The classical triad of symptoms that defines 3C syndrome includes certain heart defects, hypoplasia (underdevelopment) of the cerebellum, and cranial dysmorphisms, which can take various forms. The heart defects and cranial dysmorphisms are heterogeneous in individuals who are all classed as having Ritscher-Schinzel syndrome.

Heart defects commonly seen with Ritscher-Schinzel syndrome are associated with the endocardial cushion and are the most important factor in determining a diagnosis. The mitral valve and tricuspid valve of the heart can be malformed, the atrioventricular canal can be complete instead of developing into the interatrial septum and interventricular septum, and conotruncal heart defects, which include tetralogy of Fallot, double outlet right ventricle, transposition of the great vessels, and hypoplastic left heart syndrome. Aortic stenosis and pulmonary stenosis have also been associated with 3C syndrome.

The cranial dysmorphisms associated with 3C syndrome are heterogeneous and include a degree of macrocephaly, a large anterior fontanel, a particularly prominent occiput and forehead, ocular hypertelorism (wide-set eyes), slanted palpebral fissures, cleft palate, a depressed nasal bridge, cleft palate with associated bifid uvula, low-set ears, micrognathia (an abnormally small jaw), brachycephaly (flattened head), and ocular coloboma. Low-set ears are the most common cranial dysmorphism seen in 3C syndrome, and ocular coloboma is the least common of the non-concurrent symptoms (cleft lip co-occurring with cleft palate is the least common).

Cranial dysplasias associated with 3C syndrome are also reflected in the brain. Besides the cerebellar hypoplasia, cysts are commonly found in the posterior cranial fossa, the ventricles and the cisterna magna are dilated/enlarged, and Dandy-Walker malformation is present. These are reflected in the developmental delays typical of the disease. 75% of children with 3C syndrome have Dandy-Walker malformation and hydrocephalus.

Signs and symptoms in other body systems are also associated with 3C syndrome. In the skeletal system, ribs may be absent, and hemivertebrae, syndactyly (fusion of fingers together), and clinodactyly (curvature of the fifth finger) may be present. In the GI and genitourinary systems, anal atresia, hypospadia (misplaced urethra), and hydronephrosis may exist. Adrenal hypoplasia and growth hormone deficiency are associated endocrine consequences of Ritscher-Schinzel syndrome. Some immunodeficiency has also been reported in connection with 3C syndrome.

Many children with the disorder die as infants due to severe congenital heart disease. The proband of Ritscher and Schinzel's original study was still alive at the age of 21.

A fetus with 3C syndrome may have an umbilical cord with one umbilical artery instead of two.

In addition to small palpebral fissures, features include epicanthus inversus (fold curving in the mediolateral direction, inferior to the inner canthus), low nasal bridge, ptosis of the eyelids and telecanthus.

Blepharophimosis syndrome is an autosomal dominant characterized by blepharophimosis (horizontal shortening of the palpebral fissures), ptosis (upper eyelid drooping, usually with the characteristics of congenital ptosis), epicanthus inversus (skin folds by the nasal bridge, more prominent lower than upper lid), and telecanthus (widening of the distance between the medial orbital walls). This syndrome is caused by mutations in the FOXL2 gene, either with premature ovarian failure (BPES type I) or without (BPES type II). It may also be associated with lop ears, ectropion, hypoplasia of superior orbital rims, and hypertelorism.

Clinical diagnosis based on orofacial clefts and lip pits typically occurs shortly after birth. Certain defects may be difficult to diagnose, particularly a submucous cleft palate. This form of CP may not be detected except through finger palpation, as the mucosa covering the palate is intact, but the muscles underneath have lost their proper attachments. Feeding problems, impaired speech, and hearing loss are symptoms of a submucous cleft palate. Furthermore, approximately 15% of VWS cases with orofacial clefts, in the absence of prominent lip pits, cannot be easily distinguished from non-syndromic forms of orofacial clefting. Therefore, it is very important to closely examine these patients as well as their relatives for lip pits, especially when there is a family history of mixed clefting, in order to make the VWS diagnosis. Dentists may also play an important role in diagnosing cases not detected at birth, as they detect hypodontia commonly associated with VWS. The

patients most commonly lack the upper second premolars followed by the lower second premolars and upper lateral incisors. The absence of these teeth might play a role in the constricting of the dental arches.

