PHACE syndrome needs to be managed by a multidisciplinary team of experts. Additional specialties such as cardiology, ophthalmology, neurology, and neurosurgery may need to be involved. The team of experts pay close attention to how these children develop throughout the school age period.

PHACE Syndrome Handbook - Dr. Beth Drolet

In 2013, the PHACE Syndrome Community was formed. The non-profit entity was developed to raise awareness about the condition, support patients and families of those with the condition and raise money for research into causes and treatment.

Usually the hemangioma requires medical therapy. The child may need other therapies, depending on what other organs or structures are involved.

Management of AOS is largely symptomatic and aimed at treating the various congenital anomalies present in the individual. When the scalp and/or cranial bone defects are severe, early surgical intervention with grafting is indicated.

The overall prognosis is excellent in most cases. Most children with Adams–Oliver syndrome can likely expect to have a normal life span. However, individuals with more severe scalp and cranial defects may experience complications such as hemorrhage and meningitis, leading to long-term disability.

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

Probably, the most well-known teratogenic drug is thalidomide. It was developed near the end of the 1950s by Chemie Grűnenthal as a sleep inducing aid and antiemetic. Because of its ability to prevent nausea it was prescribed for pregnant women in almost 50 countries worldwide between 1956–1962. Until William McBride published the study leading to its withdrawal from the market at 1961, about 8- 10 000 severely malformed children were born. The most typical disorder induced by thalidomide were reductional deformities of the long bones of the extremities. Phocomelia otherwise a rare deformity, which therefore helped to recognise the teratogenic effect of the new drug. Among other malformations caused by thalidomide were those of ears, eyes, brain, kidney, heart, digestive and respiratory tract. 40% of the prenatally affected children died soon after birth. As thalidomide is used today as a treatment for multiple myeloma and leprosy, several births of affected children were described in spite of the strictly required use of contraception among female patients treated by it.

Vitamin A, or retinol, is the sole vitamin which is embryotoxic even in a therapeutic dose, for example in multivitamins, because its metabolite, the retinoic acid, plays an important role as a signal molecule in the development of several tisues and organs. Its natural precursor, the β-carotene, is considered safe, whereas the consumption of animal liver can lead to malformation, as the liver stores lipophile vitamins, including retinol. Isotretinoin (13-cis-retinoic-acid; brand name Roaccutane), vitamine A analog, which is often used to treat severe acne, is such a strong teratogen that just a single dose taken by a pregnant woman (even transdermally) may result in serious birth defects. Because of this effect, most countries have systems in place to ensure that it is not given to pregnant women, and that the patient is aware of how important it is to prevent pregnancy during and at least one month after treatment. Medical guidelines also suggest that pregnant women should limit vitamin A intake to about 700 μg/day, as it has teratogenic potential when consumed in excess. Vitamine A and similar substances can induce spontaneous abortions, premature births, defects of eyes (microphthalmia), ears, thymus, face deformities, neurological (hydrocephalus, microcephalia) and cardiovascular defects, as well as mental retardation.

Tetracycline, an antibiotic, should never be prescribed to women in the reproductive age or children, because of its negative impact on bone mineralization and teeth mineralization. The "tetracycline teeth" have brown or grey colour as a result of a defective development of both the dentine and the enamel of teeth.

Several anticonvulsants are known to be highly teratogenic. Phenytoin, also known as diphenylhydantoin, along with carbamazepine is responsible for the fetal hydantoin syndrome, which may typically include broad nose base, cleft lip and/or palate, microcephalia, nails and fingers hypoplasia, intrauterine growth restriction and mental retardation. Trimethadione taken during pregnancy is responsible for the fetal trimethadione syndrome, characterized by craniofacial, cardiovascular, renal and spine malformations, along with a delay in mental and physical development. Valproate has anti-folate effects, leading to neural tube closure-related defects such as spina bifida. Lower IQ and autism have recently also been reported as a result of intrauterine valproate exposure.

Hormonal contraception is considered as harmless for the embryo. Peterka and Novotná do however state that syntethic progestines used to prevent miscarriage in the past frequently caused masculinization of the outer reproductive organs of female newborns due to their androgenic activity. Diethylstilbestrol is a synthetic estrogen used from the 1940s to 1971 when the prenatal exposition has been linked to the clear-cell adenocarcinoma of the vagina. Following studies showed elevated risks for other tumors and congenital malformations of the sex organs for both sexes.

All cytostatics are strong teratogens, abortion is usually recommended when pregnancy is found during or before chemotherapy. Aminopterin, a cytostatic drug with anti-folate effect, was used during the 1950s and 1960s to induce therapeutic abortions. In some cases the abortion didn´t happen, but the newborns suffered a fetal aminopterin syndrome consisting of growth retardation, craniosynostosis, hydrocephalus, facial dismorphities, mental retardation and/or leg defomities

No cure or treatment option for individuals with Hydrolethalus syndrome currently exist.

