Allen Avinoam Kowarski et al. described the first two cases of the Kowarski syndrome in 1978. The group speculated that their patients' growth impairment was caused by a mutation in the growth hormone gene, which altered the structure of their secreted growth hormone, reducing its biological activity while retaining its ability to bind the antibodies used in the RIA-GH. Their RIA-GH measured growth hormone of reduced bioactivity. The children retained the ability to respond to treatment with active growth hormone.

The speculation of Kowarski et al. was confirmed by Valenta et al in 1985, Takahshi et al in 1996 and 1997 and Besson et al in 2005. Valenta et al studied a case of Kowarski syndrome where they confirmed a structural abnormality of the growth hormone molecule. 60 to 90% of circulating growth hormone of the patient was in the form of tetramers and dimers (normal, 14% to 39% in plasma) and the patients' growth hormone polymers were abnormally resistant to conversion into monomers by urea.

Takahashi et al. reported a case of a boy with short stature who was heterozygous for a mutation in the GH1 gene. In this child, growth hormone not only could not activate the GH receptor (GHR) but also inhibited the action of wild type GH because of its greater affinity for GHR and GH-binding protein (GHBP) that is derived from the extracellular domain of the GHR. Thus, a dominant-negative effect was observed.

Takahashi et al. demonstrated in a girl with short stature, a biologically inactive growth hormone resulting from a heterozygous mutation in the GH1 gene. At age 3 years, the girl's height was 3.6 standard deviations below the mean for age and sex. Bone age was delayed by 1.5 years. She had a prominent forehead and a hypoplastic nasal bridge with normal body proportions. She showed lack of growth hormone action despite high immunoassayable GH levels in serum and marked catch-up growth to exogenous GH administration. Results of other studies were compatible with the production of a bioinactive GH, which prevented dimerization of the growth hormone receptor, a crucial step in GH signal transduction.

Besson et al described in 1955 a Serbian patient with Kowarski syndrome who was homozygous for a mutation in the GH1 gene that disrupted the first disulfide bridge in growth hormone. The parents were each heterozygous for the mutation and were of normal stature.

Kowarski syndrome describes cases of growth failure (height and bone age two standard deviations below the mean for age), despite the presence of normal or slightly high blood growth hormone by radioimmunoassay (RIA-GH) and low serum IGF1 (formerly called somatomedin), and who exhibit a significant increase in growth rate following recombinant GH therapy.

The disorder is thought to be related to mutations in the PDE3A gene.

Triple X syndrome occurs in around 1 in 1,000 girls. On average, five to ten girls with triple X syndrome are born in the United States each day.

By 1990, 65 patients had been reported in the literature, with no sex or ethnic preference notable. Some individuals present with minimal malformation; rarely patients have died during infancy as a result of severe central nervous system involvement or respiratory complications. Several syndromes are related to the Freeman–Sheldon syndrome spectrum, but more information is required before undertaking such nosological delineation.

The cause of Primrose syndrome is currently unknown. This condition is extremely rare and seems to spontaneously occur, regardless of family history.

In the case studied by Dalai et al. in 2010, it was found that an abnormally high amount of calcitonin, a hormone secreted by the thyroid gland to stabilize blood calcium levels, was present in the blood serum. This suggests that the thyroid gland is releasing an abnormal amount of calcitonin, resulting in the disruption of calcium level homeostasis. No molecular cause was found, but an expanded microarray analysis of the patient found a 225.5 kb deletion on chromosome 11p between rs12275693 and rs1442927. Whether or not this deletion is related to the syndrome or is a harmless mutation is unknown. The deletion was not present in the patient's mother's DNA sample, but the father's DNA was unavailable.

Urban–Rogers–Meyer syndrome, also known as Prader–Willi habitus, osteopenia, and camptodactyly or Urban syndrome, is an extremely rare inherited congenital disorder first described by Urban et al. (1979). It is characterized by genital anomalies, mental retardation, obesity, contractures of fingers, and osteoporosis, though further complications are known.

