicknamed the "Vampire murder", due to the circumstances of the victim's death.Clinical vampirism in the context of criminal acts of violence, as well as "consensual" vampirism as a social ritual, have been extensively documented in the many works of Katharine Ramsland. Others have commented upon the psychiatric implications of "vampire cults" among adolescents.

"Species dysphoria" is informally used mainly in psychological literature to compare the experiences of some individuals to those in the transgender community. Otherkin and therian communities have also used it to describe their experiences.

In a 2008 study by Gerbasi "et al.", 46% of people surveyed who identified as being in the furry fandom, (usually defined as a person who enjoys anthropomorphic animals, occasionally to an almost obsessive degree), answered "yes" to the question "Do you consider yourself to be less than 100% human?" and 41% answered "yes" to the question "If you could become 0% human, would you?" Questions that Gerbasi states as being deliberately designed to draw parallels with gender dysphoria, specifying "a persistent feeling of discomfort" about the human body and the feeling that the person was the "non-human species trapped in a human body", were answered "yes" by 24% and 29% of respondents, respectively. Likewise, these studies support the fact that the therianthropic, otherkin and furry communities are very similar in nature and are often interconnected.

As described by those who experience it, species dysphoria may include sensations of supernumerary phantom limbs associated with the species, such as phantom wings or claws. Species dysphoria involves feelings of being an animal or other creatures "trapped in" a human body and so, is considered different from the traditional definition of clinical lycanthropy, in which the patient believes they have actually been transformed into an animal or have the ability to physically shapeshift. However, some cases that have been labeled as "clinical lycanthropy" actually seem to be cases of species dysphoria, involving persons who have no delusion of transformation but instead have feelings of being in some way a non-human animal, while still acknowledging they possess a human form. Keck "et al." propose a redefinition for clinical lycanthropy that covers species dysphoric behaviours observed in several patients, including verbal reports, "during intervals of lucidity or retrospectively, that he or she was a particular animal" and behaving "in the manner of a particular animal, i.e. howling, growling, crawling on all fours". Keck "et al." describe one patient as a depressed individual who "had always suspected he was a cat" and "laments his lack of fur, stripes and a tail". Except for the persistent feeling of being feline, the patient's "thought processes and perception" were "usually logical".

Involutional melancholia is classically treated with antidepressants and mood elevators.

Electroconvulsive therapy may also be used. Mid-century, there was a consensus that the technique indeed 'yields the best results in the long-lasting depressions of the change of life, the so-called "involutional melancholias", which before this form of treatment was introduced often required years of hospitalization'. The 21st century also records 'an excellent and rapid clinical response found in melancholia of recent onset...in older rather than younger patients' with ECT

Involutional melancholy's 'course was chronic, with agitation, depersonalization and delusions of bodily change and guilt' featuring strongly, but 'without manic features'. Symptoms of fear are also considered to occur, as well as despondency and hypochondriacal delusions. The late onset of the disorder was matched with a prolonged course with poor prognosis and/or deterioration, in the absence of treatment.

Affective disorders in patients with MD can only be detected by means of a clinician-administered diagnostic interview. Organic exclusion rules and other criteria are used in making the diagnosis of MD.

Somatic manifestations of MD are distinguished by an extreme diversity and include headaches, back pain, abdominal pain etc. Pathological behaviour masking depression may take the form of compulsive gambling, compulsive work, changes in arousal or orgasmic function, decreased libido or, on the contrary, impulsive sexual behaviour, alcoholism, drug addiction and more.

FXTAS can be diagnosed using a combination of molecular, clinical, and radiological findings. In order for individuals to acquire FXTAS, they must first be permutation carriers, having between 55-200 CGG trinucleotide repeat expansion of the FMR1 gene. A definite, probable, or possible diagnosis of FXTAS can be assigned based on a clinician's confidence based on combined clinical or radiological findings in conjunction with the molecular permutation.

