Malformations of the upper extremities can occur In the third to seventh embryonic week. In some cases the TPT is hereditary. In these cases, there is a mutation on chromosome 7q36. If the TPT is hereditary, it is mostly inherited as an autosomal dominant trait, non-opposable and bilateral. The sporadic cases are mostly opposable and unilateral.

Triphalangeal thumb can occur in syndromes but it can also be isolated. The triphalangeal thumb can appear in combination with other malformations or syndromes.

Syndromes include:

- Holt-Oram syndrome

- Aase syndrome

- Blackfan-Diamond syndrome

- Townes-Brocks syndrome

Malformations include:

- Radial polydactyly

- Syndactyly

- Claw-like hand or foot

Type VII of radial polydactyly is associated with several syndromes:

Holt–Oram syndrome, Fanconi anemia (aplastic anemia by the age of 6), Townes–Brocks syndrome, and Greig cephalopolysyndactyly (also known to occur with ulnar polydactyly).

Ectrodactyly can be caused by various changes to 7q. When 7q is altered by a deletion or a translocation ectrodactyly can sometimes be associated with hearing loss. Ectrodactyly, or Split hand/split foot malformation (SHFM) type 1 is the only form of split hand/ malformation associated with sensorineural hearing loss.

The syndromes associated with central polydactyly are:

Bardet–Biedl syndrome,

Meckel syndrome,

Pallister–Hall syndrome,

Legius syndrome,

Holt–Oram syndrome,

Also, central polydactyly can be associated with syndactyly and cleft hand.

Other syndromes including polydactyly include acrocallosal syndrome, basal cell nevus syndrome, Biemond syndrome, ectrodactyly-ectodermal dysplasias-cleft lip/palate syndrome, mirror hand deformity, Mohr syndrome, oral-facial-digital syndrome, Rubinstein-Taybi syndrome, short rib polydactyly, and VATER association.

It can also occur with a triphalangeal thumb.

A large number of human gene defects can cause ectrodactyly. The most common mode of inheritance is autosomal dominant with reduced penetrance, while autosomal recessive and X-linked forms occur more rarely. Ectrodactyly can also be caused by a duplication on 10q24. Detailed studies of a number of mouse models for ectrodactyly have also revealed that a failure to maintain median apical ectodermal ridge (AER) signalling can be the main pathogenic mechanism in triggering this abnormality.

A number of factors make the identification of the genetic defects underlying human ectrodactyly a complicated process: the limited number of families linked to each split hand/foot malformation (SHFM) locus, the large number of morphogens involved in limb development, the complex interactions between these morphogens, the involvement of modifier genes, and the presumed involvement of multiple gene or long-range regulatory elements in some cases of ectrodactyly. In the clinical setting these genetic characteristics can become problematic and making predictions of carrier status and severity of the disease impossible to predict.

In 2011, a novel mutation in DLX5 was found to be involved in SHFM.

Ectrodactyly is frequently seen with other congenital anomalies. Syndromes in which ectrodactyly is associated with other abnormalities can occur when two or more genes are affected by a chromosomal rearrangement. Disorders associated with ectrodactyly include Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) syndrome, which is closely correlated to the ADULT syndrome and Limb-mammary (LMS) syndrome, Ectrodactyly-Cleft Palate (ECP) syndrome, Ectrodactyly-Ectodermal Dysplasia-Macular Dystrophy syndrome, Ectrodactyly-Fibular Aplasia/Hypoplasia (EFA) syndrome, and Ectrodactyly-Polydactyly. More than 50 syndromes and associations involving ectrodactyly are distinguished in the London Dysmorphology Database.

Omphalocele has been described in two patients with Apert syndrome by Herman T.E. et al. (USA, 2010) and by Ercoli G. et al. (Argentina, 2014). An omphalocele is a birth defect in which an intestine or other abdominal organs are outside of the body of an infant because of a hole in the bellybutton area. However, the association between omphalocele and Apert syndrome is not confirmed yet, so additional studies are necessary.

Surgery is needed to prevent the closing of the coronal sutures from damaging brain development. In particular, surgeries for the LeFort III or monobloc midface distraction osteogenesis which detaches the midface or the entire upper face, respectively, from the rest of the skull, are performed in order to reposition them in the correct plane. These surgeries are performed by both plastic and oral and maxillofacial (OMS) surgeons, often in collaboration.

Synpolydactyly is a joint presentation of syndactyly (fusion of digits) and polydactyly (production of supernumerary digits). This is often a result of a mutation in the HOX D13 gene.

Types include:

Hand-foot-genital syndrome is inherited in an autosomal dominant manner. The proportion of cases caused by de novo mutations is unknown because of the small number of individuals described. If a parent of the proband is affected, the risk to the siblings is 50%. When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low. Each child of an individual with HFGS has a 50% chance of inheriting the mutation. Prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing mutation has been identified in an affected family member.

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).

When it comes to treatment it is important to differentiate a thumb that needs stability, more web width and function, or a thumb that needs to be replaced by the index finger. Severe thumb hypoplasia is best treated by pollicization of the index finger. Less severe thumb hypoplasia can be reconstructed by first web space release, ligament reconstruction and muscle or tendon transfer.

It has been recommended that pollicization is performed before 12 months, but a long-term study of pollicizations performed between the age of 9 months and 16 years showed no differences in function related to age at operation.

It is important to know that every reconstruction of the thumb never gives a normal thumb, because there is always a decline of function. When a child has a good index finger, wrist and fore-arm the maximum strength of the thumb will be 50% after surgery in comparison with a normal thumb. The less developed the index finger, wrist and fore-arm is, the less strength the reconstructed thumb will have after surgery.

Not much research has been done on the epidemiology of congenital trigger thumbs. There are a few reports on the incidence in their respective studies. The most recent data comes from a Japanese study by Kukichi and Ogino where they found an incidence 3.3 trigger thumbs per 1,000 live births in 1 year old children.

Diagnosis is based on physical examination including radiographs of the hands and feet and imaging studies of the kidneys, bladder, and female reproductive tract. HOXA13 is the only gene known to be associated with HFGS. Approximately 60% of mutations are polyalanine expansions. Molecular genetic testing is clinically available.

The inheritance of Impossible syndrome is suspected to be autosomal recessive, which means the affected gene is located on an autosome, and two copies of the gene - one from each parent - are required to have an infant with the disorder.

Oligodactyly (from the Ancient Greek "oligos" meaning "few" and δάκτυλος "daktylos" meaning "finger") is the presence of fewer than five fingers or toes on a hand or foot.

It is quite often incorrectly called "hypodactyly", but the Greek prefixes and are used for scales (e.g. in hypoglycaemia and hypercholesterolemia). This as opposed to or scales, where and should be used (e.g. in oligarchy and polygamy). Oligodactyly is therefore the opposite of polydactyly. Very rare, this medical condition usually has a genetic or familial cause.

Oligodactyly is sometimes a sign or symptom of several syndromes including Poland syndrome and Weyer Ulnar Ray Syndrome. It is a type of Dysmelia.

Ectrodactyly is an extreme instance of oligodactyly, involving the absence of one or more central digits of the hand or foot and is also known as split hand/split foot malformation (SHFM). The hands and feet of people with ectrodactyly are often described as "claw-like" and may include only the thumb and one finger (usually either the little finger, ring finger, or a syndactyly of the two) with similar abnormalities of the feet.

People with oligodactyly often have full use of the remaining digits and adapt well to their condition. They are not greatly hindered in their daily activities, if at all. Even those with the most extreme forms are known to engage in tasks that require fine control, such as writing and bootmaking as well as working as a cab driver.

Vadoma people of Zimbabwe have a high frequency of oligodactyly.

Patients with abnormal cardiac and kidney function may be more at risk for hemolytic uremic syndrome

Polysyndactyly is an hereditary anatomical malformation combining polydactyly and syndactyly. There is also a type called "crossed" polysyndactyly

"Infant’s persistent thumb-clutched hand, flexion-adduction deformity of the thumb, pollex varus, thumb in the hand deformity."

Congenital clasped thumb describes an anomaly which is characterized by a fixed thumb into the palm at the metacarpophalangeal joint in one or both hands.

The incidence and genetic background are unknown. A study of Weckesser et al. showed that boys are twice as often affected with congenital clasped thumb compared to girls. The anomaly is in most cases bilateral (present in both hands).

A congenital clasped thumb can be an isolated anomaly, but can also be attributed to several syndromes.

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

The incidence of VACTERL association is estimated to be approximately 1 in 10,000 to 1 in 40,000 live-born infants. It is seen more frequently in infants born to diabetic mothers. While most cases are sporadic, there are clearly families who present with multiple involved members.

Dysmelia can be caused by

- inheritance of abnormal genes, e.g. polydactyly, ectrodactyly or brachydactyly, symptoms of deformed limbs then often occur in combination with other symptoms (syndromes)

- external causes during pregnancy (thus not inherited), e.g. via amniotic band syndrome

- teratogenic drugs (e.g. thalidomide, which causes phocomelia) or environmental chemicals

- ionizing radiation (nuclear weapons, radioiodine, radiation therapy)

- infections

- metabolic imbalance

Three main support groups of this syndrome are the ASGA in Australia, The Association for Children with Genetic Disorders in Poland, and the Association of People of Genetic Disorders in Greece.

The Wassel classification is used to categorise radial polydactyly, based upon the most proximal level of skeletal duplication.

A high-arched palate (also termed high-vaulted palate) is where the palate is unusually high and narrow. It is usually a developmental feature that may occur in isolation or in association with a number of conditions. It may also be an acquired condition caused by chronic thumb-sucking. High-arched palate may cause narrowed airway and sleep disordered breathing.

Example conditions which may be associated with high-arched palate include:

- Crouzon syndrome

- Down syndrome

- Apert syndrome

- Treacher Collins syndrome

- Marfan syndrome

- Incontinentia pigmenti