Renal (kidney) defects are seen in approximately 50 percent of patients with VACTERL association. In addition, up to 35 percent of patients with VACTERL association have a single umbilical artery (there are usually two arteries and one vein) which is often associated with additional kidney or urologic problems. Renal abnormalities in VACTERL association can be severe, with incomplete formation of one or both kidneys or urologic abnormalities such as obstruction of outflow of urine from the kidneys or severe reflux (backflow) of urine into the kidneys from the bladder. These problems can cause kidney failure early in life and may require kidney transplant. Many of these problems can be corrected surgically before any damage can occur.

Esophageal atresia with tracheo-esophageal fistula (TE fistula) is seen in about 70 percent of patients with VACTERL association, although it can frequently occur as an isolated defect. Fifteen percent to 33 percent of patients with TE fistulas will also have congenital heart disease. However these babies usually have uncomplicated heart defects, like a ventricular septal defect, which may not require any surgery.

Hemangiomas associated with PHACE Syndrome are usually small or not visible at birth, but are easier to see during the first days to weeks of life. They can grow rapidly. Hemangiomas linked with PHACE Syndrome tend to cover a large area of the face, head or neck, either as one lesion or as many single lesions.

As it grows, the hemangioma can break down skin, distort facial features or get in the way of other vital functions, such as breathing, vision, and hearing. Other complications will depend on what other structures are involved. These could include developmental delay, seizures, headaches, and abnormal muscle tone if the brain is involved.

Imperforate anus is associated with an increased incidence of some other specific anomalies as well, 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

Other entities associated with an imperforate anus are trisomies 18 and 21, the cat-eye syndrome (partial trisomy or tetrasomy of a maternally derived number 22 chromosome), Baller-Gerold syndrome, Currarino syndrome, caudal regression syndrome, FG syndrome, Johanson-Blizzard syndrome, McKusick-Kaufman syndrome, Pallister-Hall syndrome, short rib-polydactyly syndrome type 1, Townes-Brocks syndrome, 13q deletion syndrome, urorectal septum malformation sequence, and the OEIS complex (omphalocele, exstrophy of the cloaca, imperforate anus, spinal defects).

There are several forms of imperforate anus and anorectal malformations. The new classification is in relation of the type of associated fistula.

The classical Wingspread classification was in low and high anomalies:

- A low lesion, in which the colon remains close to the skin. In this case, there may be a stenosis (narrowing) of the anus, or the anus may be missing altogether, with the rectum ending in a blind pouch.

- A high lesion, in which the colon is higher up in the pelvis and there is a fistula connecting the rectum and the bladder, urethra or the vagina.

- A persistent cloaca (from the term cloaca, an analogous orifice in reptiles and amphibians), in which the rectum, vagina and urinary tract are joined into a single channel.

Imperforate anus is usually present along with other birth defects—spinal problems, heart problems, tracheoesophageal fistula, esophageal atresia, renal anomalies, and limb anomalies are among the possibilities.

The several components or degrees of development range from an ear tag, preauricular appendage, preauricular tag, or accessory tragus, to supernumerary ears or polyotia. It is a relatively common congenital anomaly of the first branchial arch or second branchial arches. Other anomalies may be present concurrently, including cleft palate, cleft lip, or mandibular hypoplasia. There is a known association with Goldenhar syndrome (oculo-auriculo-vertebral syndrome) and with Wildervanck syndrome. There may also be an association with congenital cartilaginous rest of the neck.

The general presentation is of a skin-covered nodule, papule, or nodule of the skin surface, usually immediately anterior to the auricle. However, it may be anywhere within the periauricular tissues. Bilateral presentation can be seen.

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.

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.

CHARGE syndrome (formerly known as CHARGE association), is a rare syndrome caused by a genetic disorder. First described in 1979, the acronym "CHARGE" came into use for newborn children with the congenital features of coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness. These features are no longer used in making a diagnosis of CHARGE syndrome, but the name remains. About two thirds of cases are due to a CHD7 mutation. CHARGE syndrome occurs only in 0.1–1.2 per 10,000 live births; as of 2009 it was the leading cause of congenital deafblindness in the US.