The clinical signs seen in VWS are similar to those of popliteal pterygium syndrome (PPS), which is also an autosomal dominant disease. Approximately 46% of affected individuals have lip pits; other features include genital abnormalities, abnormal skin near nails, syndactyly of fingers and toes, and webbed skin. The disease is also caused by mutations in "IRF6"; however, they occur in the DNA-binding domain of "IRF6" and result in a dominant negative effect in which the mutated IRF6 transcription factor interferes with the ability of the wild type copy to function, in the case of a heterozygous individual.

Symptoms are related to defects in connective tissue.

- Congenital anterior dislocation of the knees

- Dislocation of hips and shoulders

- Flattened facial appearance

- Prominent forehead

- Depressed nasal bridge

- Club foot

- Cervical kyphosis

Cardiac defects are similar to those associated with Marfan's syndrome, a disorder of the connective tissue.

- Elongation of aorta

- Bicuspid aortic valve

- Subaortic stenosis

- Mitral valve prolapse with mitral regurgitation

- Atrial septal defect

- Patent ductus arteriosus

- Tricuspid valve prolapse

- Aortic dissection and aneurysm

- Aneurysm of ductus arteriosus

The most prominent symptoms of BPES are horizontally narrow eyes (blepharophimosis), drooping eyelids (ptosis), and a fold of skin running from the side of the nose to the lower eyelid (epicanthus inversus). Other common symptoms include lack of an eyelid fold, widely spaced eyes (telecanthus), low nose bridge, and ear malformations (including cupping and incomplete development). Rare symptoms include microphthalmos (abnormally small eyes), tear ducts in the wrong location, and high arched palate. Female infertility can occur with type I BPES.

The cranium consists of three main sections including the base of the cranium (occipital bone), the face (frontal bone), and the top (parietal bones) and sides (temporal bone) of the head. Most of the bones of the cranium are permanently set into place prior to birth. However, the temporal and parietal bones are separated by sutures, which remain open, allowing the head to slightly change in shape during childbirth. The cranial sutures eventually close within the first couple of years following birth, after the brain has finished growing.

In individuals with SCS, the coronal suture separating the frontal bones from the parietal bones, closes prematurely (craniosynostosis), occasionally even before birth. If the coronal suture closes asymmetrically or unilaterally, then the face and forehead will form unevenly, from side-to-side. People with SCS have pointy, tower-like heads because their brain is growing faster than their skull, resulting in increased intracranial pressure (ICP) and causing the top of the head and/or forehead to bulge out to allow for brain growth. The face appears uneven, particularly in the areas of the eyes and cheeks, and the forehead appears wide and tall.

Because of the abnormal forehead, there is less space for the normal facial features to develop. This results in shallow eye sockets and flat cheekbones. The shallow eye sockets make the eyes more prominent or bulging and cause the eyes to be more separated than normal (hypertelorism). The underdeveloped eye sockets, cheekbones, and lower jaw cause the face to appear flat. Furthermore, the minor downward slant of the eyes along with the drooping eyelids (ptosis) adds to the overall unevenness of the face.

Individuals with SCS are all affected differently. Even within the same family, affected individuals have different features. The majority of individuals with SCS are moderately affected, with uneven facial features and a relatively flat face due to underdeveloped eye sockets, cheekbones, and lower jaw. In addition to the physical abnormalities, people with SCS also experience growth delays, which results in a relatively short stature. Although, most individuals with SCS are of normal intelligence, some individuals may have mild to moderate mental retardation (IQ from 50-70). More severe cases of SCS, with more serious facial deformities, occurs when multiple cranial sutures close prematurely.

Signs and symptoms are related to type and severity of the heart defect. Symptoms frequently present early in life, but it is possible for some CHDs to go undetected throughout life. Some children have no signs while others may exhibit shortness of breath, cyanosis, fainting, heart murmur, under-development of limbs and muscles, poor feeding or growth, or respiratory infections. Congenital heart defects cause abnormal heart structure resulting in production of certain sounds called heart murmur. These can sometimes be detected by auscultation; however, not all heart murmurs are caused by congenital heart defects.