Trichorrhexis invaginata (also known as "Bamboo hair" ) is a distinctive hair shaft abnormality that may occur sporadically, either in normal hair or with other hair shaft abnormalities, or regularly as a marker for Netherton's syndrome. The primary defect appears to be abnormal keratinization of the hair shaft in the keratogenous zone, allowing for intussusception of the fully keratinized and hard distal shaft into the incompletely keratinized and soft proximal portion of the shaft.

There are little data on prognosis. Rarely, some patients have died in infancy from respiratory failure; otherwise, life expectancy is considered to be normal.

Most patients with hyper IgE syndrome are treated with long-term antibiotic therapy to prevent staphylococcal infections. Good skin care is also important in patients with hyper IgE syndrome. High-dose intravenous gamma-globulin has also been suggested for the treatment of severe eczema in patients with HIES and atopic dermatitis.

Genitopatellar Syndrome is an autosomal dominant inheritance where the mutation in the KAT6B causes the syndrome. The KAT6B gene is responsible for making an enzyme called histone acetyltransferase which functions in regulating and making of histone which are proteins that attach to DNA and give the chromosomes their shape. The function of histone acetyltransferase produced from KAT6B is unknown but it is considered as a regulator of early developments. There is little known about how the mutation in the KAT6B causes the syndrome but researchers suspects that the mutations occur near the end of the KAT6B gene and causes it to produce shortened acetyltransferase enzyme. The shortened enzyme alters the regulation of other genes. On the other hand, the mutation of KAT6B leading to the specific features of genitopatellar syndrome is still not surely proven.

Triple X syndrome is not inherited, but usually, occurs as an event during the formation of reproductive cells (ovum and sperm). An error in cell division called nondisjunction can result in reproductive cells with additional chromosomes. For example, an oocyte or sperm cell may gain an extra copy of the X chromosome as a result of the non-disjunction. If one of these cells contributes to the genetic makeup of a child, the child will have an extra X chromosome in each of her cells. In some cases, trisomy X occurs during cell division in early embryonic development.

Some females with triple X syndrome have an extra X chromosome in only some of their cells. These cases are called 46,XX/47,XXX mosaics.

"Bamboo hair" is a rare autosomal recessive genodermatosis characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis with failure to thrive. Chronic skin inflammation results in scaling and exfoliation, predisposing these patients to life-threatening infections, sepsis, and dehydration. The Netherton syndrome Mendelian Inheritance in Man is inherited as an autosomal recessive disorder due to mutations of both copies of the "SPINK5" gene (localized to band 5q31-32), which encodes the serine protease inhibitor LEKTI (lymphoepithelial Kazal-type-related inhibitor). LEKTI is expressed in epithelial and mucosal surfaces and in the thymus. Each "SPINK5" mutation leads to a different length of LEKTI protein, resulting in genotype/phenotype correlations in cutaneous severity, susceptibility to atopic dermatitis, growth retardation, skin infection, increased stratum corneum protease activities, and elevated kallikrein levels in the stratum corneum.

Trichorrhexis invaginata, or bamboo hair, is a hair shaft abnormality that occurs as a result of an intermittent keratinizing defect of the hair cortex. Incomplete conversion of the sulfhydryl –SH group onto S-S disulfide bonds in the protein of the cortical fibers leads to cortical softness and subsequent invagination of the fully keratinized distal hair shaft into the softer, abnormally keratinized proximal hair shaft. Intussusception of the distal hair shaft into the proximal hair shaft results in a distinctive ball-and-socket hair shaft deformity. The affected hairs are brittle and breakage is common, resulting in short hairs.

Migratory lesions of ichthyosis linearis circumflexa may be caused by a dermal influx of inflammatory cells that undergo phagocytosis and digestion by keratinocytes, resulting in disruption of keratinization.

Increased transepidermal water loss resulting from the disturbance of corneocyte barrier function in erythroderma may cause profound metabolic abnormalities and hypernatremia, particularly in neonates.

Approximately 200 cases of trichorrhexis invaginata (bamboo hair) have been reported in the literature, but the true incidence is not known. The incidence of trichorrhexis invaginata (bamboo hair) may be as high as 1 case in 50,000 population.

Girls are affected more often by trichorrhexis invaginata (bamboo hair) than boys, but is present in all races.

