Symptoms in people with Treacher Collins syndrome vary. Some individuals are so mildly affected that they remain undiagnosed, while others have moderate to severe facial involvement and life-threatening airway compromise. Most of the features of TCS are symmetrical and are already recognizable at birth.

The most common symptom of Treacher Collins syndrome is underdevelopment of the lower jaw and underdevelopment of the zygomatic bone. This can be accompanied by the tongue being retracted. The small mandible can result in a poor occlusion of the teeth or in more severe cases, trouble breathing or swallowing. Underdevelopment of the zygomatic bone gives the cheeks a sunken appearance.

The external ear is sometimes small, rotated, malformed, or absent entirely in people with TCS. Symmetric, bilateral narrowing or absence of the external ear canals is also described. In most cases, the bones of the middle ear and the middle ear cavity are misshapen. Inner ear malformations are rarely described. As a result of these abnormalities, a majority of the individuals with TCS have conductive hearing loss.

Most affected people also experience eye problems, including colobomata (notches) in the lower eyelids, partial or complete absence of eyelashes on the lower lid, downward angled eyelids, drooping of upper and lower eyelids, and narrowing of the tear ducts. Vision loss can occur and is associated with strabismus, refractive errors, and anisometropia. It can also be caused by severely dry eyes, a consequence of lower eyelid abnormalities and frequent eye infections.

Although an abnormally shaped skull is not distinctive for Treacher Collins syndrome, brachycephaly with bitemporal narrowing is sometimes observed. Cleft palate is also common.

Dental anomalies are seen in 60% of affected people, including tooth agenesis (33%), discoloration (enamel opacities) (20%), malplacement of the maxillary first molars (13%), and wide spacing of the teeth. In some cases, dental anomalies in combination with mandible hypoplasia result in a malocclusion. This can lead to problems with food intake and the ability to close the mouth.

Less common features of TCS may add to an affected person's breathing problems, including sleep apnea. Choanal atresia or stenosis is a narrowing or absence of the choanae, the internal opening of the nasal passages. Underdevelopment of the pharynx, can also narrow the airway.

Features related to TCS that are seen less frequently include nasal deformities, high-arched palate, macrostomia, preauricular hair displacement, cleft palate, hypertelorism, notched upper eyelid, and congenital heart defects.

The general public may associate facial deformity with developmental delay and intellectual disability, but more than 95% of people affected with TCS have normal intelligence. The psychological and social problems associated with facial deformity can affect quality of life in people with TCS.

The following is a list of symptoms that have been associated with Roberts syndrome:

- Bilateral Symmetric Tetraphocomelia- a birth defect in which the hands and feet are attached to shortened arms and legs

- Prenatal Growth Retardation

- Hypomelia (Hypoplasia)- the incomplete development of a tissue or organ; less drastic than aplasia, which is no development at all

- Oligodactyly- fewer than normal number of fingers or toes

- Thumb Aplasia- the absence of a thumb

- Syndactyly- condition in which two or more fingers (or toes) are joined together; the joining can involve the bones or just the skin between the fingers

- Clinodactyly- curving of the fifth finger (little finger) towards the fourth finger (ring finger) due to the underdevelopment of the middle bone in the fifth finger

- Elbow/Knee Flexion Contractures- an inability to fully straighten the arm or leg

- Cleft Lip- the presence of one or two vertical fissures in the upper lip; can be on one side (unilateral) or on both sides (bilateral)

- Cleft Palate- opening in the roof of the mouth

- Premaxillary Protrusion- upper part of the mouth sticks out farther than the lower part of the mouth

- Micrognathia- small chin

- Microbrachycephaly- smaller than normal head size

- Malar Hypoplasia- underdevelopment of the cheek bones

- Downslanting Palpebral Fissures- the outer corners of the eyes point downwards

- Ocular Hypertelorism- unusually wide-set eyes

- Exophthalmos- a protruding eyeball

- Corneal Clouding- clouding of the front-most part of the eye

- Hypoplastic Nasal Alae- narrowing of the nostrils that can decrease the width of the nasal base

- Beaked Nose- a nose with a prominent bridge that gives it the appearance of being curved

