Many of the characteristic facial features result from the premature fusion of the skull bones (craniosynostosis). The head is unable to grow normally, which leads to a high prominent forehead (turribrachycephaly), and eyes that appear to bulge (proptosis) and are wide-set (hypertelorism). In addition, there is an underdeveloped upper jaw (maxillary hypoplasia). About 50 percent of children with Pfeiffer syndrome have hearing loss, and dental problems are also common.

In people with Pfeiffer syndrome, the thumbs and first (big) toes are wide and bend away from the other digits (pollex varus and hallux varus). Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly).

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.

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

Feingold syndrome is marked by various combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and sometimes learning disability or mental retardation.

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.

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

Individuals with Stickler syndrome experience a range of signs and symptoms. Some people have no signs and symptoms; others have some or all of the features described below. In addition, each feature of this syndrome may vary from subtle to severe.

A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This is caused by underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features, called the Pierre Robin sequence, is common in children with Stickler syndrome. Robin sequence includes a U-shaped or sometimes V-shaped cleft palate (an opening in the roof of the mouth) with a tongue that is too large for the space formed by the small lower jaw. Children with a cleft palate are also prone to ear infections and occasionally swallowing difficulties.

Many people with Stickler syndrome are very nearsighted (described as having high myopia) because of the shape of the eye. People with eye involvement are prone to increased pressure within the eye (ocular hypertension) which could lead to glaucoma and tearing or detachment of the light-sensitive retina of the eye (retinal detachment). Cataract may also present as an ocular complication associated with Stickler's Syndrome. The jelly-like substance within the eye (the vitreous humour) has a distinctive appearance in the types of Stickler syndrome associated with the COL2A1 and COL11A1 genes. As a result, regular appointments to a specialist ophthalmologist are advised. The type of Stickler syndrome associated with the COL11A2 gene does not affect the eye.

People with this syndrome have problems that affect things other than the eyes and ears. Arthritis, abnormality to ends of long bones, vertebrae abnormality, curvature of the spine, scoliosis, joint pain, and double jointedness are all problems that can occur in the bones and joints. Physical characteristics of people with Stickler can include flat cheeks, flat nasal bridge, small upper jaw, pronounced upper lip groove, small lower jaw, and palate abnormalities, these tend to lessen with age and normal growth and palate abnormalities can be treated with routine surgery.

Another sign of Stickler syndrome is mild to severe hearing loss that, for some people, may be progressive (see hearing loss with craniofacial syndromes). The joints of affected children and young adults may be very flexible (hypermobile). Arthritis often appears at an early age and worsens as a person gets older. Learning difficulties, not intelligence, can also occur because of hearing and sight impairments if the school is not informed and the student is not assisted within the learning environment.

Stickler syndrome is thought to be associated with an increased incidence of mitral valve prolapse of the heart, although no definitive research supports this.

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.

The Pai Syndrome is a rare subtype of frontonasal dysplasia. It is a triad of developmental defects of the face, comprising midline cleft of the upper lip, nasal and facial skin polyps and central nervous system lipomas. When all the cases are compared, a difference in severity of the midline cleft of the upper lip can be seen. The mild form presents with just a gap between the upper teeth. The severe group presents with a complete cleft of the upper lip and alveolar ridge.

Nervous system lipomas are rare congenital benign tumors of the central nervous system, mostly located in the medial line and especially in the corpus callosum. Generally, patients with these lipomas present with strokes. However, patients with the Pai syndrome don’t. That is why it is suggested that isolated nervous system lipomas have a different embryological origin than the lipomas present in the Pai syndrome. The treatment of CNS lipomas mainly consists of observation and follow up.

Skin lipomas occur relatively often in the normal population. However, facial and nasal lipomas are rare, especially in childhood. However, the Pai syndrome often present with facial and nasal polyps. These skin lipomas are benign, and are therefore more a cosmetic problem than a functional problem.

The skin lipomas can develop on different parts of the face. The most common place is the nose. Other common places are the forehead, the conjunctivae and the frenulum linguae. The amount of skin lipomas is not related to the severity of the midline clefting.

Patients with the Pai syndrome have a normal neuropsychological development.

Until today there is no known cause for the Pai syndrome.

The large variety in phenotypes make the Pai syndrome difficult to diagnose. Thus the incidence of Pai syndrome seems to be underestimated.

This classification is based on the morphologic characteristics of FND, that describes a variety of phenotypes

Both of these classifications are further described in table 1. This table originates from the article ‘Acromelic frontonasal dysplasia: further delineation of a subtype with brain malformations and polydactyly (Toriello syndrome)', Verloes et al.

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).

Stickler syndrome (hereditary progressive arthro-ophthalmopathy) is a group of genetic disorders affecting connective tissue, specifically collagen. Stickler syndrome is a subtype of collagenopathy, types II and XI. Stickler syndrome is characterized by distinctive facial abnormalities, ocular problems, hearing loss, and joint problems. It was first studied and characterized by Gunnar B. Stickler in 1965.

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).

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.

In general there are five types of thumb hypoplasia, originally described by Muller in 1937 and improved by Blauth, Buck-Gramcko and Manske.

- Type I: the thumb is small, normal components are present but undersized. Two muscles of the thumb, the abductor pollicis brevis and opponens pollicis, are not fully developed

. This type requires no surgical treatment in most cases.

- Type II is characterized by a tight web space between the thumb and index finger which restricts movement, poor thenar muscles and an unstable middle joint of the thumb metacarpophalangeal joint. This unstable thumb is best treated with reconstruction of the mentioned structures.

