Children with Pfeiffer syndrome types 2 and 3 "have a higher risk for neurodevelopmental disorders and a reduced life expectancy" than children with Pfeiffer syndrome type 1, but if treated, favorable outcomes are possible. In severe cases, respiratory and neurological complications often lead to early death.

It has several different types:

- type 1 - Apert syndrome

- type 2 - Crouzon syndrome

- type 3 - Saethre-Chotzen syndrome

- type 5 - Pfeiffer syndrome

A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation. It also has multiple types:

- type 1 - Noack syndrome; now classified with Pfeiffer syndrome

- type 2 - Carpenter syndrome

- type 3 - Sakati-Nyhan-Tisdale syndrome

- type 4 - Goodman syndrome; now classified with Carpenter syndrome

- type 5 - Pfeiffer syndrome

It has been suggested that the distinction between "acrocephalosyndactyly" versus "acrocephalopolysyndactyly" should be abandoned.

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genotypical root cause of these widely varying, phenotypically-observed disorders. Orofaciodigital syndrome has been found to be a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney disease and polycystic liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.

Acrocephalosyndactylia (or acrocephalosyndactyly) is the common presentation of craniosynostosis and syndactyly.

Orofaciodigital syndrome 1 (OFD1), also called Papillon-League and Psaume syndrome, is an X-linked congenital disorder characterized by malformations of the face, oral cavity, and digits with polycystic kidney disease and variable involvement of the central nervous system.

The syndromes associated with central polydactyly are:

Bardet–Biedl syndrome,

Meckel syndrome,

Pallister–Hall syndrome,

Legius syndrome,

Holt–Oram syndrome,

Also, central polydactyly can be associated with syndactyly and cleft hand.

Other syndromes including polydactyly include acrocallosal syndrome, basal cell nevus syndrome, Biemond syndrome, ectrodactyly-ectodermal dysplasias-cleft lip/palate syndrome, mirror hand deformity, Mohr syndrome, oral-facial-digital syndrome, Rubinstein-Taybi syndrome, short rib polydactyly, and VATER association.

It can also occur with a triphalangeal thumb.

Type VII of radial polydactyly is associated with several syndromes:

Holt–Oram syndrome, Fanconi anemia (aplastic anemia by the age of 6), Townes–Brocks syndrome, and Greig cephalopolysyndactyly (also known to occur with ulnar polydactyly).

Synpolydactyly is a joint presentation of syndactyly (fusion of digits) and polydactyly (production of supernumerary digits). This is often a result of a mutation in the HOX D13 gene.

Types include:

The key problem is the early fusion of the skull, which can be corrected by a series of surgical procedures, often within the first three months after birth. Later surgeries are necessary to correct respiratory and facial deformities.

The RASopathies are developmental syndromes caused by germline mutations (or in rare cases by somatic mosaicism) in genes that alter the Ras subfamily and mitogen-activated protein kinases that control signal transduction, including:

- Capillary malformation-AV malformation syndrome

- Autoimmune lymphoproliferative syndrome

- Cardiofaciocutaneous syndrome

- Hereditary gingival fibromatosis type 1

- Neurofibromatosis type 1

- Noonan syndrome

- Costello syndrome, Noonan-like

- Legius syndrome, Noonan-like

- Noonan syndrome with multiple lentigines, formerly called LEOPARD syndrome, Noonan-like

Café au lait spots can arise from diverse and unrelated causes:

- Having six or more café au lait spots greater than 5 mm in diameter before puberty, or greater than 15 mm in diameter after puberty, is a diagnostic feature of neurofibromatosis type I, but other features are required to diagnose NF-1.

- Familial multiple café au lait spots have been observed without NF-1 diagnosis.

- They can be caused by vitiligo in the rare McCune–Albright syndrome.

