Cardiofaciocutaneous Syndrome (CFC syndrome) is an extremely rare and serious genetic disorder.

It is characterized by the following:

- Distinctive facial appearance

- Unusually sparse, brittle, curly scalp hair

- A range of skin abnormalities from dermatitis to thick, scaly skin over the entire body (generalized ichthyosis)

- Heart malformations (congenital or appearing later) especially an obstruction of the normal flow of blood from the lower right ventricle of the heart to the lungs (valvar pulmonary stenosis)

- Delayed growth

- Foot abnormalities (extra toe or fusion of two or more toes)

Approximately 100 cases have been described in the literature to date.

The facial features are characteristic and include

- Deep set eyes

- Strabismus

- Myopia

- Marked nasal root

- Broad and/or beaked nasal bridge

- Prominent Cupid's bow

- Everted lower lip

- Tented upper lip

- Large mouth

- Widely spaced teeth

- Wide and shallow palate

- Ears with thick and overfolded helix

Most have a smiling appearance.

Intellectual disability is severe. Language is absent or limited to only a few words. Stereotypic movements particularly of the arms, wrists and fingers is almost universal. Hypotonia is common (75%) as is an unsteady gait. All have delayed walking. Other features include a single (simian) palmar crease, long, slender fingers, flat feet and cryptorchidism (in males). Finger clubbing and the presence of fetal pads is common. Hyperventilation occurs in over half and is frequently followed by apnea and cyanosis. During these episodes aerophagia may occur. Constipation is common. Microcephaly and seizures may occur. Hypopigmented skin macules have occasionally been reported.

Nablus mask-like facial syndrome is a microdeletion syndrome triggered by a deletion at chromosome 8 q22.1 that causes a mask-like facial appearance in those affected.

It is characterized by a narrowing of the eyes, tight, glistening facial skin, and a flat, broad nose. Other features of the syndrome include malformed ears, unusual hair patterns on the scalp, bent fingers and toes and joint deformities in the hands and feet, unusual teeth, mild developmental delay, cryptorchidism, and a generally happy disposition. It is a rare genetic disorder by inheritance found in Palestinian people named after Nablus city in the West Bank. It is part of many new genetic disorders of newborns that is increasing exponentially in Arabs in recent years as reported by Centre for Arab Genomic Studies in Dubai.

Melkersson–Rosenthal syndrome (also termed "Miescher-Melkersson-Rosenthal syndrome"), is a rare neurological disorder characterized by recurring facial paralysis, swelling of the face and lips (usually the upper lip - cheilitis granulomatosis) and the development of folds and furrows in the tongue (fissured tongue). Onset is in childhood or early adolescence. After recurrent attacks (ranging from days to years in between), swelling may persist and increase, eventually becoming permanent. The lip may become hard, cracked, and fissured with a reddish-brown discoloration. The cause of Melkersson–Rosenthal syndrome is unknown, but there may be a genetic predisposition. It has been noted to be especially prevalent among certain ethnic groups in Bolivia. It can be symptomatic of Crohn's disease or sarcoidosis. Approximately 400 cases have been reported worldwide.

Individuals with the disorder usually have distinctive malformations of the craniofacial area including an unusually large head (macrocephaly), prominent forehead, and abnormal narrowing of both sides of the forehead (bitemporal constriction); The nose can be upturned and short with a low nasal bridge; and large ears that are abnormally rotated toward the back of the head. In many cases, affected individuals also have downward slanting eyelid folds, widely spaced eyes, drooping of the upper eyelids, inward deviation of the eyes, and other eye abnormalities including absent eyebrows and eyelashes.

Below are the common clinical features of those diagnosed with Floating–Harbor syndrome. Patients will show varying degrees of some or all FHS symptoms. Facial abnormalities are the most defining aspects of those diagnosed with this disease.

Keppen–Lubinsky syndrome (KPLBS) is an extremely rare congenital disorder.The minimal clinical criteria for the Keppen–Lubinsky syndrome are as follows: normal growth parameters at birth, postnatal growth failure, peculiar face with an aged appearance (large prominent eyes, a narrow nasal bridge, a tented upper lip, a high palate, an open mouth), skin tightly adherent to facial bones, generalized lipodystrophy, microcephaly, and development delay. Keppen-Lubinsky syndrome is caused by mutation in the inwardly rectifying K+ channels encoded by KCNJ6 gene.