3C syndrome, also known as CCC dysplasia, Craniocerebellocardiac dysplasia or Ritscher–Schinzel syndrome, is a rare condition, whose symptoms include heart defects, cerebellar hypoplasia, and cranial dysmorphism. It was first described in the medical literature in 1987 by Ritscher and Schinzel, for whom the disorder is sometimes named.

Congenital heart defects are associated with an increased incidence of some other symptoms, together being called the VACTERL association:

- V — Vertebral anomalies

- A — Anal atresia

- C — Cardiovascular anomalies

- T — Tracheoesophageal fistula

- E — Esophageal atresia

- R — Renal (Kidney) and/or radial anomalies

- L — Limb defects

Ventricular septal defect (VSD), atrial septal defects, and tetralogy of Fallot are the most common congenital heart defects seen in the VACTERL association. Less common defects in the association are truncus arteriosus and transposition of the great arteries.

Blepharophimosis, ptosis, epicanthus inversus syndrome or BPES is a rare disease characterized by the conditions it is named after: blepharophimosis, ptosis, and epicanthus inversus.

Malpuech syndrome is congenital, being apparent at birth. It is characterized by a feature known as facial clefting. Observed and noted in the initial description of the syndrome as a cleft lip and palate, facial clefting is identified by clefts in the bones, muscles and tissues of the face, including the lips and palate. The forms of cleft lip and palate typically seen with Malpuech syndrome are midline (down the middle of the lip and palate) or bilateral (affecting both sides of the mouth and palate). Facial clefting generally encompasses a wide range of severity, ranging from minor anomalies such as a (split) uvula, to a cleft lip and palate, to major developmental and structural defects of the facial bones and soft tissues. Clefting of the lip and palate occurs during embryogenesis. Additional facial and ortho-dental anomalies that have been described with the syndrome include: hypertelorism (unusually wide-set eyes, sometimes reported as telecanthus), narrow palpebral fissures (the separation between the upper and lower eyelids) and ptosis (drooping) of the eyelids, frontal bossing (prominent eyebrow ridge) with synophris, highly arched eyebrows, wide nasal root and a flattened nasal tip, malar hypoplasia (underdeveloped upper cheek bone), micrognathia (an undersized lower jaw), and prominent incisors. Auditory anomalies include an enlarged ear ridge, and hearing impairment associated with congenital otitis media (or "glue ear", inflammation of the middle ear) and sensorineural hearing loss.

Another feature identified with Malpuech syndrome is a caudal appendage. A caudal appendage is a congenital outgrowth stemming from the coccyx (tailbone). Present in many non-human animal species as a typical tail, this feature when seen in an infant has been described as a "human tail". This was observed by Guion-Almeida (1995) in three individuals from Brazil. The appendage on X-rays variously appeared as a prominent protrusion of the coccyx. On a physical examination, the appendage resembles a nodule-like stub of an animal tail.

Deficiencies such as mental retardation, learning disability, growth retardation and developmental delay are common. Psychiatric manifestations that have been reported with the syndrome include psychotic behavior, obsessive–compulsive disorder, loss of inhibition, hyperactivity, aggression, fear of physical contact, and compulsive actions like echolalia (repeating the words spoken by another person). Neuromuscular tics have also been noted.

Urogenital abnormalities, or those affecting the urinary and reproductive systems, are common with the syndrome. Malpuech et al. (1983) and Kerstjens-Frederikse et al. (2005) reported variously in affected males a micropenis, hypospadias (a congenital mislocation of the urinary meatus), cryptorchidism ( or undescended testes), bifid (split) and underdeveloped scrotum, and an obstructive urethral valve. An affected boy was also reported by Reardon et al. (2001) with left renal agenesis, an enlarged and downwardly displaced right kidney, cryptorchidism and a shawl scrotum. Other malformations that have been noted with the syndrome are omphalocele and an umbilical hernia.

Congenital abnormalities of the heart have also been observed with Malpuech syndrome. From a healthy Japanese couple, Chinen and Naritomi (1995) described the sixth child who had features consistent with the disorder. This two-month-old male infant was also affected by cardiac anomalies including patent ductus arteriosus (PDA) and ventricular septal defect. The opening in the ductus arteriosus associated with PDA had been surgically repaired in the infant at 38 days of age. A number of minor skeletal aberrations were also reported in the infant, including wormian bones at the lambdoid sutures.

