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.

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.

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 main diagnostic tools for evaluating FND are X-rays and CT-scans of the skull. These tools could display any possible intracranial pathology in FND. For example, CT can be used to reveal widening of nasal bones. Diagnostics are mainly used before reconstructive surgery, for proper planning and preparation.

Prenatally, various features of FND (such as hypertelorism) can be recognized using ultrasound techniques. However, only three cases of FND have been diagnosed based on a prenatal ultrasound.

Other conditions may also show symptoms of FND. For example, there are other syndromes that also represent with hypertelorism. Furthermore, disorders like an intracranial cyst can affect the frontonasal region, which can lead to symptoms similar to FND. Therefore, other options should always be considered in the differential diagnosis.

Genetic changes are related to the following types of Stickler syndrome:

- Stickler syndrome, COL2A1 (75% of Stickler cases)

- Stickler syndrome, COL11A1

- Stickler syndrome, COL11A2 (non-ocular)

- Stickler syndrome, COL9A1 (recessive variant)

Whether there are two or three types of Stickler syndrome is controversial. Each type is presented here according to the gene involved. The classification of these conditions is changing as researchers learn more about the genetic causes.

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.

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

Three main points in diagnosing thumb hypoplasia are: width of the first web space, instability of the involved joints and function of the thumb. Thorough physical examination together with anatomic verification at operation reveals all the anomalies. An X-ray of the hand and thumb in two directions is always mandatory. When the pediatrician thinks the condition is associated with some kind of syndrome other tests will be done. More subtle manifestations of types I and II may not be recognized, especially when more obvious manifestations of longitudinal radial deficiency in the opposite extremity are present. Therefore, a careful examination of both hands is important.

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.

The diagnosis is based on the following clinical findings:

- microcephaly

- clinodactyly and shortness of index and little fingers

- syndactyly of 2nd & 3rd and 4th & 5th toe

- short palpebral fissures

- esophageal and/or duodenal atresia

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.

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.

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.

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.

There are multiple classifications for the triphalangeal thumb. The reason for these different classifications is the heterogeneity in appearance of the TPT.

The classification according to Wood describes the shape of the extra phalanx: delta (Fig. 4), rectangular or full phalanx (Table 1). With the classification made by Buck-Gramcko a surgical treatment can be chosen (Table 1). Buck-Gramcko differentiates between six different shapes of the extra phalanx and associated malformations.

Table 1: Classifications of Wood and Buck-Gramcko

Syndactyly of the border digits (thumb/index finger or ring/small fingers) is treated at early age to prevent the larger digit from curving towards the smaller digit with growth. Typically, syndactyly of these digits is treated at six months of age. The treatment of syndactyly of the other digits is elective and is more commonly performed when the digits have grown, at 18–24 months of age.

The goals of surgical treatment are: reducing length of the thumb, creating a good functioning, a stable and non deviated joint and improving the position of the thumb if necessary. Hereby improving function of the hand and thumb.

In general the surgical treatment is done for improvement of the thumb function. However, an extra advantage of the surgery is the improvement in appearance of the thumb. In the past, surgical treatment of the triphalangeal thumb was not indicated, but now it is generally agreed that operative treatment improves function and appearance. Because an operation was not indicated in the past, there’s still a population with an untreated triphalangeal thumb. The majority of this population doesn’t want surgery, because the daily functioning of the hand is good. The main obstacle for the untreated patients might not be the diminished function, but the appearance of the triphalangeal thumb.

The timing of surgery differs between Wood and Buck-Gramcko. Wood advises operation between the age of six months and two years, while Buck-Gramcko advises to operate for all indications before the age of six years.

- For TPT types I and II of the Buck-Gramcko classification, the surgical treatment typically consists of removing the extra phalanx and reconstructing the ulnar collateral ligament and the radial collateral ligament if necessary.