The joint changes include hyperextensibility (double-jointedness) and arthritis. Babies and young children with Stickler syndrome usually have very hyperextensible joints. As an affected child gets older, they may experience pain and stiffness from overuse of a joint. Osteoarthritis of the large joints often develops during the third or fourth decade. The joint changes in Marshall syndrome are of the same type but to a lesser degree. There also may be changes in the bones that show up on X-ray but generally are not a problem.

The differential diagnosis of broad thumbs includes Rubinstein-taybi syndrome, where they are a cardinal feature. FHS is also in the differential, which logically agrees with the thought that the disease is a result of a mutation in SRCAP, as this gene interacts with CBP.

SFMS affects the skeletal and nervous system. This syndrome's external signs would be an unusual facial appearance with their heads being slightly smaller and unusually shaped, a narrow face which is also called dolichocephaly, a large mouth with a drooping lower lip that are held open, protruding upper jaw, widely spaced upper front teeth, an underdeveloped chin, cleft palate and exotropied-slanted eyes with drooping eyelids.

Males who have SFMS have short stature and a thin body build. Also skin is lightly pigmented with multiple freckles. They may have scoliosis and chest abnormalities.

Affected boys have reduced muscle tone as infants and young children. X-rays sometimes show that their bones are underdeveloped and show characteristics of younger bones of children. Boys usually under the age of 10 have reduced muscle tone but later, patients with SFMS over the age of 10 have increased muscle tone and reflexes that cause spasticity. Their hands are short with unusual palm creases with short, shaped fingers and foot abnormalities are shortened and have fused toes and usually mild.

They have an absent of a spleen and the genitals may also show undescended testes ranging from mild to severe that leads to female gender assignment.

People who have SFMS have severe mental retardation. They are sometimes restless, behavior problems, seizures and severe delay in language development. They are self-absorbed with reduced ability to socialize with others around them. They also have psychomotor retardation which is the slowing-down of thoughts and a reduction of physical movements. They have cortical atrophy or degeneration of the brain's outer layer. Cortical atrophy is usually founded in older affected people.

Melkersson–Rosenthal syndrome may recur intermittently after its first appearance. It can become a chronic disorder. Follow-up care should exclude the development of Crohn's disease or sarcoidosis.

The clinical presentation is variable but includes

- developmental and growth delay

- athletic muscular built

- skeletal anomalies

- joint stiffness

- characteristic facial appearance

- deafness

- variable cognitive deficits

- tracheal stenosis

- aortic stenosis

- pyloric stenosis

The facial abnormalities include:

- blepharophimosis (an abnormally narrow gap between the upper and lower eyelids)

- maxillary hypoplasia (underdevelopment of the upper jaw)

- prognathism (prominent lower jaw)

The skeletal abnormalities include:

- short stature

- square body shape

- broad ribs

- iliac hypoplasia

- brachydactyly

- flattened vertebrae

- thickened calvaria

Congenital heart disease and undescended testes have also been reported in association with this syndrome.

Nasodigitoacoustic syndrome is congenital and is characterized by a number of nasal, facial and cranial features. These include a broad and high, sometimes depressed nasal bridge (top of the nose, between the eyes) and a flattened nasal tip. This can give the nose a shortened, arch-like appearance. Hypertelorism (unusually wide-set eyes), prominent frontal bones and supraorbital ridge (the eyebrow ridge), bilateral epicanthic folds (an extra flap of skin over the eyelids), a broad forehead and an overall enlarged head circumference have also been observed. A bulging of the upper lip with an exaggerated cupid's bow shape, and maxillary hypoplasia (underdevelopment of the upper jaw) with retraction have also been reported.