Most of the signs of MWS are present during the neonatal period. The most common signs at this state are multiple congenital joint contractures, dysmorphic features with mask-like face, blepharophimosis, ptosis, micrognathia, cleft or high arched palate, low-set ears, arachnodactyly, chest deformation as pectus, kyphoscoliosis and absent deep tendon reflexes are frequent minor malformations have also been described and consist of renal anomalies, cardiovascular abnormalities, hypospadias, omphalomesenteric duct, hypertriphic pyloric stenosis, duodenal bands, hyoplastic right lower lobe of the lung, displacement of the larynx to the right and vertebral abnormalities, cerebral malformations.

- 75% of children with MWS have blepharophimosis, small mouth, micrognathia, kyphosis/scoliosis, radio ulnar synostose and multiple contractures.

- They have severe developmental delay; congenital joint contractures and blepharophimosis should be present in every patient

- 2 out of 3 of the following signs should be manifested: post natal growth, mask-like faces, retardation, and decreased muscular mass.

- Some may require additional signs such as; micrognathia, high arched or cleft palate, low set ears, kyphoscoliosis.

- The symptoms of MWS are normally diagnosed during the newborn period

Michels syndrome is a syndrome characterised by intellectual disability, craniosynostosis, blepharophimosis, ptosis, epicanthus inversus, highly arched eyebrows, and hypertelorism. And vary in other symptoms such as asymmetry of the skull, eyelid, and anterior chamber anomalies, cleft lip and palate, umbilical anomalies, and growth and cognitive development.

Van der Woude syndrome (VDWS) is a genetic disorder characterized by the combination of lower lip pits, cleft lip with or without cleft palate, and cleft palate alone (CP). The frequency of orofacial clefts ranges from 1:1000 to 1:500 births worldwide, and there are more than 400 syndromes that involve cleft lip with or without cleft palate. VWS is distinct from other clefting syndromes due to the combination of cleft lip and palate (CLP) and CP within the same family. Other features frequently associated with VWS include hypodontia in 10-81% of cases, narrow arched palate, congenital heart disease, heart murmur and cerebral abnormalities, syndactyly of the hands, polythelia, ankyloglossia, and adhesions between the upper and lower gum pads.

The association between lower lip pits and cleft lip and/or palate was first described by Anne Van der Woude in 1954. The worldwide disease incidence ranges from 1:100,000 to 1:40,000.

These are pleomorphic and include

- dolichocephaly (with or without sagittal suture synostosis)

- microcephaly

- pre- and postnatal growth retardation

- brachydactyly

- narrow thorax

- rhizomelic dwarfism

- epicanthal folds

- hypodontia and/or microdontia

- sparse, slow-growing, hyperpigmented, fine hair

- nail dysplasia

- hypohydrosis

- chronic renal failure

- heart defects

- liver fibrosis

- visual deficits

- photophobia

- hypoplasia of the posterior corpus callosum

- aberrant calcium homeostasis

Electroretinography shows gross abnormalities.

Two fetuses of 19 and 23 weeks gestation have also been reported. They showed acromesomelic shortening, craniofacial characteristics with absence of craniosynostosis, small kidneys with tubular and glomerular microscopic cysts, persistent ductal plate with portal fibrosis in the liver, small adrenals, an enlarged cisterna magna and a posterior fossa cyst.

The natural history of MWS is not well known: many patients died in infancy and clinical follow-up has been reported in few surviving adults. However, diagnosis may be more difficult to establish in adults patients, such as: blepharophimosis, contractures, growth retardation, and developmental delay, whereas minor face anomalies are less noticeable as the patient grows older. Throughout the development of the patient from young child to older adult changes the behavior drastically, from kindness to restless and hyperactive to aggressive.

In dentistry, anodontia, also called anodontia vera, is a rare genetic disorder characterized by the congenital absence of all primary or permanent teeth. It is associated with the group of skin and nerve syndromes called the ectodermal dysplasias. Anodontia is usually part of a syndrome and seldom occurs as an isolated entity.

