It involves numerous anomalies including:

- Post-axial polydactyly

- Congenital heart defects (most commonly an atrial septal defect producing a common atrium, occurring in 60% of affected individuals)

- Teeth present at birth (natal teeth)

- Fingernail dysplasia

- Short-limbed dwarfism, mesomelic pattern

- Short ribs

- Cleft palate

- Malformation of the wrist bones (fusion of the hamate and capitate bones).

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).

Clinically, McKusick–Kaufman syndrome is characterized by a combination of three features: postaxial polydactyly, heart defects, and genital abnormalities:

- Vaginal atresia with hydrometrocolpos

- Double vagina and/or uterus.

- Hypospadias, chordee (a downward-curving penis), and undescended testes (cryptorchidism).

- ureter stenosis or ureteric atresia

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

EEM syndrome exhibits a combination of prominent symptoms and features. These include: ectodermal dysplasia (systemic malformations of ectodermal tissues), ectrodactyly ("lobster claw" deformity in the hands and feet), macular dystrophy (a progressive eye disease), syndactyly (webbed fingers or toes), hypotrichosis (a type of hair-loss), and dental abnormalities (hypodontia).

People with the combination of Duane anomaly and radial ray malformations may have a variety of other signs and symptoms. These features include:

- Unusually shaped ears

- Hearing loss

- Heart and kidney defects

- A distinctive facial appearance

- An inward- and downward-turning foot (a clubfoot)

- Fused vertebrae.

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

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.

This is characterized by hand and arm abnormalities. The following are specific characteristics:

- Malformed or absent (aplasia) thumb

- A thumb that looks more like a finger

- Partial or complete absence of a radius

- Shortening and radial deviation of the forearms

- Triphalangeal thumb

- Duplication of the thumb (preaxial polydactyly)

Pfeiffer syndrome is a very rare genetic disorder characterized by the premature fusion of certain bones of the skull which affects the shape of the head and face. In addition, the syndrome includes abnormalities of the hands (such as wide and deviated thumbs) and feet (such as wide and deviated big toes). Pfeiffer syndrome affects about 1 in 100,000 births.

Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder. In many cases, these growths do not cause any medical problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister–Hall syndrome include a malformation of the airway called a bifid epiglottis, laryngeal cleft, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications.

Majewski's polydactyly syndrome, also known as polydactyly with neonatal chondrodystrophy type I, short rib-polydactyly syndrome type II, and short rib-polydactyly syndrome, is a lethal form of neonatal dwarfism characterized by osteochondrodysplasia (skeletal abnormalities in the development of bone and cartilage) with a narrow thorax, polysyndactyly, disproportionately short tibiae, thorax dysplasia, hypoplastic lungs and respiratory insufficiency. Associated anomalies include protruding abdomen, brachydactyly, peculiar faces, hypoplastic epiglottis, cardiovascular defects, renal cysts, and also genital anomalies. Death occurs before or at birth.

The disease is inherited in an autosomal recessive pattern.

It was characterized in 1971.

McKusick–Kaufman syndrome is a genetic condition associated with MKKS.

The condition is named for Dr. Robert L. Kaufman and Victor McKusick. It is sometimes known by the abbreviation MKS. In infancy it can be difficult to distinguish between MKS and the related Bardet–Biedl syndrome, as the more severe symptoms of the latter condition rarely materialise before adulthood.

Sugarman syndrome is the common name of autosomal recessive oral-facial-digital syndrome type III, one of ten distinct genetic disorders that involve developmental defects to the mouth.

Alternative names for this condition include: Brachydactyly of the hands and feet with duplication of the first toes, Sugarman brachydactyly and Brachydactyly with major proximal phalangeal shortening.

Impossible Syndrome, or Chondrodysplasia situs inversus imperforate anus polydactyly, is a complex combination of human congenital malformations (birth defects).

The malformations include chondrodysplasia (improper growth of bone and cartilage), situs inversus totalis (chest and abdominal organs all a mirror image of normal), cleft larynx and epiglottis, hexadactyly (six digits) on hands and feet, diaphragmatic hernia, pancreatic abnormalities, kidney abnormal on one side and absent on the other side, micropenis and ambiguous genitalia, and imperforate anus.

Only one case of Impossible Syndrome has been reported; the infant was premature and stillborn.

