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.

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

The syndromes within CAPS overlap clinically, and patients may have features of more than one disorder. In a retrospective cohort of 136 CAPS patients from 16 countries, the most prevalent clinical features were fever (84% of cases, often with concurrent constitutional symptoms such as fatigue, malaise, mood disorders or failure to thrive), skin rash (either urticarial or maculopapular rash; 97% of cases) especially after cold exposure, and musculoskeletal involvement (myalgia, arthralgia, and/or arthritis, or less commonly joint contracture, patellar overgrowth, bone deformity, bone erosion and/or osteolytic lesion; 86% of cases). Less common features included ophthalmological involvement (conjunctivitis and/or uveitis, or less commonly optic nerve atrophy, cataract, glaucoma or impaired vision; 71% of cases), neurosensory hearing loss (42% of cases), neurological involvement (morning headache, papilloedema, and/or meningitis, or less commonly seizure, hydrocephalus or mental retardation; 40% of cases), and AA amyloidosis (4% of cases). Age of onset is typically in infancy or early childhood. In 57% of cases, CAPS had a chronic phenotype with symptoms present almost daily, whereas the remaining 43% of patients experienced only acute episodes. Up to 56% of patients reported a family history of CAPS. Previous studies confirm these symptoms, although the exact reported rates vary.

Symptoms(and signs) that are consistent with this disorder are the following:

Autoimmune polyendocrine syndrome type 2, a form of autoimmune polyendocrine syndrome also known as Schmidt's syndrome, or APS-II, is the most common form of the polyglandular failure syndromes. It is heterogeneous and has not been linked to one gene. Rather, individuals are at a higher risk when they carry a particular human leukocyte antigen (HLA-DQ2, HLA-DQ8 and HLA-DR4). APS-II affects women to a greater degree than men.

Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin 1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome (FCAS, formerly termed familial cold-induced urticaria), the Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID, also called chronic infantile neurologic cutaneous and articular syndrome or CINCA) that were originally thought to be distinct entities, but in fact share a single genetic mutation and pathogenic pathway.

The variable presentation of ROHHAD includes the following main symptoms:

- Hyperphagia and obesity by age of 10 years - (median age 3 years);

- Respiratory Manifestations:

- Alveolar Hypoventilation (median onset age 6.2 years);

- Cardiorespiratory arrest;

- Reduced Carbon Dioxide Ventilatory Response;

- Obstructive sleep apnea.

- Thermal or other hypothalamic dysregulations, with autonomic dysregulation by median age 3.6 years:

- Failed Growth Hormone Stimulation;

- Adipsic hypernatremia (inability to feel thirst to keep normal hydration);

- Hypernatremia;

- Hyperprolactinemia;

- Hyperphagia;

- Diabetes insipidus;

- Ophthalmologic Manifestations;

- Thermal Dysregulation;

- Gastrointestinal dysmotility;

- Altered Perception of Pain;

- Altered Sweating;

- Cold Hands and Feet.

- Neurobehavioral disorders;

- Tumors of neural crest origin.

Clinically overlapping cases exist because CCHS phenotype can also include autonomic nervous system dysregulation, or tumors of neural crest origin.

The natural history of MWS is not well known: many patients died in infancy and clinical follow-up has been reported in few surviving adults. However, diagnosis may be more difficult to establish in adults patients, such as: blepharophimosis, contractures, growth retardation, and developmental delay, whereas minor face anomalies are less noticeable as the patient grows older. Throughout the development of the patient from young child to older adult changes the behavior drastically, from kindness to restless and hyperactive to aggressive.

Autoimmune polyendocrine syndromes (APSs), also called autoimmune polyglandular syndromes (APSs), polyglandular autoimmune syndromes (PGASs), or polyendocrine autoimmune syndromes, are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected.There are three types of APS or (in terms that mean the same thing) three APSs, and there are a number of other diseases which have endocrine autoimmunity.

