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.

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.

Overall, the estimated prevalence of Stickler syndrome is about 1 in 10,000 people. Stickler syndrome affects 1 in 7,500 to 9,000 newborns.

Many professionals that are likely to be involved in the treatment of those with Stickler's syndrome, include anesthesiologists, oral and maxillofacial surgeons; craniofacial surgeons; ear, nose, and throat specialists, ophthalmologists, optometrists, audiologists, speech pathologists, physical therapists and rheumatologists.

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

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.

There is still some discussion on whether FND is sporadic or genetic. The majority of FND cases are sporadic. Yet, some studies describe families with multiple members with FND. Gene mutations are likely to play an important role in the cause. Unfortunately, the genetic cause for most types of FND remains undetermined.

OAFNS is a combination of FND and oculo-auriculo-vertebral spectrum (OAVS).

The diagnosis of OAVS is based on the following facial characteristics: microtia (underdeveloped external ear), preauricular tags, facial asymmetry, mandibular hypoplasia and epibulbar lipodermoids (benign tumor of the eye which consists of adipose and fibrous tissue).

There still remains discussion about the classification and the minimal amount of characteristics. When someone presents with FND and the characteristics of OAVS, the diagnosis OAFNS may be made.

As the incidence of OAFNS is unknown, there are probably a lot of children with mild phenotypes that aren’t being diagnosed as being OAFNS.

The cause of OAFNS is unknown, but there are some theories about the genesis. Autosomal recessive inheritance is suggested because of a case with two affected siblings and a case with consanguineous parents. However, another study shows that it is more plausible that OAFNS is sporadic.

It is known that maternal diabetes plays a role in developing malformations of craniofacial structures and in OAVS. Therefore, it is suggested as a cause of OAFNS. Folate deficiency is also suggested as possible mechanism.

Low-dose CT protocols should be considered in diagnosing children with OAFNS.

Feingold syndrome is caused by mutations in the neuroblastoma-derived V-myc avian myelocytomatosis viral-related oncogene (MYCN) which is located on the short arm of chromosome 2 (2p24.1).

Somatic mutations in the PIK3CA have been identified as a cause of CLOVES syndrome. PIK3CA is a protein involved in the PI3K-AKT signalling pathway. Mutations in other parts of this pathway cause other overgrowth syndromes including proteus syndrome and hemimegaencephaly.

Feingold syndrome (also called oculodigitoesophagoduodenal syndrome) is a rare autosomal dominant hereditary disorder. It is named after Murray Feingold, an American physician who first described the syndrome in 1975. Until 2003, at least 79 patients have been reported worldwide.

CLOVES syndrome is an extremely rare overgrowth syndrome, with complex vascular anomalies. CLOVES syndrome affects people with various symptoms, ranging from mild fatty soft-tissue tumors to vascular malformations encompassing the spine or internal organs. CLOVES syndrome is closely linked to other overgrowth disorders like proteus syndrome, Klippel–Trénaunay syndrome, Sturge–Weber syndrome, and hemihypertrophy, to name a few.

'CLOVES' is an acronym for:

- C is for congenital.

- L is for lipomatous, which means pertaining to or resembling a benign tumor made up of mature fat cells. Most CLOVES patients present with a soft fatty mass at birth, often visible on one or both sides of the back, legs and/or abdomen.

- O is for overgrowth, because there is an abnormal increase in the size of the body or a body part that is often noted at birth. Patients with CLOVES may have affected areas of their bodies that grow faster than in other people. Overgrowth of extremities (usually arms or legs) is seen, with large wide hands or feet, large fingers or toes, wide space between fingers, and asymmetry of body parts.

- V is for vascular malformations, which are blood vessel abnormalies. Patients with CLOVES have different venous, capillary, and lymphatic channels - typically capillary, venous and lymphatic malformations are known as "slow flow" lesions. Some patients with CLOVES have combined lesions (which are fast flow) and some have aggressive vascular malformation known as arteriovenous malformations (AVM). The effect of a vascular malformation varies per patient based on the type, size, and location of the malformation, and symptoms can vary.

- E is for Epidermal naevi, which are sharply-circumscribed chronic lesions of the skin, and benign. These are often flesh-colored, raised or warty.

- S is for Spinal/Skeletal Anomalies or scoliosis. Some patients with CLOVES have tethered spinal cord, vascular malformations in or around their spines, and other spinal differences. High-flow aggressive spinal lesions (like AVM) can cause serious neurological deficits/paralysis.