- Type III thumbs are subclassified into two subtypes by Manske. Both involve a less developed first metacarpal and a nearly absent thenar musculature. Type III-A has a fairly stable carpometacarpal joint and type III-B does not. The function of the thumb is poor. Children with type III are the most difficult patients to treat because there is not one specific treatment for the hypoplastic thumb. The limit between pollicization and reconstruction varies. Some surgeons have said that type IIIA is amenable to reconstruction and not type IIIB. Others say type IIIA is not suitable for reconstruction too. Based on the diagnosis the doctor has to decide what is needed to be done to obtain a more functional thumb, i.e. reconstruction or pollicization. In this group careful attention should be paid to anomalous tendons coming from the forearm (extrinsic muscles, like an aberrant long thumb flexor – flexor pollicis longus).

- Type IV is called a pouce flottant, floating thumb. This thumb has a neurovascular bundle which connects it to the skin of the hand. There’s no evidence of thenar muscles and rarely functioning tendons. It has a few rudimentary bones. Children with type IV are difficult to reconstruct. This type is nearly always treated with an index finger pollicization to improve hand function.

- Type V is no thumb at all and requires pollicization.

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

The triphalangeal thumb has a different appearance than normal thumbs. The appearance can differ widely; the thumb can be a longer thumb, it can be deviated in the radio-ulnar plane (clinodactyly), thumb strength can be diminished. In the case of a five fingered-hand it has a finger-like appearance, with the position in the plane of the four fingers, thenar muscle deficiency, and additional length. There is often a combination with radial polydactyly.

Syndactyly can be simple or complex.

- In simple syndactyly, adjacent fingers or toes are joined by soft tissue.

- In complex syndactyly, the bones of adjacent digits are fused. The kangaroo exhibits complex syndactyly.

Syndactyly can be complete or incomplete.

- In complete syndactyly, the skin is joined all the way to the tip of the involved digits.

- In incomplete syndactyly, the skin is only joined part of the distance to the tip of the involved digits.

Complex syndactyly occurs as part of a syndrome (such as Apert syndrome) and typically involves more digits than simple syndactyly.

Fenestrated syndactyly means the skin is joined for most of the digit but in a proximal area there is gap in the syndactyly with normal skin. This type of syndactyly is found in amniotic band syndrome.

Simple syndactyly can be full or partial, and is present at birth (congenital). In early human fetal development, webbing (syndactyly) of the toes and fingers is normal. At about 6 weeks of gestation, apoptosis takes place due to a protein named sonic hedgehog, also known as SHH, which dissolves the tissue between the fingers and toes, and the webbing disappears. In some fetuses, this process does not occur completely between all fingers or toes and some residual webbing remains.

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.

Patients diagnosed with porencephaly display a variety of symptoms, from mild to severe effects on the patient. Patients with severe cases of porencephaly suffer epileptic seizures and developmental delays, whereas patients with a mild case of porencephaly display little to no seizures and healthy neurodevelopment. Infants with extensive defects show symptoms of the disorder shortly after birth, and the diagnosis is usually made before the age of 1.

The following text lists out common signs and symptoms of porencephaly in affected individuals along with a short description of certain terminologies.

Collagen improperly formed, enough collagen is made but it is defective.

- Bones fracture easily, sometimes even before birth

- Bone deformity, often severe

- Respiratory problems possible

- Short stature, spinal curvature and sometimes barrel-shaped rib cage

- Triangular face

- Loose joints (double-jointed)

- Poor muscle tone in arms and legs

- Discolouration of the sclera (the 'whites' of the eyes are blue)

- Early loss of hearing possible

Type III is distinguished among the other classifications as being the "progressive deforming" type, wherein a neonate presents with mild symptoms at birth and develops the aforementioned symptoms throughout life. Lifespans may be normal, albeit with severe physical handicapping.

Collagen quantity is sufficient but is not of a high enough quality

- Bones fracture easily, especially before puberty

- Short stature, spinal curvature, and barrel-shaped rib cage

- Bone deformity is mild to moderate

- Early loss of hearing

Similar to Type I, Type IV can be further subclassified into types IVA and IVB characterized by absence (IVA) or presence (IVB) of dentinogenesis imperfecta.

Porencephaly is a rare disorder. The exact prevalence of porencephaly is not known; however, it has been reported that 6.8% of patients with cerebral palsy or 68% of patients with epilepsy and congenital vascular hemiparesis have porencephaly. Porencephaly has a number of different, often unknown, causes including absence of brain development and destruction of brain tissue. With limited research, the most commonly regarded cause of porencephaly is disturbances in blood circulation, ultimately leading to brain damage. However, a number of different and multiple factors such as abnormal brain development or damage to the brain tissue can also affect the development of porencephaly.

The following text lists out potential risk factors of developing porencephaly and porencephalic cysts and cavities along with brief description of certain terminologies.

Cysts or cavities can occur anywhere within the brain and the locations of these cysts depend highly on the patient. Cysts can develop in the frontal lobe, parietal lobe, forebrain, hindbrain, temporal lobe, or virtually anywhere in the cerebral hemisphere.

Symptoms may differ greatly, as apparently modifiers control to some degree the amount of FX that is produced. Some affected individuals have few or no symptoms while others may experience life-threatening bleeding. Typically this bleeding disorder manifests itself as a tendency to easy bruising, nose bleeding, heavy and prolonged menstruation and bleeding during pregnancy and childbirth, and excessive bleeding after dental or surgical interventions. Newborns may bleed in the head, from the umbilicus, or excessively after circumcision. Other bleeding can be encountered in muscles or joints, brain, gut, or urine

While in congenital disease symptoms may be present at birth or show up later, in patients with acquired FX deficiency symptoms typically show up in later life.

Bernard–Soulier syndrome often presents as a bleeding disorder with symptoms of: