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.

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.

Features of YVS include growth retardation before and after birth, defective growth of the bones of the skull along with complete or partial absence of the shoulder blades and characteristic facial features. Additional symptoms may include abnormalities of the fingers and/or toes. In most cases, infants with this disorder experience severe feeding problems and respiratory difficulties. In addition, affected infants may have heart defects.

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.

Clinical expressions of PPS are highly variable, but include the following:

- Limb findings: an extensive web running from behind the knee down to the heel (90%), malformed toenails, and webbed toes.

- Facial findings: cleft palate with or without cleft lip (75%), pits in the lower lip (40%), and fibrous bands in the mouth known as syngnathia (25%).

- Genital findings (50%): hypoplasia of the labia majora, malformation of the scrotum, and cryptorchidism.

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

This is a very rare situation, in which the extra digit is on the ring, middle or index finger. Of these fingers, the index finger is most often affected, whereas the ring finger is rarely affected.

This type of polydactyly can be associated with syndactyly, cleft hand and several syndromes.

Polysyndactyly presents various degrees of syndactyly affecting fingers three and four.

Classification is performed by using x-ray imaging to see the bone structures.

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).

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.

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.

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).

Diagnosing the congenital clasped thumb is difficult in the first three to four months of life, as it is normal when the thumb is clutched into the palm in these first months.

Diagnoses that cause the same flexion or adduction abnormalities of the thumb are:

- Congenital clasped thumb

- Congenital Trigger thumb (flexion of the interphalangeal joint) - Trigger finger

- Spasticity: overstimulation of muscles

Syndrome associated flexion-adduction of the thumb:

- Freeman-Sheldon syndrome (a congenital, heritable affection of the face, the hands, the feet and some joints)

- Distal arthrogryposis

- MASA syndrome

- X-linked hydrocephalus

- Adducted thumb syndrome

- Waardenburg syndrome

- Whistling face syndrome (Freeman-Sheldon syndrome)

- Digitotalar dysmorphism

- Multiple pterygium syndrome

Hand-foot-genital syndrome (HFGS) is characterized by limb malformations and urogenital defects. Mild bilateral shortening of the thumbs and great toes, caused primarily by shortening of the distal phalanx and/or the first metacarpal or metatarsal, is the most common limb malformation and results in impaired dexterity or apposition of the thumbs. Urogenital abnormalities include abnormalities of the ureters and urethra and various degrees of incomplete Müllerian fusion in females and hypospadias of variable severity with or without chordee in males. Vesicoureteral reflux, recurrent urinary tract infections, and chronic pyelonephritis are common; fertility is normal.

The symptoms of phocomelia syndrome are undeveloped limbs and absent pelvic bones; however, various abnormalities can occur to the limbs and bones. Usually the upper limbs are not fully formed and sections of the "hands and arms may be missing." Short arm bones, fused fingers, and missing thumbs will often occur. Legs and feet are also affected similarly to the arms and hands. Individuals with phocomelia will often lack thigh bones, and the hands or feet may be abnormally small or appear as stumps due to their close "attachment to the body."

According to NORD, individuals carrying phocomelia syndrome will generally show symptoms of growth retardation previous to and after birth. The syndrome can also cause severe mental deficiencies in infants. Infants born with phocomelia will normally have a petite head with "sparse hair" that may appear "silvery-blonde." Hemangioma, the abnormal buildup of blood vessels, will possibly develop around the facial area at birth and the eyes may be set widely apart, a condition known as orbital hypertelorism. The pigment of the eyes will be a bluish white. Phocomelia can also cause: an undeveloped nose with slender nostrils, disfigured ears, irregularly petite jaws [also known as micrognathia], and a cleft lip with cleft palate. According to NORD, severe symptoms of phocomelia include:

- A fissure of the skull and a projecting brain known as (encephalocele)

- An accumulation of spinal fluid under the skull also known as hydrocephalus; causing vomiting and migraines

- An abnormally shaped uterus (bicornuate)

- Inability to clot blood efficiently due to a low amount of platelets running through the blood

- Malformations in the kidney and heart

- Shortened neck

- Abnormalities in the urethra

Generally, triphalangeal thumbs are non-opposable. In contrast to most people with opposable thumbs, a person suffering from TPT cannot easily place his or her thumb opposite the other four digits of the same hand. The opposable thumb's ability to effortlessly utilize fingers in a "pinch" formation is critical in precision gripping. For the thumb to adequately grip, certain thumb criteria must be met (e.g. suitable position and length, stable joints and good thenar muscle strength). Because triphalangeal thumbs cannot easily oppose and do not possess many of the optimal qualities found in most opposable thumbs, they tend to cause the hand to be less effective in use and, therefore, prove to be more problematic in daily life.