The syndrome was first recognised by Saap and colleagues who recognised the spectrum of symptoms from a set of seven patients. In this initial description the syndrome is named CLOVE syndrome. It is believed that the first description of a case of CLOVES syndrome was written by Hermann Friedberg, a German physician, in 1867.

Triphalangeal thumb can occur in syndromes but it can also be isolated. The triphalangeal thumb can appear in combination with other malformations or syndromes.

Syndromes include:

- Holt-Oram syndrome

- Aase syndrome

- Blackfan-Diamond syndrome

- Townes-Brocks syndrome

Malformations include:

- Radial polydactyly

- Syndactyly

- Claw-like hand or foot

LIG4 syndrome (also known as Ligase IV syndrome) is an extremely rare condition caused by mutations in the DNA Ligase IV (LIG4) gene. Some mutations in this gene are associated with a resistance against multiple myeloma and Severe Combined Immunodeficiency. Severity of symptoms depends on the degree of reduced enzymatic activity of Ligase IV or gene expression.

As DNA ligase IV is essential in V(D)J recombination, the mechanism by which immunoglobulins, B cell and T cell receptors are formed, patients with LIG4 syndrome may suffer from less effective or defective V(D)J recombination. Some patients have a severe immunodeficiency characterized by pancytopenia, causing chronic respiratory infections and sinusitis. Clinical features also include Seckel syndrome-like facial abnormalities and microcephaly. Patients also suffer from growth retardation and skin conditions, including photosensitivity, psoriasis and telangiectasia. Although not present in all, patients may also present with hypothyroidism and type II diabetes and possibly malignancies such as acute T-cell leukemia. The clinical phenotype of LIG4 syndrome closely resembles that of Nijmegen breakage syndrome (NBS).

Malformations of the upper extremities can occur In the third to seventh embryonic week. In some cases the TPT is hereditary. In these cases, there is a mutation on chromosome 7q36. If the TPT is hereditary, it is mostly inherited as an autosomal dominant trait, non-opposable and bilateral. The sporadic cases are mostly opposable and unilateral.

Thumb hypoplasia is a spectrum of congenital abnormalities of the thumb varying from small defects to absolute retardation of the thumb. It can be isolated, when only the thumb is affected, and in 60% of the cases it is associated with radial dysplasia (or radial club, radius dysplasia, longitudinal radial deficiency). Radial dysplasia is the condition in which the forearm bone and the soft tissues on the thumb side are underdeveloped or absent.

In an embryo the upper extremities develop from week four of the gestation. During the fifth to eighth week the thumb will further develop. In this period something goes wrong with the growth of the thumb but the exact cause of thumb hypoplasia is unknown.

One out of every 100,000 live births shows thumb hypoplasia. In more than 50% of the cases both hands are affected, otherwise mainly the right hand is affected.

About 86% of the children with hypoplastic thumb have associated abnormalities. Embryological hand development occurs simultaneously with growth and development of the cardiovascular, neurologic and hematopoietic systems. Thumb hypoplasia has been described in 30 syndromes wherein those abnormalities have been seen. A syndrome is a combination of three or more abnormalities. Examples of syndromes with an hypoplastic thumb are Holt-Oram syndrome, VACTERL association and thrombocytopenia absent radius (TAR syndrome).

When it comes to treatment it is important to differentiate a thumb that needs stability, more web width and function, or a thumb that needs to be replaced by the index finger. Severe thumb hypoplasia is best treated by pollicization of the index finger. Less severe thumb hypoplasia can be reconstructed by first web space release, ligament reconstruction and muscle or tendon transfer.

It has been recommended that pollicization is performed before 12 months, but a long-term study of pollicizations performed between the age of 9 months and 16 years showed no differences in function related to age at operation.

It is important to know that every reconstruction of the thumb never gives a normal thumb, because there is always a decline of function. When a child has a good index finger, wrist and fore-arm the maximum strength of the thumb will be 50% after surgery in comparison with a normal thumb. The less developed the index finger, wrist and fore-arm is, the less strength the reconstructed thumb will have after surgery.

Five types of syndactyly have been identified in humans. The corresponding loci associated with these types and their common phenotypical expression are as follows:

- "type I": 2q34-q36; webbing occurs between middle and ring fingers and/or second and third toes.

- "type II": 2q31; also involves long and ring fingers, but has a sixth finger merged in between.

- "type III": 6q21-q23; small finger is merged into the ring finger.

- "type IV": 7q36; involves all fingers and/or toes.

- "type V": 2q31-q32; similar to type I, but the metacarpals and metatarsals may also be fused.