Most of the signs of MWS are present during the neonatal period. The most common signs at this state are multiple congenital joint contractures, dysmorphic features with mask-like face, blepharophimosis, ptosis, micrognathia, cleft or high arched palate, low-set ears, arachnodactyly, chest deformation as pectus, kyphoscoliosis and absent deep tendon reflexes are frequent minor malformations have also been described and consist of renal anomalies, cardiovascular abnormalities, hypospadias, omphalomesenteric duct, hypertriphic pyloric stenosis, duodenal bands, hyoplastic right lower lobe of the lung, displacement of the larynx to the right and vertebral abnormalities, cerebral malformations.

- 75% of children with MWS have blepharophimosis, small mouth, micrognathia, kyphosis/scoliosis, radio ulnar synostose and multiple contractures.

- They have severe developmental delay; congenital joint contractures and blepharophimosis should be present in every patient

- 2 out of 3 of the following signs should be manifested: post natal growth, mask-like faces, retardation, and decreased muscular mass.

- Some may require additional signs such as; micrognathia, high arched or cleft palate, low set ears, kyphoscoliosis.

- The symptoms of MWS are normally diagnosed during the newborn period

Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD syndrome) is a very rare disease affecting approximately 75 people worldwide. Patients with ROHHAD, as well as patients with congenital central hypoventilation syndrome (CCHS) have damage to the mechanism governing proper breathing. ROHHAD syndrome is a disease that is potentially lethal and incurable. Fifteen patients with ROHHAD were evaluated by Diego Ize-Ludlow et al. work published in 2007.

This condition is characterised by symmetrical lesions on the temples resembling forceps marks. It is characterized a puckered skin due to a virtual absence of subcutaneous fat. It is apparent at birth. Other lesions that may be present include puffy, wrinkled skin around the eyes and/or abnormalities of the eyelashes, eyebrows, and eyelids. The eyebrows may be up slanting or outward slanting. Occasionally the bridge of the nose may appear flat, while the tip may appear unusually rounded. The chin may be furrowed. The upper lip may be prominent with a down turned mouth. Other features that have been reported include dysplastic and low set ears, linear radiatory impressions on the forehead and congenital horizontal nystagmus.

Those with the Setleis syndrome may be missing eyelashes on both the upper and lower lids or may have multiple rows of lashes on the upper lids but none on the lower lids.A possible association with intra abdominal cancer has been reported but to date this has not been confirmed in other studies.

Each "type" of this condition has a different cause, in terms of IPEX syndrome is inherited in males by an x-linked recessive process. FOXP3 gene, whose cytogenetic location is Xp11.23, is involved in the mechanism of the IPEX condition.

PEHO syndrome is a progressive encephalopathy with edema, hypsarrhythmia and optic atrophy. It is a very rare disease, one of the Finnish heritage diseases, although approximately half of the cases reported so far are not-Finnish and have been described worldwide .

It has been suggested that it may also be present in Australian and American populations.

Focal facial dermal dysplasia (FFDD) is a rare genetically heterogeneous group of disorders that are characterized by congenital bilateral scar like facial lesions, with or without associated facial anomalies. It is characterized by hairless lesions with fingerprint like puckering of the skin, especially at the temples, due to alternating bands of dermal and epidermal atrophy.

This condition is also known as Brauer syndrome (hereditary symmetrical aplastic nevi of temples, bitemporal aplasia cutis congenita, bitemporal aplasia cutis congenita: OMIM ) and Setleis syndrome (facial ectodermal dysplasia: OMIM ).

The severity of different forms of PCH varies, but many children inheriting the mutated gene responsible do not survive infancy or childhood; nevertheless, some individuals born with PCH have reached adulthood.

Clinically, three distinct patterns of palmoplantar keratoderma may be identified: diffuse, focal, and punctate.

Pontocerebellar hypoplasia is classified as follows:

Pontine and cerebellar hypoplasia is also observed in certain phenotypes of X-linked mental retardation – so called MICPCH.

The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome. Early onset partial aniridia, cerebellar ataxia, and mental retardation are hallmark of syndrome. The iris abnormality is specific and seems pathognomonic of Gillespie syndrome. The aniridia consisting of a superior coloboma and inferior iris hypoplasia, foveomacular dysplasia.

Atypical Gillespie syndrome associated with bilateral ptosis, exotropia, correctopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation.