Clinical findings are divided into major and minor symptoms. Major symptoms include intention tremor and gait ataxia. Minor symptoms such as parkinsonism, short-term memory deficit, and executive function decline can further contribute to a diagnosis of FXTAS. Radiological findings are similarly divided into major and minor categories. As patients with FXTAS can have distinct brain scans from other movement disorders, a scan showing white matter lesions of the middle cerebellar peduncle is a major finding that can be attributed to FXTAS. Overall or generalized brain tissue atrophy and cerebral white matter lesions can also be minor indicators for a diagnosis.

For a definite diagnosis to be made, a major radiological finding and one major clinical finding must be present. Probable diagnosis can be made off either a major radiological finding and a minor clinical finding or two major clinical findings alone. The possible category for diagnosis can be made with a minor radiological finding and a major clinical finding.

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.

The progression of symptoms varies widely between each case of FXTAS; the onset of symptoms may be gradual, with progression of the disease spanning multiple years or decades. Alternatively, symptoms may progress rapidly.

FXTAS has shown strong age-dependent penetrance, afflicting older permutation carriers with greater prevalence. Male carriers, age 50 and above have a 30% chance of acquiring FXTAS, while male carriers, age 75 and above, have a 75% chance of developing FXTAS. While initially described to affect male carriers, female carriers of the FMR1 gene mutation have also been found to develop FXTAS. However, due to X-inactivation, female carriers are much less likely to develop classic ataxia and tremor signs for FXTAS, instead demonstrating symptoms such as fibromyalgia, thyroid disease, hypertension, and seizures.

Heterogeneous medical condition in medicine are those medical conditions which have several etiologies, like hepatitis or diabetes. Medical conditions are normally defined pathologically (liver inflammation) or clinically (excessive urination) and not etiologically, and therefore it is normal to have more than one cause for them. The word is used as an opposition to homogeneous, meaning that given a group of patients, the disease is the same for all of them.

When a condition is heterogeneous, it is normally divided in endotypes.

The diagnosis of HPS is established by clinical findings of hypopigmentation

of the skin and hair, characteristic eye findings, and demonstration of absent

dense bodies on whole mount electron microscopy of platelets. Molecular

genetic testing of the HPS1 gene is available on a clinical basis for

individuals from northwestern Puerto Rico. Molecular testing of the HPS3 gene

is available on a clinical basis for individuals of central Puerto Rican or

Ashkenazi Jewish heritage. Sequence analysis is available on a clinical basis

for mutations in HPS1 and HPS4. Diagnosis of individuals with other types of

HPS is available on a research basis only.

Because CAPS is extremely rare and has a broad clinical presentation, it is difficult to diagnose, and a significant delay exists between symptom onset and definitive diagnosis. There are currently no clinical or diagnostic criteria for CAPS based solely on clinical presentation. Instead, diagnosis is made by genetic testing for "NLRP3" mutations. Acute phase reactants and white blood cell count are usually persistently elevated, but this is aspecific for CAPS.

Diagnostic techniques for this condition can be done to offer a DDx, via lectin histochemistry to distinguish between α-mannosidosis and beta-mannosidosis.

A diagnosis of beta-mannosidosis is suspected based on the persons clinical presentation. Urine testing to identify abnormal oligosaccharides is a useful screening test, and enzymatic analysis or molecular testing can be used for confirmation.

An endotype is a subtype of a condition, which is defined by a distinct functional or pathobiological mechanism. This is distinct from a phenotype, which is any observable characteristic or trait of a disease, such as morphology, development, biochemical or physiological properties, or behavior, without any implication of a mechanism. It is envisaged that patients with a specific endotype present themselves within phenotypic clusters of diseases.

One example is asthma, which is considered to be a syndrome, consisting of a series of endotypes. This is related to the concept of disease entity

Testicular biopsy would confirm the absence of spermatozoa. Seminal plasma protein TEX101 was proposed for differentiation of Sertoli cell-only syndrome from maturation arrest and hypospermatogenesis. And a clinical trial at Mount Sinai Hospital, Canada started testing this hypothesis in 2016.