- For type III of Buck-Gramcko classification proposable surgical treatments:

- For type IV of Buck-Gramcko classification the surgical treatment typically consists of an osteotomy which reduces the middle phalanx and arthrodesis of the DIP. This gives a shortening of 1 to 1.5 cm. In most cases, this technique is combined with a shortening, rotation and palmar abduction osteotomy at metacarpal level to correct for position and length of the thumb. The extensor tendons and the intrinsic muscles are shortened as well.

- For type V of the Buck-Gramcko classification the surgical treatment proposably consists of a "pollicization". With a pollicization the malpositioned thumb is repositioned, rotated and shortened, the above-described rotation reduction osteotomy of the first metacarpal can be performed as well.

- For type VI of the Buck-Gramcko classification, the surgical treatment typically consists of removing the additional mostly hypoplastic thumb(s). Further procedures of reconstruction of the triphalangeal thumb are performed according to the shape of the extra phalanx as described above.

The presence of porencephalic cysts or cavities can be detected using trans-illumination of the skull of infant patients. Porencephaly is usually diagnosed clinically using the patients and families history, clinical observations, or based on the presence of certain characteristic neurological and physiological features of porencephaly. Advanced medical imaging with computed tomography (CT), magnetic resonance imaging (MRI), or with ultrasonography can be used as a method to exclude other possible neurological disorders. The diagnosis can be made antenatally with ultrasound. Other assessments include memory, speech, or intellect testing to help further determine the exact diagnose of the disorder.

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).

An OI diagnosis can be confirmed through DNA or collagen testing, but in many cases the occurrence of bone fractures with little trauma and the presence of other clinical features such as blue sclera are sufficient for a diagnosis. A skin biopsy can be performed to determine the structure and quantity of type I collagen. DNA testing can confirm the diagnosis, however, it cannot exclude it because not all mutations causing OI are known and/or tested for. OI type II is often diagnosed by ultrasound during pregnancy, where already multiple fractures and other characteristic features may be present. Relative to control, OI cortical bone shows increased porosity, canal diameter, and connectivity in micro-computed tomography.

An important differential diagnosis of OI is child abuse, as both may present with multiple fractures in various stages of healing. Differentiating them can be difficult, especially when no other characteristic features of OI are present. Other differential diagnoses include rickets, osteomalacia, and other rare skeletal syndromes.

Because the circumference of the conjoined fingers is smaller than the circumference of the two separated fingers, there is not enough skin to cover both digits once they are separated at the time of surgery. Therefore, the surgeon must bring new skin into the area at the time of surgery. This is most commonly done with a skin graft (from groin or anterior elbow). Skin can also be used from the back of the hand by mobilizing it (called a "graftless" syndactyly correction), which requires planning over a period of months prior to surgery.

Under the United States federal government, the National Institute of Neurological Disorders and Stroke and National Institute of Health are involved in conducting and supporting research related to normal and abnormal brain and nervous system development. Information gained from the research is used to develop understanding of the mechanism of porencephaly and used to offer new methods of treatment and prevention for developmental brain disorders such as porencephaly.

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 are several treatments available for bleeding due to factor X deficiency, however a specifi FX concentrate is not available (2009).

1. Prothrombin complex concentrate (PCC) supplies FX with a risk of thrombosis.

2. Fresh frozen plasma (FFP): This is relatively inexpensive and readily available. While effective this treatment carries a risk of blood-borne viruses and fluid overload.

3. If vitamin K levels are low, vitamin K can be supplied orally or parenterally.

Treatment of FX deficiency in amyloidosis may be more complex and involve surgery (splenectomy) and chemotherapy.

Several different types of magnetic resonance imaging (MRI) may be employed in diagnosis: MRI without contrast, Gd contrast enhanced T1-weighted MRI (GdT1W) or T2-weighted enhanced MRI (T2W or T2*W). Non-contrast enhanced MRI is considerably less expensive than any of the contrast enhanced MRI scans. The gold standard in diagnosis is GdT1W MRI.

The reliability of non-contrast enhanced MRI is highly dependent on the sequence of scans, and the experience of the operator.