Genetic counseling for VWS involves discussion of disease transmission in the autosomal dominant manner and possibilities for penetrance and expression in offspring. Autosomal dominance means affected parents have a 50% chance of passing on their mutated "IRF6" allele to a their child. Furthermore, if a cleft patient has lip pits, he or she has a ten times greater risk of having a child with cleft lip with or without cleft palate than a cleft patient who does not have lip pits. Types of clefting between parents and affected children are significantly associated; however, different types of clefts may occur horizontally and vertically within the same pedigree. In cases where clefting is the only symptom, a complete family history must be taken to ensure the patient does not have non-syndromic clefting.

Lip pits may be surgically removed either for aesthetic reasons or discomfort due to inflammation caused by bacterial infections or chronic saliva excretion, though spontaneous shrinkage of the lip pits has occurred in some rare cases. Chronic inflammation has also been reported to cause squamous-cell carcinoma. It is essential to completely remove the entire lip pit canal, as mucoid cysts can develop if mucous glands are not removed. A possible side effect of removing the lip pits is a loose lip muscle. Other conditions associated with VWS, including CL, CP, congenital heart defects, etc. are surgically corrected or otherwise treated as they would be if they were non-syndromic.

Usually observed at birth or shortly thereafter in 94% of patients, in other reports, patients did not develop skin lesions until 3 months or even 2 years after birth. Females are typically affected more often than males (64%).

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 prognosis is favorable in most patients with an isolated cutaneous abnormality. In the majority of cases, both the vivid red marking and the difference in circumference of the extremities regress spontaneously during the first year of life. It is theorized that this may be due to the normal maturation process, with thickening of the epidermis and dermis. Improvements for some patients can continue for up to 10 years, while in other cases, the marbled skin may persist for the patient's lifetime.

One study reported an improvement in lesions in 46% of patients within 3 years. If CMTC persists into adulthood, it can result in complaints due to paresthesia, increased sensitivity to cold and pain, and the formation of ulcers.

Few reports included long-term follow up of CMTC into adolescence and adulthood. While about 50% of patients seem to show definite improvement in the reticular vascular pattern, the exact incidence and cause of persistent cases are unknown.

The cause of fibular hemimelia is unclear. Purportedly, there have been some incidents of genetic distribution in a family; however, this does not account for all cases. Maternal viral infections, embryonic trauma, teratogenic environmental exposures or vascular dysgenesis (failure of the embryo to form a satisfactory blood supply) between four and seven weeks gestation are considered possible causes.

In an experimental mouse model, change in the expression of a homeobox gene led to similar, but bilateral, fibular defects.

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.

Although many perinatal and prenatal risk factors for ONH have been suggested, the predominant, enduring, most frequent risk factors are young maternal age and primiparity (the affected child being the first child born to the mother). Increased frequency of delivery by caesarean section and fetal/neonatal complications, preterm labor, gestational vaginal bleeding, low maternal weight gain, and weight loss during pregnancy are also associated with ONH.

The condition arises from some factor or set of factors present during approximately the 3rd week to 7th week of fetal development. Formation of the sacrum/lower back and corresponding nervous system is usually nearing completion by the 4th week of development. Due to abnormal gastrulation, the mesoderm migration is disturbed. This disturbance results in symptoms varying from minor lesions of the lower vertebrae to more severe symptoms such as complete fusion of the lower limbs. While the exact cause is unknown, it has been speculated that the condition may be associated with certain dietary deficiencies including a lack or insufficient amounts of folic acid.

Sacral agenesis syndrome (agenesis of the lumbar spine, sacrum, and coccyx, and hypoplasia of the lower extremities) is a well-established congenital anomaly associated with maternal diabetes mellitus (not gestational diabetes). However, other causes are presumably involved, as demonstrated by the rare incidence of caudal regression syndrome (1:60,000) compared to diabetes.

The dominant inherited sacral agenesis (also referred to as Currarino syndrome) is very often correlated with a mutation in the Hb9 (also called HlxB9) gene (shown by Sally Ann Lynch, 1995, Nature Genetics).