- Legius syndrome

- Tuberous sclerosis

- Fanconi anemia

- Idiopathic

- Ataxia-telangiectasia

- Basal cell nevus syndrome

- Benign congenital skin lesion

- Bloom syndrome

- Chédiak–Higashi syndrome

- Congenital naevus

- Gaucher disease

- Hunter syndrome

- Jaffe–Campanacci syndrome

- Maffucci syndrome

- Multiple mucosal neuroma syndrome

- Noonan syndrome

- Pulmonary Stenosis

- Silver–Russell syndrome

- Watson syndrome

- Wiskott–Aldrich syndrome

In terms of the genetics of Legius syndrome one finds the condition is autosomal dominant in regards to inheritance, and caused by mutations to the SPRED1 gene at chromosome 15, specifically 15q14 (or (GRCh38): 15:38,252,086-38,357,248)

Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I (NF-1), it is caused by mutations in the SPRED1 gene, it is also known as Neurofibromatosis Type 1-like syndrome (NFLS). The condition is a RASopathy, developmental syndromes due to germline mutations in genes

Oculocutaneous Albinism Type I or –Type 1A (OCA1A) is an autosomal recessive skin disease associated with albinism. This type of albinism is caused when the gene OCA1 does not function properly.

The location of OCA1 may be written as "11q1.4-q2.1", meaning it is on chromosome 11, long arm, somewhere in the range of band 1, sub-band 4, and band 2, sub-band 1.

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.

This not known with certainty but is estimated to be about one per million. It appears to be more common in females than males.

Griscelli syndrome type 2 (also known as "partial albinism with immunodeficiency") is a rare autosomal recessive syndrome characterized by variable pigmentary dilution, hair with silvery metallic sheen, frequent pyogenic infections, neutropenia, and thrombocytopenia.

This includes Chediak-Higashi syndrome and Elejalde syndrome (neuroectodermal melanolysosomal disease).

Bruck syndrome is characterized as the combination of arthrogryposis multiplex congenita and osteogenesis imperfecta. Both diseases are uncommon, but concurrence is extremely rare which makes Bruck syndrome very difficult to research. Bruck syndrome is thought to be an atypical variant of osteogenesis imperfecta most resembling type III, if not its own disease. Multiple gene mutations associated with osteogenesis imperfecta are not seen in Bruck syndrome. Many affected individuals are within the same family, and pedigree data supports that the disease is acquired through autosomal recessive inheritance. Bruck syndrome has features of congenital contractures, bone fragility, recurring bone fractures, flexion joint and limb deformities, pterygia, short body height, and progressive kyphoscoliosis. Individuals encounter restricted mobility and pulmonary function. A reduction in bone mineral content and larger hydroxyapatite crystals are also detectable Joint contractures are primarily bilateral and symmetrical, and most prone to ankles. Bruck syndrome has no effect on intelligence, vision, or hearing.

Café au lait spots are usually present at birth, permanent, and may grow in size or increase in number over time.

Cafe au lait spots are themselves benign and do not cause any illness or problems. However, they may be associated with syndromes such as Neurofibromatosis Type 1 and McCune-Albright syndrome.

The size and shape of the spots do not have any meaning or implications with regards to diagnosis of associated syndromes.

Collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital), also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1(II) chain of type II collagen.

Fucosidosis is an extremely rare disorder first described in 1962 in two Italian siblings who showed progressive intellectual disability and neurological deterioration. The disease itself is extremely rare (less than 100 documented cases) only affecting 1:2,000,000, with most cases being occurring in Italy, Cuba, and the southwest U.S. The disease has three different types. Type 1 and 2 are considered severe, and Type 3 being a mild disease. Symptoms are highly variable with mild cases being able to live to within the third or fourth decade. Type 1 and 2 are both linked with mental retardation. Severe cases can develop life-threatening complications early in childhood.

Because the major accumulating glycoconjugate in fucosidosis patients is the blood group H-antigen, it is intriguing to speculate, but the evidence is not clear at this time, that blood type may affect the course of the disease.