TBS patients may have the following symptoms:

- Abnormalities of the external ears (unusually large or small, unusually shaped, sometimes with sensorineural hearing loss or deafness due to lesions or dysfunctions of part of the internal ear or its nerve tracts and centers or conductive hearing loss from the external or middle ear), dysplastic ears, lop ear (over-folded ear helix), preauricular tags or pits (a rudimentary tag of ear tissue typically located just in front of the ear).

- Anorectal malformations, including imperforate anus/absence of an anal opening, rectovaginal fistula, anal stenosis, unusually placed anus.

- Renal abnormalities, sometimes leading to impaired renal function or renal failure, including hypoplastic kidneys (underdeveloped), multicystic kidneys, dyspastic kidneys.

- Heart abnormalities, including tetralogy of fallot and defects of the ventricular septum.

- Hand and foot abnormalities, such as hypoplastic thumbs, fingerlike thumbs, syndactyly (webbed fingers/toes), fusion of the wrist bones, overlapping foot and/or toe bones.

Learning difficulties have been reported in some children with TBS. For others, intelligence is within the normal range.

These abnormalities, which are present prenatally, can range from minor to severe, and as with similar disorders, most individuals with this condition have some, but not all, of these traits.

Popliteal pterygium syndrome (PPS) is an inherited condition affecting the face, limbs, and genitalia. The syndrome goes by a number of names including the "popliteal web syndrome" and, more inclusively, the "facio-genito-popliteal syndrome". The term PPS was coined by Gorlin "et al.." in 1968 on the basis of the most unusual anomaly, the popliteal pterygium (a web behind the knee).

Yunis–Varon syndrome (YVS), also called cleidocranial dysplasia with micrognathia, absent thumbs and distal aphalangia, is an extremely rare autosomal recessive multisystem congenital disorder which affects the skeletal system, ectodermal tissue, heart and respiratory system.

Additional findings that may be present in HFGS according to the latest research are:

- Limited metacarpophalangeal flexion of the thumb or limited ability to oppose the thumb and fifth finger

- Hypoplastic thenar eminences

- Medial deviation of the great toe (hallux varus), a useful diagnostic sign when present

- Small great toenail

- Fifth-finger clinodactyly, secondary to a shortened middle phalanx

- Short feet

- Altered dermatoglyphics of the hands; when present, primarily involving distal placement of the axial triradius, lack of thenar or hypothenar patterning, low arches on the thumbs, thin ulnar loops (deficiency of radial loops and whorls), and a greatly reduced ridge count on the fingers

Radiographic findings

- Hypoplasia of the distal phalanx and first metacarpal of the thumbs and great toes

- Pointed distal phalanges of the thumb

- Lack of normal tufting of the distal phalanges of the great toes

- Fusions of the cuneiform to other tarsal bones or trapezium-scaphoid fusion of the carpals

- Short calcaneus

- Occasional bony fusions of the middle and distal phalanges of the second, third, fourth, or fifth toes

- Delayed carpal or tarsal maturation

- Metacarpophalangeal profile reflecting shortening of the first metacarpal, the first and second phalanges, and the second phalanx of the second and fifth digits

Urogenital Defects

Females may have the following:

- Vesicoureteral reflux secondary to ureteric incompetence

- Ectopic ureteral orifices

- Trigonal hypoplasia

- Hypospadiac urethra

- Subsymphyseal epispadias

- Patulous urethra

- Urinary incontinence (related to structural anomalies and weakness of the bladder sphincter muscle)

- Small hymenal opening

- Various degrees of incomplete Müllerian fusion with or without two cervices or a longitudinal vaginal septum

Males may have the following:

- Retrograde ejaculation (related to structural anomalies and weakness of the bladder sphincter muscle)

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

Arachnodactyly ("spider fingers") or achromachia is a condition in which the fingers and toes are abnormally long and slender, in comparison to the palm of the hand and arch of the foot. Also, the individual's thumbs tend to also be pulled inwards towards the palm. It can be present at birth or develop in later life.

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.

Not all of the DOOR symptoms are consistently present. They can vary in severity, and additional features can be noted in individuals affected by DOOR syndrome.

Some of these additional features are:

- Polyhydramnios (increased amniotic fluid during pregnancy) and increased nuchal fold during pregnancy

- Specific facial features such as a large nose

- Severe and sometimes refractory seizures, abnormalities on the magnetic resonance imaging of the brain

- Increased 2-oxoglutaric acid in the blood and urine - this compound is made or used by several enzymes

- Finger-like thumbs

- Visual impairment

- Peripheral neuropathy (nerves conducting sensation from extremities to the brain) and insensivity to pain

Intellectual impairment is present in all reported cases, but the severity can vary widely. The prognosis in terms of survival also varies greatly from early childhood till adulthood.

This feature can occur on its own, with no underlying health problems. However, it can also be associated with certain medical conditions. Examples include Marfan syndrome, Ehlers-Danlos syndrome, Loeys–Dietz syndrome, congenital contractural arachnodactyly, and homocystinuria.

Arachnodactyly has been linked to mutations in both fibrillin-1 and fibrillin-2 genes.