All people with this disorder have at least one limb abnormality that affects bones in the wrist (carpal bones). Often, these wrist bone abnormalities can be detected only by X-ray. Affected individuals may have additional bone abnormalities that can include polydactyly, a hypoplastic thumb or a Triphalangeal thumb, partial or complete absence of bones in the forearm, an underdeveloped Humerus, and abnormalities that affect the Clavicle and Scapula. Bone abnormalities may affect each arm differently, and the left side can be affected more than the right side. In some cases, only one arm and/or hand is affected.

About 75 percent of individuals with Holt–Oram syndrome have heart problems. The most common problem is a defect in the muscular wall, or septum, that separates the right and left sides of the heart (atria). Atrial septal defects (ASD) are caused by a hole in the septum between the left and right upper chambers of the heart (atria), and ventricular septal defects (VSD) are caused by a hole in the septum between the left and right lower chambers of the heart (ventricles). Sometimes people with Holt–Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slow heart rate (bradycardia) or a rapid and ineffective contraction of the heart muscles (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as septal defects) or as the only heart problem in people with Holt–Oram syndrome.

As noted above, the hypothalamic hamartoma can cause seizures.

The most common types of seizures that occur are known as gelastic epilepsy.

The term "gelastic" originates from the Greek word ""gelos" which means "laughter". Seizures may begin at any age but usually before three or four years of age. The seizures usually start with laughter and the laughter is often described as being "hollow" or "empty" and not very pleasant. The laughter occurs suddenly, comes on for no obvious reason and is usually completely out of place. The most common areas of the brain which give rise to gelastic seizures are the hypothalamus (a small but extremely important structure deep in the centre of the brain), the temporal lobes and the frontal lobes. If the child has gelastic seizures and precocious puberty, then it is likely that the child will be found to have a hypothalamic hamartoma (a hamartoma in the hypothalamus part of the brain).

Symptoms vary from case to case, and may correlate to how much of the chromosome is missing. Symptoms that are frequently observed with the condition include:

- Low birth weight

- Malformations of the head

- Eye abnormalities

- Defects of the hands and feet, polydactyly

- Reproductive abnormalities (males)

- Psychological and motor retardation

Common relevant features of acrocephalosyndactyly are a high-arched palate, pseudomandibular prognathism (appearing as mandibular prognathism), a narrow palate, and crowding of the teeth.

Young–Madders syndrome is detectable from the fetal stage of development largely due to the distinctive consequences of holoprosencephaly, a spectrum of defects or malformations of the brain and face. Facial defects which may manifest in the eyes, nose, and upper lip, featuring cyclopia, anosmia, or in the growth of only a single central incisor, and severe overlapping of the bones of the skull. Cardiac and in some cases pulmonary deformities are present. Another signature deformity is bilateral polydactyly, and many patients also suffer from hypoplasia and genital deformities.

Aphalangy, hemivertebrae and urogenital-intestinal dysgenesis is an extremely rare syndrome, described only in three siblings. It associates hypoplasia or aplasia of phalanges of hands and feet, hemivertebrae and various urogenital and/or intestinal abnormalities. Intrafamilial variability is important as one sister had lethal abnormalities (Potter sequence and pulmonary hypoplasia), while her affected brother was in good health with normal psychomotor development at 6 months of age. Prognosis seems to depend mainly on the severity of visceral malformations. Etiology and inheritance remain unknown.

Ellis–van Creveld Syndrome (also called "chondroectodermal dysplasia" or "mesoectodermal dysplasia" but see 'Nomenclature' section below) is a rare genetic disorder of the skeletal dysplasia type.

Beare–Stevenson cutis gyrata syndrome is a rare genetic disorder characterized by craniosynostosis (premature fusion of certain bones of the skull, sometimes resulting in a characteristic 'cloverleaf skull'; further growth of the skull is prevented, and therefore the shape of the head and face is abnormal) and a specific skin abnormality, called cutis gyrata, characterized by a furrowed and wrinkled appearance (particularly in the face and on the palms and soles of the feet); thick, dark, velvety areas of skin (acanthosis nigricans) are sometimes found on the hands and feet and in the groin.

Additional signs and symptoms of Beare–Stevenson cutis gyrata syndrome can include a blockage of the nasal passages (choanal atresia), overgrowth of the umbilical stump, and abnormalities of the genitalia and anus. The medical complications associated with this condition are often severe and may well be life-threatening in infancy or early childhood.

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.

Acrocallosal syndrome (also known as ACLS) is a rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and mental retardation, and other symptoms. The syndrome was first described by Albert Schinzel in 1979.

It is associated with "GLI3".