- Ear Malformations

- Intellectual disability

- Encephalocele (only in severe cases)- rare defect of the neural tube characterized by sac-like protrusions of the brain

Mortality is high among those severely affected by Roberts syndrome; however, mildly affected individuals may survive to adulthood

TCS is often first suspected with characteristic symptoms observed during a physical exam. However, the clinical presentation of TCS can resemble other diseases, making diagnosis difficult. The OMENS classification was developed as a comprehensive and stage-based approach to differentiate the diseases. This acronym describes five distinct dysmorphic manifestations, namely orbital asymmetry, mandibular hypoplasia, auricular deformity, nerve development, and soft-tissue disease.

Orbital symmetry

- O0: normal orbital size, position

- O1: abnormal orbital size

- O2: abnormal orbital position

- O3: abnormal orbital size and position

Mandible

- M0: normal mandible

- M1: small mandible and glenoid fossa with short ramus

- M2: ramus short and abnormally shaped

1. 2A: glenoid fossa in anatomical acceptable position

2. 2B: Temperomandibular joint inferiorly (TMJ), medially, anteriorly displaced, with severely hypoplastic condyle

- M3: Complete absence of ramus, glenoid fossa, and TMJ

Ear

- E0: normal ear

- E1: Minor hypoplasia and cupping with all structures present

- E2: Absence of external auditory canal with variable hypoplasia of the auricle

- E3: Malposition of the lobule with absent auricle, lobular remnant usually inferior anteriorly displaced

Facial nerve

- N0: No facial nerve involvement

- N1: Upper facial nerve involvement (temporal or zygomatic branches)

- N2: Lower facial nerve involvement (buccal, mandibular or cervical)

- N3: All branches affected

Soft tissue

- S0: No soft tissue or muscle deficiency

- S1: Minimal tissue or muscle deficiency

- S2: Moderate tissue or muscle deficiency

- S3: Severe tissue or muscle deficiency

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.

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.

There is a range of signs and symptoms including cleft lip or palate, mental retardation and various forms of ectodermal dysplasia. Additional symptoms may include fused eyelids, absent nails, delayed bone growth and dry skin. It is believed that this syndrome follows an autosomal dominant pattern of inheritance with incomplete penetrance, and caused by a mutation affecting the TP63 gene. It has been suggested that this syndrome, AEC syndrome and Rapp–Hodgkin syndrome may be variations of the same disease.

The key affected features of this condition are described in its name.

Scalp: There are raised nodules over the posterior aspect of the scalp, covered by scarred non-hair bearing skin.

Ears: The shape of the pinnae is abnormal, with the superior edge of the pinna being turned over more than usual. The size of the tragus, antitragus and lobule may be small.

Nipples: The nipples are absent or rudimentary. The breasts may be small or virtually absent.

Other features of the condition include:

Dental abnormalities: missing or widely spaced teeth

Syndactyly: toes or fingers may be partially joined proximally

Renal abnormalities: renal hypoplasia, pyeloureteral duplication

Eye abnormalities: Cataract, coloboma of the iris and asymmetric pupils.

It is characterized by developmental defects including cryptophthalmos (where the eyelids fail to separate in each eye), and malformations in the genitals (such as micropenis, cryptorchidism or clitoromegaly). Congenital malformations of the nose, ears, larynx and renal system, as well as mental retardation, manifest occasionally. Syndactyly (fused fingers or toes) has also been noted.

There is no specific treatment or cure for individuals affected with this type of syndrome, though some of the abnormal physical features may be surgically correctable.

Little is known about the natural history of Roberts syndrome due to its wide clinical variability. The prognosis of the disease depends on the malformations, as the severity of the malformations correlates with survival. The cause of death for most fatalities of Roberts syndrome have not been reported; however, five deaths were reportedly due to infection.

The following are observations that have been made in individuals with cytogenetic findings of PCS/HR or ESCO2 mutations:

- The symptom of prenatal growth retardation is the most common finding and can be moderate to severe. Postnatal growth retardation can also be moderate to severe and correlates with the degree of severity of limb and craniofacial malformations.