It may be the cause of sirenomelia ("Mermaid syndrome").

Caudal regression syndrome or sacral agenesis (or hypoplasia of the sacrum) is a congenital disorder in which there is abnormal fetal development of the lower spine—the caudal partition of the spine.

It occurs at a rate of approximately one per 25,000 live births.

Mutations of genes involved in transcription regulation, chromatin remodelling, α-dystroglycan glycosylation, cytoskeleton and scaffolding protein, RNA splicing, and the MAP kinase signalling pathway are currently known to cause ONH. Many transcription factors for eye development are also involved in the morphogenesis of forebrain, which may explain why ONH is commonly a part of a syndrome involving brain malformations.

ONH impacts all ethnic groups, although in the United States, occurrence is lower in persons of Asian descent. To date, there have been few reports of ONH occurrence in Asian countries, although it is uncertain why this is so.

Fibular hemimelia or longitudinal fibular deficiency is "the congenital absence of the fibula and it is the most common congenital absence of long bone of the extremities." It is the shortening of the fibula at birth, or the complete lack thereof. In humans, the disorder can be noted by ultrasound in utero to prepare for amputation after birth or complex bone lengthening surgery. The amputation usually takes place at six months with removal of portions of the legs to prepare them for prosthetic use. The other treatments which include repeated corrective osteotomies and leg-lengthening surgery (Ilizarov apparatus) are costly and associated with residual deformity.

Asymmetric crying facies (ACF), also called Cayler cardiofacial syndrome, partial unilateral facial paresis and hypoplasia of depressor angula oris muscle, is a minor congenital anomaly caused by agenesis or hypoplasia of the depressor anguli oris muscle, one of the muscles that control the movements of the lower lip. This unilateral facial weakness is first noticed when the infant cries or smiles, affecting only one corner of the mouth and occurs on the left side in nearly 80% of cases. It is associated with other birth defects in more than 50% of cases.

When the hypoplasia of the depressor anguli oris muscle is associated with congenital cardiac defects, the term 'Cayler cardiofacial syndrome' is used.

Cayler syndrome is part of 22q11.2 deletion syndrome.

It was characterized by Cayler in 1969.

Aural atresia is the underdevelopment of the middle ear and canal and usually occurs in conjunction with microtia. Atresia occurs because patients with microtia may not have an external opening to the ear canal, though. However, the cochlea and other inner ear structures are usually present. The grade of microtia usually correlates to the degree of development of the middle ear.

Microtia is usually isolated, but may occur in conjunction with hemifacial microsomia, Goldenhar Syndrome or Treacher-Collins Syndrome. It is also occasionally associated with kidney abnormalities (rarely life-threatening), and jaw problems, and more rarely, heart defects and vertebral deformities.

Microtia is a congenital deformity where the pinna (external ear) is underdeveloped. A completely undeveloped pinna is referred to as anotia. Because microtia and anotia have the same origin, it can be referred to as microtia-anotia. Microtia can be unilateral (one side only) or bilateral (affecting both sides). Microtia occurs in 1 out of about 8,000–10,000 births. In unilateral microtia, the right ear is most commonly affected. It may occur as a complication of taking Accutane (isotretinoin) during pregnancy.

Weismann-Netter-Stuhl syndrome, also known as Weismann-Netter Syndrome or more technically by the term tibioperoneal diaphyseal toxopachyosteosis, is a rare disorder characterized by bowing of the lower legs and an abnormal thickening of thinner bone in the leg.

The main sign is anterior bowing and posterior cortical thickening of the diaphyses of both the tibiae and fibulae. It is thought to be inherited in an autosomal dominant fashion, and is most often bilateral and symmetric in nature. Associated features include dwarfism and mild intellectual disability, as well as a process known as tibialization of the fibulae, which involves thickening and enlargement of these bones to an extent resembling the tibiae. The combination of the presence of tibialization of the fibulae, which is highly specific for the disorder, and the absence of laboratory abnormalities ruling out alternative diagnoses including rickets, essentially confirms the diagnosis.