Several anomalies affecting the digits (fingers and toes) have been observed with the syndrome. A broadening of the thumbs and big toes (halluces) was reported in two brothers. The broadening was apparent in all distal phalanges of the fingers, although the pinkies were unaffected yet appeared to be clinodactylic (warped, or bent toward the other fingers). Additional eports described this broadness of the thumbs and big toes, with brachydactyly (shortness) in the distal phalanges of the other digits except the pinkies in affected individuals. On X-rays of a two-year-old boy with the disorder, the brachydactyly was shown to be caused by shortening of epiphyses (joint-ends) of the distal phalanges. The broadness and brachydactyly of the big toes in particular may give them a stunted, rounded and stub-like appearance.

The auditory, or "acoustic" abnormalities observed with the syndrome include sensorineural hearing loss and hoarseness. Two affected Turkish brothers with a mild form of this hearing loss, and a hoarse voice were reported. A laryngoscopic examination of both brothers revealed swelling of the vocal cords, and a malformed epiglottis. Sensorineural-associated hearing impairment and hoarsness was also observed in a 10-year-old girl and her father, and in a number of other cases.

Other characteristics seen with the syndrome include developmental delay, growth retardation, pulmonary stenosis (an obstruction of blood-flow from the right ventricle of the heart to the pulmonary artery) with associated dyspnea (shortness of breath), and renal agenesis (failure of the kidneys to develop during the fetal period). Undescended testes, hyperactivity and aggressive behavior have also been noted.

The most severe problem associated with Stickler syndrome is Pierre Robin syndrome. This refers to a cleft palate resulting from a very small lower jaw. During early fetal life, the roof of the mouth is normally open and the sides of the palate have to come together to close. If the jaw is too small, there is not enough room for the tongue which is then pushed up and gets in the way of the closing palate. Sometimes the chin is so small the baby has problems with eating and breathing if the tongue blocks the back of the throat. Cleft palate is found less frequently in Marshall Syndrome than in Stickler syndrome but still more frequently than in the general population.

The facial features of Marshall Syndrome include a flat midface, the appearance of large eyes, short upturned nose, and a round face. The facial features of Stickler syndrome are less prominent but include a rather long flat face, and depressed nasal bridge.

Pitt–Hopkins syndrome is a rare genetic disorder characterized by developmental delay, a wide mouth, distinctive facial features, and intermittent hyperventilation followed by apnea. It is associated with an abnormality within chromosome 18: specifically, it is caused by an insufficient expression of the TCF4 gene.

Fissured tongue is seen in Melkersson-Rosenthal syndrome (along with facial nerve paralysis and granulomatous cheilitis). It is also seen in most patients with Down syndrome, in association with geographic tongue, in patients with oral manifestations of psoriasis, and in healthy individuals. Fissured tongue is also sometimes a feature of Cowden's syndrome.

Gerodermia osteodysplastica is characterized by symptoms and features which affect the connective tissues, skin and skeletal system.

These are: wrinkly, loose skin over the face, abdomen, and extremites (hands, feet) on the dorsal sides usually worsened by chronic joint laxity and hyperextensibility; fragmented elastic fibers of the skin that are reduced in number, with disorientation of collagen fibers; osteopenia and osteoporosis, with associated fractures; malar hypoplasia (underdeveloped cheek bone), maxillary hypoplasia (underdeveloped upper jaw), mandibular prognathism (protrusion of the lower jaw and chin), bowed long bones, platyspondyly (flattened spine) related to vertebral collapse; kyphoscoliosis (scoliosis with kyphosis, or "hunch back"), metaphyseal peg (an unusual outgrowth of metaphyseal tissue which protrudes into the epiphyseal region of the bone, near the knee); and the overall physical effects and facial appearance of dwarfism with premature aging.

Other features and findings include: intrauterine growth retardation, congenital hip dislocations, winged scapulae (shoulder blades), pes planus (fallen arches), pseudoepiphyses of the second metacarpals (upper bone of the fingers), hypotelorism (close-set eyes), malformed ears,

developmental delay,

failure to thrive and abnormal electroencephalograph (EEG) readings.

Dental and orthodontal abnormalities in addition to maxillary hypoplasia and mandibular prognathism have also been observed in gerodermia osteodysplastica. Including malocclusion of the dental arches (the maxilla and mandible), radiological findings in some cases have indicated significant overgrowth of the mandibular premolar and molar roots;

hypercementosis (overproduction of cementum) of the molars and maxillary incisors; enlarged, funnel-shaped mandibular lingula (spiny structures on the ramus of the mandible); and a radiolucent effect on portions of many teeth, increasing their transparency to x-rays.