Clinical:

Patients often present with a history of fever of unknown origin, muscular weakness, poor development, abnormal dentition, normal serum calcium, phosphorus, and alkaline phosphatase levels. Associated clinical findings also include glaucoma, photosensitivity, heart block, foot deformities, and chronic psoriasiform skin lesions.

Radiological:

Classic radiologic findings were first described by Edward B. Singleton and David Merten in 1973.

Typical radiographic appearances include skeletal demineralization, expanded shafts of the metacarpals and phalanges with widenend medullary cavities, cardiomegaly, and intramural calcification of the proximal aorta with occasional extension into the aortic or mitral valves.

Other commonly seen radiographic findings include shallow acetabular fossa, subluxation of the femoral head, coxa valga, hypoplastic radial epiphysis, soft tissue calcifications between the radius and ulna, constriction of the proximal radial shaft, acro-osteolysis, and equinovarus foot deformities.

The prevalence of MCI varies by age. The prevalence of MCI among different age groups is as follows: 6.7% for ages 60–64; 8.4% for ages 65–69, 10.1% for ages 70–74, 14.8% for ages 75–79, and 25.2% for ages 80–84. After a two-year follow-up, the cumulative incidence of dementia among individuals who are over 65 years old and were diagnosed with MCI was found to be 14.9%.

Globally, approximately 16% of the population over the age of 70 experiences some type of mild cognitive impairment.

There is evidence suggesting that although amnestic MCI patients may not meet neuropathologic criteria for Alzheimer's disease, patients may be in a transitional stage of evolving Alzheimer's disease; patients in this hypothesized transitional stage demonstrated diffuse amyloid in the neocortex and frequent neurofibrillary tangles in the medial temporal lobe. Alternatively, many individuals develop neurofibrillary tangles without amyloid, a pattern termed primary age-related tauopathy.

There is emerging evidence that magnetic resonance imaging can observe deterioration, including progressive loss of gray matter in the brain, from mild cognitive impairment to full-blown Alzheimer disease. A technique known as PiB PET imaging is used to clearly show the sites and shapes of beta amyloid deposits in living subjects using a tracer that binds selectively to such deposits. Such tools may help greatly in assisting clinical research for therapies.

Norrie disease and other NDP related diseases are diagnosed with the combination of clinical findings and molecular genetic testing. Molecular genetic testing identifies the mutations that cause the disease in about 85% of affected males. Clinical diagnoses rely on ocular findings. Norrie disease is diagnosed when grayish-yellow fibrovascular masses are found behind the eye from birth through three months. Doctors also look for progression of the disease from three months through 8–10 years of age. Some of these progressions include cataracts, iris atrophy, shallowing of anterior chamber, and shrinking of the globe. By this point, people with the condition either have only light perception or no vision at all.

Molecular genetic testing is used for more than an initial diagnosis. It is used to confirm diagnostic testing, for carrier testing females, prenatal diagnosis, and preimplantation genetic diagnosis. There are three types of clinical molecular genetic testing. In approximately 85% of males, mis-sense and splice mutations of the NDP gene and partial or whole gene deletions are detected using sequence analysis. Deletion/duplication analysis can be used to detect the 15% of mutations that are submicroscopic deletions. This is also used when testing for carrier females. The last testing used is linkage analysis, which is used when the first two are unavailable. Linkage analysis is also recommended for those families who have more than one member affected by the disease.

On MRI the retinal dysplasia that occurs with the syndrome can be indistinguishable from persistent hyperplastic primary vitreous, or the dysplasia of trisomy 13 and Walker–Warburg syndrome.

HPS is one of the rare lung diseases currently being studied by The Rare Lung Diseases Consortium (RLDC). The RLDC is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), of the National Center for Advancing Translational Sciences (NCATS). The RLDC is dedicated to developing new diagnostics and therapeutics for patients with rare lung diseases, through collaboration between the NIH, patient organizations and clinical investigators.