- In limb malformations, the upper limbs are typically more severely affected than the lower limbs. There have been many cases of only upper limb malformation.

- In hand malformations, the thumb is most often affected, followed by the fifth finger (the little finger). In severe cases, the patient may only have three fingers and in rare cases only one.

- In craniofacial malformations, mildly affected individuals will have no abnormalities of the palate. The most severely affected will have a fronto-ethmoid-nasal-maxillary encephalocele.

- The severity of limb malformations and craniofacial malformations is correlated.

- Other abnormalities can occur in different parts of the body, including:

- Heart- atrial septal defects, ventricular septal defects, patent ductus arteriosus

- Kidneys- polycystic kidney, horseshoe kidney

- Male Genitals- enlarged penis, cryptorchidism

- Female Genitals- enlarged clitoris

- Hair- sparse, silvery-blonde scalp hair

- Cranial Nerve Paralysis, Moyamoya disease, Stroke, Intellectual disability

Symptoms vary from one type of the syndrome to another and from one patient to another, but they include:

- Very pale or brilliantly blue eyes, eyes of two different colors (complete heterochromia), or eyes with one iris having two different colors (sectoral heterochromia)

- A forelock of white hair ("poliosis"), or premature graying of the hair

- Appearance of wide-set eyes due to a prominent, broad nasal root ("dystopia canthorum")—particularly associated with Type I) also known as "telecanthus"

- Moderate to profound hearing loss (higher frequency associated with Type II);

- A low hairline and eyebrows that meet in the middle ("synophrys")

- Patches of white skin pigmentation, in some cases

- Abnormalities of the arms, associated with Type III

- neurologic manifestations, associated with Type IV

- Cleft lip, mostly associated with Type I

Waardenburg syndrome has also been associated with a variety of other congenital disorders, such as intestinal and spinal defects, elevation of the scapula and cleft lip and palate. Sometimes this is concurrent with Hirschsprung disease.

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.

Nager acrofacial dysostosis is a genetic congenital anomaly syndrome. Nager syndrome displays several or all of the following characteristics: underdevelopment of the cheek and jaw area, down-sloping of the opening of the eyes, lack or absence of the lower eyelashes, kidney or stomach reflux, hammer toes, shortened soft palate, lack of development of the internal and external ear, possible cleft palate, underdevelopment or absence of the thumb, hearing loss (see hearing loss with craniofacial syndromes) and shortened forearms, as well as poor movement in the elbow, and may be characterized by accessory tragi. Occasionally, affected individuals develop vertebral anomalies such as scoliosis. The inheritance pattern is said to be autosomal but there are arguments as to whether it is autosomal dominant or autosomal recessive. Most cases tend to be sporadic. Nager syndrome is also linked to five other similar syndromes: Miller syndrome, Treacher Collins, Pierre Robin, Genee-Wiedemann, and Franceschetti-Zwahlen-Klein.

Franceschetti–Klein syndrome (also known as "Mandibulofacial dysostosis") is a syndrome that includes palpebral antimongoloid fissures, hypoplasia of the facial bones, macrostomia, vaulted palate, malformations of both the external and internal ear, buccal-auricular fistula, abnormal development of the neck with stretching of the cheeks, accessory facial fissures, and skeletal deformities.

It is sometimes equated with Treacher Collins syndrome.

The syndrome is a rare clinical disorder.

- Physical

- Overgrowth

- Accelerated skeletal maturation

- Dysmorphic facial features

- Prominent eyes

- Bluish sclerae

- Coarse eyebrows

- Upturned nose

- Radiologic examination

- Accelerated osseous maturation

- Phalangeal abnormalities

- Tubular thinning of the long bones

- Skull abnormalities

- Mental

- Often associated with intellectual disability (of variable degree)

Scalp–ear–nipple syndrome (also known as "Finlay–Marks syndrome") is a condition associated with aplasia cutis congenita.

Of those fetuses that do survive to gestation and subsequent birth, common abnormalities may include:

- Nervous system

- Intellectual disability and motor disorder

- Microcephaly

- Holoprosencephaly (failure of the forebrain to divide properly).