Hypertension and brachydactyly syndrome (HTNB) also known as Bilginturan syndrome and brachydactyly type E among others is a very rare genetic disorder.

It was first reported in 1973 by N. Bilginturan et al. The estimated prevalence is less than 1 out of 1,000,000.

Genitopatellar syndrome is a rare disorder with characteristic craniofacial features, congenital flexion contractures of the lower limbs, absent or abnormal patellae, urogenital anomalies, and severe psychomotor retardation.

In 2012, it was shown that mutations in the gene KAT6B cause the syndrome.

The true prevalence of PMS has not been determined. More than 1200 people have been identified worldwide according the Phelan-McDermid Syndrome Foundation. However, it is believed to be underdiagnosed due to inadequate genetic testing and lack of specific clinical features. It is known to occur with equal frequency in males and females. Studies using chromosomal microarray for diagnosis indicate that at least 0.5% of cases of ASD can be explained by mutations or deletions in the "SHANK3" gene. In addition when ASD is associated with ID, "SHANK3" mutations or deletions have been found in up to 2% of individuals.

Vici syndrome, also called immunodeficiency with cleft lip/palate, cataract, hypopigmentation and absent corpus callosum, is a rare autosomal recessive congenital disorder characterized by albinism, agenesis of the corpus callosum, cataracts, cardiomyopathy, severe psychomotor retardation, seizures, immunodeficiency, and recurrent severe infections. To date about 50 cases have been reported.

Unlike other autoinflammatory disorders, patients with CANDLE do not respond to IL-1 inhibition treatment in order to stop the autoinflammatory response altogether. This suggests that the condition also involves IFN dysregulation.

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).

The common symptoms in all reported cases of primrose syndrome include ossified pinnae, learning disabilities or mental retardation, hearing problems, movement disorders (ataxia, paralysis, and parkinsonism among others (likely due, in part, to calcification of the basal ganglia), a torus palatinus (a neoplasm on the mouth's hard palate), muscle atrophy, and distorted facial features. Other symptoms usually occur, different in each case, but it is unknown whether or not these symptoms are caused by the same disease.

Vici syndrome is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

The hypothesis of autosomal recessive inheritance of Vici syndrome was strengthened in 2002 with the clinical description of two new cases, one brother and one sister, by Chiyonobu et al.

Abnormal neutrophil chemotaxis due to decreased production of interferon gamma by T lymphocytes is thought to cause the disease.

Both autosomal dominant and recessive inheritance have been described:

Autosomal dominant:

- "STAT3" may present as HIES with characteristic facial, dental, and skeletal abnormalities that has been called Job's Syndrome. A common mnemonic used to remember the symptoms is FATED: coarse or leonine facies, cold staph abscesses, retained primary teeth, increased IgE, and dermatologic problems [eczema]. The disease was linked to mutations in the "STAT3" gene after cytokine profiles indicated alterations in the STAT3 pathway.

Autosomal recessive:

- "DOCK8 -" DOCK8 Immunodeficiency Syndrome (DIDS) presents primarily with immune effects including HEIS. Eczema is prominent, food and environmental allergies are common, and asthma and anaphylaxis has been variably reported.

- "PGM3", a Congenital Disorder of Glycosylation, may present as HIES with neurocognitive impairment and hypomyelination. See PGM3 deficiency.

- "SPINK5" may present as HIES with skin and hair effects such as trichorrhexis invaginata (bamboo hair). See Netherton Syndrome (NTS).

- "TYK2" may present as HIES, although more often only with immunodeficiency.

Kosaki overgrowth syndrome (KOGS) is a rare (27 cases reported by 2017) syndrome caused by mutations in the PDGFRB gene.

The incidence of Fraser syndrome is 0.043 per 10,000 live born infants and 1.1 in 10,000 stillbirths, making it a rare syndrome.

Stimmler syndrome is an autosomal recessive genetic disorder whose symptoms appear before birth or during infancy. In a study of two sisters born within a year of each other, both with Stimmler syndrome, it was found that high levels of alanine, pyruvate, and lactate were present in both the blood and urine. It was believed that the alanine was derived from the pyruvate.