Congenital absence of permanent teeth can present as hypodontia, usually missing 1 or 2 permanent teeth, or oligodontia that is the congenital absence of 6 or more teeth. Congenital absence of all wisdom teeth, or third molars, is relatively common. Anodontia is the congenital absence of teeth and can occur in some or all teeth (partial anodontia or hypodontia), involve two dentitions or only teeth of the permanent dentition (Dorland's 1998). Approximately 1% of the population suffers from oligodontia. Many denominations are attributed to this anomaly: partial anodontia, hypodontia, oligodontia, the congenital absence, anodontia, bilateral aplasia. Anodontia being the term used in controlled vocabulary Medical Subject Headings (MeSH) from MEDLINE which was developed by the United States National Library of Medicine. The congenital absence of at least one permanent tooth is the most common dental anomaly and may contribute to masticator dysfunction, speech impairment, aesthetic problems, and malocclusion (Shapiro and Farrington 1983). Absence of lateral incisors represents a major stereotype. Individuals with this condition are perceived as socially most aggressive compared with people without anodontia (Shaw 1981).

Zadik–Barak–Levin syndrome (ZBLS) is a congenital disorder in humans. Presenting conditions include primary hypothyroidism, cleft palate, hypodontia, and ectodermal dysplasia. It is the result of an embryonic defect in the mesodermal-ectodermal midline development.

Microlissencephaly with mildly to moderately thick (6–8 mm) cortex, callosal agenesis

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.

Malpuech facial clefting syndrome, also called Malpuech syndrome or Gypsy type facial clefting syndrome, is a rare congenital syndrome. It is characterized by facial clefting (any type of cleft in the bones and tissues of the face, including a cleft lip and palate), a appendage (a "human tail"), growth deficiency, intellectual and developmental disability, and abnormalities of the renal system (kidneys) and the male genitalia. Abnormalities of the heart, and other skeletal malformations may also be present. The syndrome was initially described by Guilliaume Malpuech and associates in 1983. It is thought to be genetically related to Juberg-Hayward syndrome. Malpuech syndrome has also been considered as part of a spectrum of congenital genetic disorders associated with similar facial, urogenital and skeletal anomalies. Termed "3MC syndrome", this proposed spectrum includes Malpuech, Michels and Mingarelli-Carnevale (OSA) syndromes. Mutations in the "COLLEC11" and "MASP1" genes are believed to be a cause of these syndromes. The incidence of Malpuech syndrome is unknown. The pattern of inheritance is autosomal recessive, which means a defective (mutated) gene associated with the syndrome is located on an autosome, and the syndrome occurs when two copies of this defective gene are inherited.

Numerous associated abnormalities of other organ systems may be present. This heterogeneity requires comprehensive evaluation of all patients and treatment regimes that can vary from modification of activities to extensive spinal surgeries. Furthermore, it is unclear whether Klippel–Feil syndrome is a unique disease, or if it is one part of a spectrum of congenital spinal deformities. Klippel–Feil syndrome is usually diagnosed after birth.

The most common sign of the disorder is restricted mobility of the neck and upper spine. A short neck and low hairline at the back of the head may occur in some patients.

Associated abnormalities may include:

- scoliosis (side-to-side curvature of the spine), which is abnormal curving of the spine. The spine sometimes appears as a "C" or an "S"

- spina bifida, when the spinal canal and the back bone do not close completely during birth

- anomalies of the kidneys and the ribs

- cleft palate (hole in the roof of the mouth)

- dental problems (late dentition, high-risk of caries, oligo- and hypodontia)

- respiratory problems

- heart malformations

- short stature

- Duane syndrome

- Approximately 35% of patients with Klippel–Feil syndrome will also have a congenital elevation of the scapula known as Sprengel's deformity

The disorder also may be associated with abnormalities of the head and face, skeleton, sex organs, muscles, brain and spinal cord, arms, legs, fingers and heart defects. These heart defects often lead to a shortened life expectancy, the average being 35–45 years of age among males and 40–50 among females. This condition is similar to the heart failure seen in gigantism.

In 2011, a study identifying the occurrence of symptoms of 100 patients was published.