Neurological signs ar nystagmus, mild craniofacial asymmetry, axial hypotonia, developmental delay, and mild mental retardation. Mariën P did not support the prevailing view of a global mental retardation as a cardinal feature of Gillespie syndrome but primarily reflect cerebellar induced neurobehavioral dysfunctions following disruption of the cerebrocerebellar anatomical circuitry that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS).

Congenital pulmonary stenosis and helix dysplasia can be associated.

Distal hereditary motor neuronopathies (distal HMN, dHMN), sometimes also called distal hereditary motor neuropathies, are a genetically and clinically heterogeneous group of motor neuron diseases that result from genetic mutations in various genes and are characterized by degeneration and loss of motor neuron cells in the anterior horn of the spinal cord and subsequent muscle atrophy.

Although they can hardly be distinguished from hereditary motor and sensory neuropathies on the clinical level, dHMNs are considered a separate class of disorders.

Diffuse palmoplantar keratoderma is a type of palmoplantar keratoderma that is characterized by an even, thick, symmetric hyperkeratosis over the whole of the palm and sole, usually evident at birth or in the first few months of life. Restated, diffuse palmoplantar keratoderma is an autosomal dominant disorder in which hyperkeratosis is confined to the palms and soles. The two major types can have a similar clinical appearance:

- "Diffuse epidermolytic palmoplantar keratoderma" (also known as "Palmoplantar keratoderma cum degeneratione granulosa Vörner," "Vörner's epidermolytic palmoplantar keratoderma", and "Vörner keratoderma") is one of the most common patterns of palmoplantar keratoderma, an autosomal dominant condition that presents within the first few months of life, characterized by a well-demarcated, symmetric thickening of palms and soles, often with a "dirty" snakeskin appearance due to underlying epidermolysis.

- "Diffuse nonepidermolytic palmoplantar keratoderma" (also known as "Diffuse orthohyperkeratotic keratoderma," "Hereditary palmoplantar keratoderma," "Keratosis extremitatum progrediens," "Keratosis palmoplantaris diffusa circumscripta," "Tylosis," "Unna–Thost disease", and "Unna–Thost keratoderma") is inherited as an autosomal dominant condition and is present from infancy, characterized by a well-demarcated, symmetric, often "waxy" keratoderma involving the whole of the palms and soles.

In 1993, A. E. Hardnig proposed to classify hereditary motor neuropathies into seven groups based on age at onset, mode of inheritance, and presence of additional features. This initial classification has since been widely adopted and expanded and currently looks as follows:

Note: Acronym "HMN" is also used interchangeably with "DHMN".

While inclusion criteria for Rud syndrome have varied considerably, the major manifestations includes congenital ichthyosis, hypogonadism, small stature, mental retardation, and epilepsy. Ocular findings were inconsistently reported and included strabismus, blepharoptosis, blepharospasm, glaucoma, cataract, nystagmus, and retinitis pigmentosa. Other systemic includes metabolic, bony, neurologic, and muscular abnormalities.

Marburg acute multiple sclerosis, also known as Marburg multiple sclerosis or acute fulminant multiple sclerosis, is considered one of the multiple sclerosis borderline diseases, which is a collection of diseases classified by some as MS variants and by others as different diseases. Other diseases in this group are neuromyelitis optica (NMO), Balo concentric sclerosis, and Schilder's disease. The graver course is one form of malignant multiple sclerosis, with patients reaching a significant level of disability in less than five years from their first symptoms, often in a matter of months.

Sometimes Marburg MS is considered a synonym for tumefactive MS, but not for all authors.

Rud syndrome is a poorly characterized disorder, probably of X-linked recessive inheritance, named after Einar Rud who described 2 patients with the case in 1927 and 1929. It was argued that all reported cases of Rud syndrome are genetically heterogeneous and significantly differ from the original case reports of Rud and that the designation Rud syndrome should be eliminated and that the patients with such diagnosis should be reassigned to other syndromes, such as Refsum disease and Sjögren-Larsson syndrome.Some consider Rud syndrome and Sjögren-Larsson syndrome the same entity and that Rud syndrome doesn't exist.