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).

Although genetic testing positively identifies nearly two thirds of children with CHARGE syndrome, diagnosis is still largely clinical. The following signs were originally identified in children with this syndrome, but are no longer used in to make the diagnosis alone.

- C - Coloboma of the eye, central nervous system anomalies

- H - Heart defects

- A - Atresia of the choanae

- R - Retardation of growth and/or development

- G - Genital and/or urinary defects (Hypogonadism, undescended testicles, besides hypospadias.)

- E - Ear anomalies and/or deafness and abnormally bowl-shaped and concave ears, known as "lop ears".

Other birth defects may co-exist, particularly in the heart, but sometimes also in the anus, spinal column, or kidneys. This is known as VACTERL association because of the involvement of Vertebral column, Anorectal, Cardiac, Tracheal, Esophageal, Renal, and Limbs. It is associated with polyhydramnios in the third trimester.

This birth defect arises in the fourth fetal week, when the trachea and esophagus should begin to separate from each other.

It can be associated with disorders of the tracheoesophageal septum.

Townes–Brocks syndrome (TBS) is a rare genetic disease that has been described in approximately 200 cases in the published literature. It affects both males and females equally. The condition was first identified in 1972. by Philip L. Townes, MD, PhD, who was at the time a human geneticists and Professor of Pediatrics, and Eric Brocks, MD, who was at the time a medical student, both at the University of Rochester.

Sirenomelia, alternatively known as Mermaid syndrome, is a rare congenital deformity in which the legs are fused together, giving them the appearance of a mermaid's tail as the nickname suggests.

This condition is found in approximately one out of every 100,000 live births (about as rare as conjoined twins) and is usually fatal within a day or two of birth because of complications associated with abnormal kidney and urinary bladder development and function. More than half the cases of sirenomelia result in stillbirth and this condition is 100 times more likely to occur in identical twins than in single births or fraternal twins. It results from a failure of normal vascular supply from the lower aorta in utero. Maternal diabetes has been associated with caudal regression syndrome and sirenomelia, although a few sources question this association.

VACTERL-H is an expanded form of the VACTERL association that concludes that this diagnosis is a less severe form of sirenomelia. The disorder was formerly thought to be an extreme case of caudal regression syndrome; however, it was reclassified to be considered a separate condition.

Hypoglossia is a short, incompletely developed tongue. It can occur either as an isolated malformation or in association with other deformities, particularly limb defects in a syndrome known as "oromandibular limb hypogenesis syndrome".

Renal-hepatic-pancreatic dysplasia is an autosomal recessive congenital disorder characterized by pancreatic fibrosis, renal dysplasia and hepatic dysgenesis. It is usually fatal soon after birth.

An association with NPHP3 has been described.

It was characterized in 1959.

Radial aplasia is a congenital defect which affects the formation of the radius bone in the arm. The radius is the lateral bone which connects to the wrist via articulation with the carpal bones. A child born with this condition has either a short or absent radius bone in one or both of his or her arm(s). Radial aplasia also results in the thumb being either partly formed or completely absent from the hand. Radial aplasia is connected with the condition VACTERL association. The cause for radial aplasia in unknown, but it widely believed to occur within the first ten weeks of gestation.

Vertebral anomalies is associated with an increased incidence of some other specific anomalies as well, 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

Acropectoral syndrome is an autosomal dominant skeletal dysplasia syndrome affecting the hands, feet, sternum, and lumbosacral spine. A recently proposed candidate gene for preaxial polydactyly is LMBR1, encoding a novel transmembrane receptor, which may be an upstream regulator of SHH. The LMBR1 gene is on human chromosome 7q36.

Some individuals have preaxial polydactyly in the feet (unilateral in one, bilateral in 13), consisting of a small extra biphalangeal toe, in most cases with an associated rudimentary extra metatarsal, lying in a soft tissue web between the hallux and second toe. In some cases, this was accompanied by hypoplasia of the head of the first metatarsal and absence of both phalanges of the hallux.

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.

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.