- Structural eye defects, including microphthalmia, Peters' anomaly, cataract, iris or fundus (coloboma), retinal dysplasia or retinal detachment, sensory nystagmus, cortical visual loss, and optic nerve hypoplasia

- Meningomyelocele (a spinal defect)

- Musculoskeletal and cutaneous

- Polydactyly (extra digits)

- Cyclopia

- Proboscis

- Congenital trigger digits

- Low-set ears

- Prominent heel

- Deformed feet known as rocker-bottom feet

- Omphalocele (abdominal defect)

- Abnormal palm pattern

- Overlapping of fingers over thumb

- Cutis aplasia (missing portion of the skin/hair)

- Cleft palate

- Urogenital

- Abnormal genitalia

- Kidney defects

- Other

- Heart defects (ventricular septal defect) (Patent Ductus Arteriosus)

- Dextrocardia

- Single umbilical artery

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.

Nager syndrome is thought to be caused by haploinsufficiency of the spliceosomal factor SF3B4.

Fraser syndrome (also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome) is an autosomal recessive congenital disorder. Fraser syndrome is named for the geneticist George R. Fraser, who first described the syndrome in 1962.

Low-set ears are ears with depressed positioning of the pinna two or more standard deviations below the population average.

It can be associated with conditions such as:

- Down's syndrome

- Turner Syndrome

- Noonan syndrome

- Patau syndrome

- DiGeorge syndrome

- Cri du chat syndrome

- Edwards syndrome

- Fragile X syndrome

It is usually bilateral, but can be unilateral in Goldenhar syndrome.

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.

Since the original identification of Schimmelpenning syndrome, the number of findings has expanded to the point that the syndrome is associated with a considerable constellation of abnormalities. The abnormalities may occur in a variety of combinations, and need not include all three aspects of the classic triad of sebaceous nevus, seizures and mental retardation. In 1998, a literature review by van de Warrenburg et al. found:

- seizures in 67% of cases

- mental retardation in 61% of cases

- ophthalmological abnormalities in 59% of cases

- involvement of other organ systems in 61% of cases

- structural abnormality of cerebrum or cranium in 72% of cases

The major neurological abnormalities include mental retardation to varying extent, seizures, and hemiparesis. Seizures, when present, typically begin during the first year of life. The most common structural central nervous system abnormalities in Schimmelpenning syndrome are hemimegalencephaly and ipselateral gyral malformations.

The major ocular abnormalities are colobomas and choristomas.

Skeletal abnormalities may include dental irregularities, scoliosis, vitamin D-resistant rickets and hypophosphatemia. Cardiovascular abnormalities include ventricular septal defect and co-arctation of the aorta; urinary system issues include horseshoe kidney and duplicated urinary collection system.

There is an overlap in symptoms between 3C syndrome and Joubert syndrome. Joubert syndrome often manifests with similar cerebellar hypoplasia and its sequelae, including hyperpnea, ataxia, changes in eye movement, and cleft lip and palate. Occasionally, Joubert syndrome will include heart malformations. Brachmann-de Lange syndrome must also be differentiated from 3C syndrome. It presents with similar craniofacial and heart abnormalities and can include Dandy-Walker phenotype, making it difficult to distinguish. Dandy-Walker malformation is also occasionally seen in Ellis-van Creveld syndrome, which is characterized by heart defects and malformed alveolar ridge. Many disorders include the Dandy-Walker phenotype and thus it is not pathognomonic for 3C syndrome.

CHARGE syndrome can also be misdiagnosed. This is because both CHARGE syndrome and 3C syndrome share symptoms of ocular colobomas, cardiac defects, growth retardation, and minor facial abnormalities.

Coffin-Siris syndrome presents with fifth-finger deformities and congenital heart defects. It is distinguished from 3C syndrome by differences in facial dysmorphisms.

Waardenburg syndrome is a rare genetic disorder most often characterized by varying degrees of deafness, minor defects in structures arising from the neural crest, and pigmentation changes. It was first described in 1951. The syndrome was later found to have four types. For example, type II was identified in 1971, to describe cases where dystopia canthorum was not present. Some types are now split into subtypes, based upon the gene responsible for the condition.