The most common problem with syndactyly correction is creeping of the skin towards the fingertip over time. This is likely due to tension at the site of the repair between the digits. Additional surgery may be required to correct this. One critique of using skin grafts is that the grafts darken in the years after surgery and become more noticeable. Also, if the skin grafts are harvested from the groin area, the skin may grow hair. Finally, the fingers may deviate after surgery. This is most commonly seen in complex syndactyly (when there has been a bony joining of the fingers).

In utero exposure to cocaine and other street drugs can lead to porencephaly.

From recent studies, de novo and inherited mutations in the gene "COL4A1", suggesting genetic predisposition within the family, that encodes type IV collagen α1 chain has shown to be associated with and present in patients with porencephaly. "COL4A1" mutation causes a variety of phenotypes, including porencephaly, infantile hemiplegia, and cerebral small vessel diseases involving both stroke and infarction. Abnormal gene expression of "COL4A1" can contribute to the development of porencephaly. "COL4A1" gene expresses a type IV collagen (basement protein) that is present in all tissue and blood vessels and is extremely important for the structural stability of vascular basement membranes. The "COL4A1" protein provides a strong layer around blood vessels. The mutation can weaken the blood vessels within the brain, elevating the probability of a hemorrhage, and eventually promoting internal bleeding then leading to porencephaly during neurodevelopment of infantile stage. Therefore, the formation of cavities can be a result of hemorrhages which promote cerebral degeneration. In a mouse model, mouse with "COL4A1" mutations displayed cerebral hemorrhage, porencephaly, and abnormal development of vascular basement membranes, such as uneven edges, inconsistent shapes, and highly variable thickness. Purposely causing a mutation in the "COL4A1" gene caused several mouse to develop cerebral hemorrhage and porencephaly-like diseases. Though, there is no direct correlation between mutations of the "COL4A1" gene, it appears that it has an influential effect on the development of porencephaly.

Another genetic mutation, "factor V G1691A" mutation, has been reported to show possible association to the development of porencephaly. A mutation in "factor V G1691A" increases the risk of thrombosis, blood clots, in neonates, infants, and children. Therefore, 76 porencephalic and 76 healthy infants were investigated for "factor V G1691A" mutation along with other different prothrombotic risk factors. The results indicated that there was higher prevalence of the "factor V G1691A" mutation in the porencephalic patient group. The prediction that childhood porencephaly is caused by hypercoagulable state, a condition where one has a higher chance of developing blood clots, was supported by the significance of the "factor V G1691A" mutation. Also, pregnant women in hypercoagulable state can cause the fetus to have the same risks, therefore possibly causing fetal loss, brain damage, lesions, and infections that lead to porencephaly. However, other different prothrombotic risk factors individually did not reach statistical significance to link it to the development of porencephaly, but a combination of multiple prothrombotic risk factors in the porencephaly group was significant. Overall, "factor V G1691A" mutation has been linked to the development of porencephaly. However, this one mutation is not the cause of porencephaly, and whether further prothrombiotic risk factors are associated with porencephaly still remains unknown.

More than 1 in 2 people with OI also have dentinogenesis imperfecta (DI) - a congenital disorder of formation of dentine. Dental treatment may pose as a challenge as a result of the various deformities, skeletal and dental, due to OI. Children with OI should go for a dental check-up as soon as their teeth erupt, this may minimize tooth structure loss as a result of abnormal dentine, and they should be monitored regularly to preserve their teeth and oral health.

There is no known prevention of spinocerebellar ataxia. Those who are believed to be at risk can have genetic sequencing of known SCA loci performed to confirm inheritance of the disorder.

Inherited or congenital FX deficiency is passed on by autosomal recessive inheritance. A person needs to inherit a defective gene from both parents. People who have only one defective gene usually do not exhibit the disease, but can pass the gene on to half their offspring. Different genetic mutations have been described.

In persons with congenital FX deficiency the condition is lifelong. People affected should alert other family members as they may also have the condition or carry the gene. In the general population the condition affects about 1 in 1 million people. However, the prevalence may be higher as not all individuals may express the disease and be diagnosed.

In the acquired form of FX deficiency an insufficient amount of factor X is produced by the liver due to liver disease, vitamin K deficiency, buildup of abnormal proteins in organs (amyloidosis) or certain medications (i.e. warfarin). In amyloidosis FX deficiency develops as FX and other coagulation factors are absorbed by amyloid fibrils.

With adaptive equipment such as crutches, wheelchairs, splints, grabbing arms, or modifications to the home, many individuals with OI can maintain a significant degree of autonomy.