Wearing shoes to protect barefoot trauma has shown decrease in incidence in ainhum. Congenital pseudoainhum cannot be prevented and can lead to serious birth defects.

Blount's disease occurs in young children and adolescents. The cause is unknown but is thought to be due to the effects of weight on the growth plate. The inner part of the tibia, just below the knee, fails to develop normally, causing angulation of the bone.

Unlike bowlegs, which tend to straighten as the child develops, Blount's disease is progressive and the condition worsens. It can cause severe bowing of the legs and can affect one or both legs.

This condition is more common among children of African ancestry. It is also associated with obesity, short stature, and early walking. There does not appear to be an obvious genetic factor.

Pathology is insertional tendinopathy of the medius and tendons and enlargement of the associated bursa.

Gluteals remain inactive in a seated position. Movements that require muscles become more difficult; stress is put on the spine.

The most extensive epidemiological survey on this congenital malformation has been carried out by Dharmasena et al and using English National Hospital Episode Statistics, they calculated the annual incidence of anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus from 1999 to 2011. According to this study the annual incidence of congenital microphthalmia in the United Kingdom was 10.8 (8.2 to 13.5) in 1999 and 10.0 (7.6 to 12.4) in 2011.

Spondyloepiphyseal dysplasia congenita (abbreviated to SED more often than SDC) is a rare disorder of bone growth that results in dwarfism, characteristic skeletal abnormalities, and occasionally problems with vision and hearing. The name of the condition indicates that it affects the bones of the spine (spondylo-) and the ends of bones (epiphyses), and that it is present from birth (congenital). The signs and symptoms of spondyloepiphyseal dysplasia congenita are similar to, but milder than, the related skeletal disorders achondrogenesis type 2 and hypochondrogenesis. Spondyloepiphyseal dysplasia congenita is a subtype of collagenopathy, types II and XI.

Individuals with CAVD can reproduce with the assistance of modern technology with a combination of testicular sperm extraction and intracytoplasmic sperm injection (ICSI). However, as the risk of either cystic fibrosis or renal agenesis is likely to be higher in the children, genetic counseling is generally recommended.

There are two main populations of CAVD; the larger group is associated with

cystic fibrosis and occurs because of a mutation in the CFTR gene, while the smaller group (estimated between 10 and 40%) is associated with Unilateral Renal agenesis (URA). The genetic basis of this second group is not well understood.

Mutation of the CFTR gene is found to result in obstructive azoospermia in postpubertal males with cystic fibrosis. Strikingly, CAVD is one of the most consistent features of cystic fibrosis as it affects 98-99% of individuals in this CF patient population. In contrast, acute or persistent respiratory symptoms present in only 51% of total CF patients.

In the subset of males with both CBAVD and URA, the CFTR mutation has been shown to occur at a rate only slightly higher than the overall population. Thus, McCallum, et al. have suggested another mutation may be responsible for this condition.

The cause of PFFD is uncertain. Two hypotheses have been advanced. The theory of sclerotome subtraction posits injury to neural crest cells that are the precursors to sensory nerves at the level of L4 and L5. Histologic studies of a fetus with unilateral PFFD have prompted an alternative hypothesis that PFFD is caused by a defect in maturation of chondrocytes (cartilage cells) at the growth plate. In either hypothesis, the agent causing the injury is usually not known. Thalidomide is known to cause PFFD when the mother is exposed to it in the fifth or sixth week of pregnancy, and it is speculated that exposure to other toxins during pregnancy may also be a cause. Other etiologies that have been suggested, but not proven, include anoxia, ischemia, radiation, infection, hormones, and mechanical force. PFFD occurs sporadically, and does not appear to be hereditary.

The most prominent and extensively documented findings of Weismann-Netter-Stuhl syndrome are on plain radiographs of the bones. Findings include bilateral and symmetric anterior bowing of both tibiae and fibulae, lateral bowing of the tibiae, femoral bowing, and squaring of iliac and pelvis bones.