One of the most prominent and visible symptoms of Nevo Syndrome is the prenatal overgrowth, which continues into the infant and toddler stage. This excessive weight gain can be attributed to the low concentrations of growth hormone and insulin growth factor that are normally present to regulate weight gain. Other common symptoms associated with Nevo Syndrome are the outward wrist-drop, edema in hands and feet, undescended testes, low-set ears, hypotonia, the presence of low muscle tone in children, and long tapered fingers, and a highly arched palate.

All of the following are usual elements of the syndrome:

- Short stature

- Abnormal calf bone shape (fibula)

- Unusual facial appearance

- Polycystic kidneys

- Abnormally long fibula

- Mild sunken chest

- Large corneas

- Inguinal hernia

- Umbilical hernia

This syndrome is associated with microcephaly, arthrogryposis and cleft palate and various craniofacial, respiratory, neurological and limb abnormalities, including bone and joint defects of the upper limbs, adducted thumbs, camptodactyly and talipes equinovarus or calcaneovalgus. It is characterized by craniosynostosis, and myopathy in association with congenital generalized hypertrichosis.

Patients with the disease are considered intellectually disabled. Most die in childhood. Patients often suffer from respiratory difficulties such as pneumonia, and from seizures due to dysmyelination in the brain's white matter. It has been hypothesized that the Moro reflex (startle reflex in infants) may be a tool in detecting the congenital clapsed thumb early in infancy. The thumb normally extends as a result of this reflex.

This syndrome is characterised by typical facial appearance, slight build, thin and translucent skin, severely adducted thumbs, arachnodactyly, club feet, joint instability, facial clefting and bleeding disorders, as well as heart, kidney or intestinal defects. Severe psychomotor and developmental delay and decreased muscle tone may also be present during infancy. Cognitive development during childhood is normal.

Patients with Sack–Barabas syndrome have thin, fragile skin, especially in the chest and abdomen, that bruises easily; hands and feet may have an aged appearance. Skin is soft but not overly stretchy.

Facial features are often distinctive, including protruding eyes, a thin nose and lips, sunken cheeks, and a small chin.

Other signs of the disorder include hypermobility of joints, tearing of tendons and muscles, painfully swollen veins in the legs, lung collapse, and slow wound healing following injury or surgery.

Infants with the condition may be born with hip dislocations and clubfeet.

Unpredictable ruptures of arteries and organs are serious complications of SBS. Ruptured arteries can cause internal bleeding, stroke, or shock, the most common cause of death in patients with this disorder.

Rupture of the intestine is seen in 25 to 30 percent of affected individuals and tearing of the uterus during pregnancy affects 2 to 3 percent of women. Although these symptoms are rare in childhood, more than 80 percent of patients experience severe complications by the age of 40. Teenage boys are at high risk for arterial rupture, often being fatal.

Exner syndrome is sometimes misdiagnosed as interstitial cystitis in its very early stages, but once the fibula begins to malform, Exner is the only real diagnosis.

Pashayan syndrome also known as Pashayan–Prozansky Syndrome, and blepharo-naso-facial syndrome is a rare syndrome. Facial abnormalities characterise this syndrome as well as malformation of extremities. Specific characteristics would be a bulky, flattened nose, where the face has a mask like appearance and the ears are also malformed.

A subset of Pashayan syndrome has also been described, known as "cerebrofacioarticular syndrome", "Van Maldergem syndrome'" or "Van Maldergem–Wetzburger–Verloes syndrome". Similar symptoms are noted in these cases as in Pashayan syndrome.

The clinical appearance is considerably varied in both the orientation, number, depth and length of the fissure pattern. There are usually multiple grooves/furrows 2–6 mm in depth present. Sometimes there is a large central furrow, with smaller fissures branching perpendicularly. Other patterns may show a mostly dorsolateral position of the fissures (i.e. sideways running grooves on the tongue's upper surface). Some patients may experience burning or soreness.