Aicardi–Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi syndrome, is a rare, usually early onset childhood, inflammatory disorder most typically affecting the brain and the skin (neurodevelopmental disorder). The majority of affected individuals experience significant intellectual and physical problems, although this is not always the case. The clinical features of AGS can mimic those of "in utero" acquired infection, and some characteristics of the condition also overlap with the autoimmune disease systemic lupus erythematosus (SLE). Following an original description of eight cases in 1984, the condition was first referred to as 'Aicardi–Goutières syndrome' (AGS) in 1992, and the first international meeting on AGS was held in Pavia, Italy, in 2001.

AGS can occur due to mutations in any one of a number of different genes, of which seven have been identified to date, namely: TREX1, RNASEH2A, RNASEH2B, RNASEH2C (which together encode the Ribonuclease H2 enzyme complex), SAMHD1, ADAR1, and IFIH1 (coding for MDA5). This neurological disease occurs in all populations worldwide, although it is almost certainly under-diagnosed. To date (2014) at least 400 cases of AGS are known.

Griscelli syndrome is a rare autosomal recessive disorder characterized by albinism (hypopigmentation) with immunodeficiency, that usually causes death by early childhood.

Treatment of glaucoma in iridogoniodysgenesis is primarily surgical.

It is listed as a "rare disease" by the Office of Rare Diseases (ORD). This means that Iridogoniodysgenesis, dominant type, or a subtype of Iridogoniodysgenesis, dominant type, affects less than 200,000 people in the US population.

Griscelli syndrome is defined by the characteristic hypopigmentation, with frequent pyogenic infection, enlargement of the liver and spleen, a low blood neutrophil level, low blood platelet level, and immunodeficiency. Very often there is also impaired natural killer cell activity, absent delayed-type hypersensitivity and a poor cell proliferation response to antigenic challenge. This may be caused by the loss of three different genes, each of which has different additional effects, resulting in three types of syndrome. Its inheritance is autosomal recessive.

Examination of the hair in this syndrome may be useful. Under light microscopy, these hairs exhibit bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, the hairs appear monotonously white.

Laboratory: normal metabolic and infective screening. An increase in the number of white cells (particularly lymphocytes) in the CSF, and high levels of interferon-alpha activity and neopterin in the CSF are important clues - however, these features are not always present. More recently, a persistent elevation of mRNA levels of interferon-stimulated gene transcripts have been recorded in the peripheral blood of almost all cases of AGS with mutations in "TREX1", "RNASEH2A", "RNASEH2C", "SAMHD1", "ADAR1" and "IFIH1", and in 75% of patients with mutations in "RNASEH2B". These results are irrespective of age. Thus, this interferon signature appears to be a very good marker of disease.

Genetics: pathogenic mutations in any of the seven genes known to be involved in AGS.

A triplex tetra-primer ARMS-PCR method was developed for the simultaneous detection of C677T and A1298C polymorphisms with the A66G MTRR polymorphism in a single PCR reaction.

Methylene tetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the "MTHFR" gene. Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Natural variation in this gene is common in healthy people. Although some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer's disease and other forms of dementia, colon cancer, and acute leukemia, findings from small early studies have not been reproduced. Some mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.

Weissenbacher-Zweymüller syndrome affects males and females in the same numbers. About 30 cases have been reported in medical literature. This disorder can be underdiagnosed causing no true frequency in the population. Only 30 cases have been reported in medical literature.

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.

Microlissencephaly is listed in Orphanet database as a rare disease. There is no much information available about the epidemiology of microlissencepahly in literature. A PhD thesis has estimated the prevalence of microlissencepahly in South–Eastern Hungary between July 1992 and June 2006 to be a case every 91,000 live births (0.11:10,000).

Modeling EEC syndrome in vitro has been achieved by reprogramming EEC fibroblasts carrying mutations R304W and R204W into induced pluripotent stem cell (iPSC) lines. EEC-iPSC recapitulated defective epidermal and corneal fates. This model further identified PRIMA-1MET, a small compound that was identified as a compound targeting and reactivating p53 mutants based on a cell-based screening for rescuing the apoptotic activity of p53, as efficient to rescue R304W mutation defect. Of interest, similar effect had been observed on keratinocytes derived from the same patients. PRIMA-1MET could become an effective therapeutic tool for EEC patients.

Further genetic research is necessary to identify and rule out other possible loci contributing to EEC syndrome, though it seems certain that disruption of the p63 gene is involved to some extent. In addition, genetic research with an emphasis on genetic syndrome differentiation should prove to be very useful in distinguishing between syndromes that present with very similar clinical findings. There is much debate in current literature regarding clinical markers for syndromic diagnoses. Genetic findings could have great implications in clinical diagnosis and treatment of not only EEC, but also many other related syndromes.

One 10-year-old girl with Crigler–Najjar syndrome type I was successfully treated by liver cell transplantation.

The homozygous Gunn rat, which lacks the enzyme uridine diphosphate glucuronyltransferase (UDPGT), is an animal model for the study of Crigler–Najjar syndrome. Since only one enzyme is working improperly, gene therapy for Crigler-Najjar is a theoretical option which is being investigated.

Iridogoniodysgenesis, dominant type (type 1, IRID1) refers to a spectrum of diseases characterized by malformations of the irido-corneal angle of the anterior chamber of the eye. Iridogoniodysgenesis is the result of abnormal migration or terminal induction of neural crest cells. These cells lead to formation of most of the anterior segment structures of the eye (corneal stroma & endothelium, iris stroma, trabeculum).

There is no cure as of now. Treatment is directed towards the specific symptoms that are present in each individual. Individuals with hearing loss are able to get treated with hearing aids.

Pelizaeus–Merzbacher disease (PMD) is a rare central nervous system disorder in which coordination, motor abilities, and intellectual function are delayed to variable extents.

Ectrodactyly–ectodermal dysplasia–cleft syndrome, or EEC, and also referred to as EEC syndrome (also known as "Split hand–split foot–ectodermal dysplasia–cleft syndrome") is a rare form of ectodermal dysplasia, an autosomal dominant disorder inherited as an genetic trait. EEC is characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts. Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections, obstruction of the nasolacrimal duct, decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.

This is an autosomal dominant hereditary condition, which tends to produce high rates of inheritance and long chains of generational transmission. All who inherit the gene have at some time in life evidence of piebald hypopigmentation of the hair or skin, most likely both. Historically, persons with extensive piebaldism have experienced abuse of the sort still suffered in the present by albinos, especially in Africa. This has ranged from display of unclothed African piebalds in "freak" shows and post cards of the early twentieth century to the forcing of piebalds (as in the case of albinos) to work long hours exposed to the sun (producing high rates of lethal skin cancers), to the use of piebald humans, including children, in risky medical experiments. The National Organization of Albinism and Hypopigmentation, as well as organizations such as Under the Same Sun, work to promote awareness of all forms of cutaneous variation and their medical implications, and to highlight human rights issues, especially the plight of albinos subject to extreme persecution in parts of Africa.

Piebaldism may be associated with the genes "KIT" or "SNAI2".

In general, gray matter heterotopia is fixed in both its occurrence and symptoms; that is, once symptoms occur, it does not tend to progress. Varying results from surgical resection of the affected area have been reported. Although such surgery cannot reverse developmental disabilities, it may provide full or partial relief from seizures.

Heterotopia are most commonly isolated anomalies, but may be part of a number of syndromes, including chromosomal abnormalities and fetal exposure to toxins (including alcohol).

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.

Central hypoventilation syndrome is a heterogeneous group of seemingly overlapping diseases. Paired-like homeobox 2B (PHOX2B) was confirmed in 2009 as the disease-causing gene in patients with congenital central hypoventilation syndrome (CCHS), a condition present in newborns. This genetic mutation is not present though in those with late-onset central hypoventilation syndrome and hypothalamic dysfunction.

There is no cure for PMD, nor is there a standard course of treatment. Treatment, which is symptomatic and supportive, may include medication for seizures and spasticity. Regular evaluations by physical medicine and rehabilitation, orthopedic, developmental and neurologic specialists should be made to ensure optimal therapy and educational resources. The prognosis for those with Pelizaeus–Merzbacher disease is highly variable, with children with the most severe form (so-called connatal) usually not surviving to adolescence, but survival into the sixth or even seventh decades is possible, especially with attentive care. Genetic counseling should be provided to the family of a child with PMD.

In December 2008, StemCells Inc., a biotech company in Palo Alto, received clearance from the U.S. Food and Drug Administration (FDA) to conduct Phase I clinical trials in PMD to assess the safety of transplanting human neural stem cells as a potential treatment for PMD. The trial was initiated in November 2009 at the University of California, San Francisco (UCSF) Children's Hospital.

Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly (small head) with lissencephaly (smooth brain surface due to absent sulci and gyri). Microlissencephaly is a heterogeneous disorder i.e. it has many different causes and a variable clinical course. Microlissencephaly is a malformation of cortical development (MCD) that occurs due to failure of neuronal migration between the third and fifth month of gestation as well as stem cell population abnormalities. Numerous genes have been found to be associated with microlissencephaly, however, the pathophysiology is still not completely understood.

The combination of lissencephaly with severe congenital microcephaly is designated as microlissencephaly only when the cortex is abnormally thick. If such combination exists with a normal cortical thickness (2.5 to 3 mm), it is known as "microcephaly with simplified gyral pattern" (MSGP). Both MLIS and MSGP have a much more severe clinical course than microcephaly alone. They are inherited in autosomal recessive manner. Prior to 2000, the term “microlissencephaly” was used to designate both MLIS and MSGP.

The majority of patients with neurocutaneous melanosis are asymptomatic and therefore have a good prognosis with few complications. Most are not diagnosed, so definitive data in not available. For symptomatic patients, the prognosis is far worse. In patients without the presence of melanoma, more than 50% die within 3 years of displaying symptoms. While those with malignancy have a mortality rate of 77% with most patients displaying symptoms before the age of 2.

The presence of a Dandy-Walker malformation along with neurocutaneous melanosis, as occurs in 10% of symptomatic patients, further deteriorates prognosis. The median survival time for these patients is 6.5 months after becoming symptomatic.

The incidence in the general population is roughly 0.5%, and clinical symptoms typically appear between 20 to 30 years of age. Once thought to be strictly congenital, these vascular lesions have been found to occur "de novo". It may appear either sporadically or exhibit autosomal dominant inheritance.

Piebaldism is a rare autosomal dominant disorder of melanocyte development. Common characteristics include a congenital white forelock, scattered normal pigmented and hypopigmented macules and a triangular shaped depigmented patch on the forehead. There is nevertheless great variation in the degree and pattern of presentation, even within affected families. In some cases, piebaldism occurs together with severe developmental problems, as in Waardenburg syndrome and Hirschsprung's disease. It has been documented to occur in all races; early photographers captured many images of African piebalds used as a form of amusement, and George Catlin is believed to have painted several portraits of Native Americans of the Mandan tribe who were affected by piebaldism. Piebaldism is found in nearly every species of mammal. It is very common in mice, rabbits, dogs, sheep, deer, cattle and horses—where selective breeding has increased the incidence of the mutation-, but occurs among chimpanzees and other primates only as rarely as among humans. Piebaldism is completely unrelated to acquired or infectious conditions such as vitiligo or poliosis.

"Pie" is a word for multi-colored and "bald" is related to a root word for "skin." Although piebaldism may visually appear to be partial albinism, it is a fundamentally different condition. The vision problems associated with albinism are not usually present as eye pigmentation is normal. Piebaldism differs from albinism in that the affected cells maintain the ability to produce pigment but have that specific function turned off. In albinism the cells lack the ability to produce pigment altogether. Human piebaldism has been observed to be associated with a very wide range and varying degrees of endocrine disorders, and is occasionally found together with heterochromia of the irises, congenital deafness, or incomplete gastrointestinal tract development, possibly all with the common cause of premature cutting off of human fetal growth hormone during gestation. Piebaldism is a kind of neurocristopathy, involving defects of various neural crest cell lineages that include melanocytes, but also involving many other tissues derived from the neural crest. Oncogenic factors, including mistranscription, are hypothesized to be related to the degree of phenotypic variation among affected individuals.