The genetics of Bruck syndrome differs from osteogenesis imperfecta. Osteogenesis imperfecta involves autosomal dominant mutations to Col 1A2 or Col 1A2 which encode type 1 procollagen. Bruck syndrome is linked to mutations in two genes, and therefore is divided in two types. Bruck syndrome type 1 is caused by a homozygous mutation in the FKBP10 gene. It encodes FKBP65, an endoplasmic reticulum associated peptidyl-prolyl cis/trans isomerase (PPIase) that functions as a chaperone in collagen biosynthesis. Osteoblasts deficient in FKBP65 have a buildup of procollagen aggregates in the endoplasmic reticulum which reduces their ability to form bone. Furthermore, Bruck syndrome type 1 patients have under-hydroxylated lysine residues in the collagen telopeptide and as a result show diminished hydroxylysylpyridinoline cross-links. Type 2 is caused by a homozygous mutation in the PLOD2 gene. It encodes the enzyme, lysyl hydroxylase 2, which catalyzes hydroxylation of lysine residues in collagen cross-links. PLOD2 is most expressed in active osteoblasts since collagen cross-linking is tissue-specific. Mutation in PLOD2 alters the structure of telopeptide lysyl hydroxylase and prevents fibril formation of collagen type 1. Bone analysis shows the lysine residues of telopeptides in collagen type 1 are under-hydroxylated.

MODY 6 is a form of maturity onset diabetes of the young.

MODY 6 arises from mutations of the gene for the transcription factor referred to as neurogenic differentiation 1. The gene is on chromosome 2 in a region of the p arm known as IDDM7 because it includes genes affecting susceptibility to type 1 diabetes. NeuroD1 promotes transcription of the insulin gene as well as some genes involved in formation of beta cells and parts of the nervous system.

This is also one of the rarer forms of MODY. Only 3 kindreds with mutations causing MODY6 have been identified so far. In both, some of the members had more typical type 2 diabetes rather than MODY, and the reasons for the difference of expression have not been worked out. Most of the family members with diabetes were diagnosed after age 40, but a few required insulin for blood sugar control.

A mutations in a number of genes have been associated with this condition. Mutations associated with FPL have been reported in "LMNA" (lamin A/C), "PPARG" (PPARγ), "AKT2" (AKT serine/threonine kinase 2), "PLIN1" (perilipin-1), and "CIDEC" (cell-death-inducing DFFA-like effector B).

Six types (1-6) have been described. Types 1-5 are inherited in an autosomal dominant fashion.

Type 1 (Kobberling variety, FPL1) is very rare and has only been reported in women to date. Fat loss is confined to the limbs and mostly in the distal parts. Central obesity may be present. Complications include hypertension, insulin resistance and hypertriglyceridemia. The gene causing this condition is not yet known. This form was first described in 1975.

Type 2 (Dunnigan Variety, FPL2) is the most common form and is due to mutations in the LMNA gene. Over 500 cases have been reported to date. Development up to puberty is normal. Fat is then gradually lost in is the limbs and trunk. Fat may accumulate around the face and between the shoulder blades. Insulin resistance is common. Other conditions associated with this condition include acanthosis nigricans, fatty liver, hypertriglyceridemia and polycystic ovary syndrome in women. There is an increased risk of coronary heart disease. Cardiomyopathy and muscular dystrophy may occur rarely. Xanthoma and nail changes may occur.

Type 3 is due to mutations in the PPARG gene. It is rare with approximately 30 cases reported to date. It is similar to type 2 but tends to be milder.

Type 4 is due to mutations in the PLIN1 gene. It is rare with only a small number of cases reported. Fat loss tends to affect the lower limbs and buttocks. Insulin resistance and hypertriglyceridemia occur. Calf muscular hypertrophy may occur.

Type 5 is due to mutations in the AKT2 gene. It has been reported in four patients all members of the same family. Fat loss affects the upper and lower limbs. The patients also suffered from hypertension, insulin resistance and hypertriglyceridemia.

Type 6 due to mutations in the CIDEC gene. It is inherited in an autosomal recessive fashion and has been reported in only one patient to date. Features included fat loss, severe insulin resistance, fatty liver, acanthosis nigricans and diabetes.