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.

For the survivors of the atomic bombing of Hiroshima and Nagasaki, who are known as the "Hibakusha", no statistically demonstrable increase of birth defects/congenital malformations was found among their later conceived children, or found in the later conceived children of cancer survivors who had previously received radiotherapy.

The surviving women of Hiroshima and Nagasaki who were able to conceive, though exposed to substantial amounts of radiation, later had children with no higher incidence of abnormalities/birth defects than in the Japanese population as a whole.

Relatively few studies have researched the effects of paternal radiation exposure on offspring. Following the Chernobyl disaster, it was assumed in the 1990s that the germ line of irradiated fathers suffered minisatellite mutations in the DNA, which was inherited by descendants. more recently however, the World Health Organization states, "children conceived before or after their father's exposure showed no statistically significant differences in mutation frequencies". This statistically insignificant increase was also seen by independent researchers analyzing the children of the liquidators. Animal studies have shown that incomparably "massive" doses of X-ray irradiation of male mice resulted in birth defects of the offspring.

In the 1980s, a relatively high prevalence of pediatric leukemia cases in children living near a nuclear processing plant in West Cumbria, UK, led researchers to investigate whether the cancer was a result of paternal radiation exposure. A significant association between paternal irradiation and offspring cancer was found, but further research areas close to other nuclear processing plants did not produce the same results. Later this was determined to be the Seascale cluster in which the leading hypothesis is the influx of foreign workers, who have a different rate of leukemia within their race than the British average, resulted in the observed cluster of 6 children more than expected around Cumbria.

Hydrolethalus syndrome (less commonly referred to as Salonen-Herva-Norio syndrome) is a rare genetic disorder that causes improper fetal development, resulting in birth defects and often stillbirth.

It is associated with HYLS1 mutations.

The treatment of pentalogy of Cantrell is directed toward the specific symptoms that are apparent in each individual. Surgical intervention for cardiac, diaphragmatic and other associated defects is necessary. Affected infants will require complex medical care and may require surgical intervention. In most cases, pentalogy of Cantrell is fatal without surgical intervention. However, in some cases, the defects are so severe that the individual dies regardless of the medical or surgical interventions received.

The specific treatment strategy will vary from one infant to another based upon various factors, including the size and type of abdominal wall defect, the specific cardiac anomalies that are present, and the particular type of ectopia cordis. Surgical procedures that may be required shortly after birth include repair of an omphalocele. At this time, physicians may also attempt to repair certain other defects including defects of the sternum, diaphragm and the pericardium.

In severe cases, some physicians advocate for a staged repair of the defects associated with pentalogy of Cantrell. The initial operation immediately after birth provides separation of the peritoneal and pericardial cavities, coverage of the midline defect and repair of the omphalocele. After appropriate growth of the thoracic cavity and lungs, the second stage consists of the repair of cardiac defects and return of the heart to the chest. Eventually, usually by age 2 or 3, reconstruction of the lower sternum or epigastrium may be necessary.

Other treatment of pentalogy of Cantrell is symptomatic and supportive.

Oculofaciocardiodental syndrome is a rare X linked genetic disorder.

In 1996, the United States Food and Drug Administration published regulations requiring the addition of folic acid to enriched breads, cereals, flour and other grain products. It is important to note that during the first four weeks of pregnancy (when most women do not even realize that they are pregnant), adequate folate intake is essential for proper operation of the neurulation process. Therefore, women who could become pregnant are advised to eat foods fortified with folic acid or take supplements in addition to eating folate-rich foods to reduce the risks of serious birth defects.

In Canada, mandatory fortification of selected foods with folic acid has been shown to reduce the incidence of neural tube defects by 46%.

Women who may become pregnant are advised to get 400 micrograms of folic acid daily. Women who have previously given birth to a child with a neural tube defect may benefit from a supplement containing 4.0 mg/5.0 mg in the UK mg daily, following advice provided by their doctor.

If there are no other defects, the prognosis after surgical repair of this condition is relatively good. However, 10% of those with more severe or additional abnormalities die from it. The organs themselves are fully functional; the difficulty lies in fitting them inside the abdomen. The condition is, in fact, a hernia requiring only replacement and strengthening of the passageway through which it occurred. After surgery, increased pressure in the stretched abdomen can compromise the function of the organs inside.

Abdominal wall defects can be treated surgically if there is no accompanying anomalies. The surgical procedure also called omphalocele repair/closure or gastroschisis repair/closure is not overcomplicated. The organs are normal but are misplaced.

However, if the abdominal cavity is too small or when the organs are too large or swollen to close the skin, it may be difficult to fit all the viscera into the small abdominal cavity. In such cases, the surgeon will place a covering pouch generally made of silastic, commonly called a "silo" (because it's shaped like an agricultural silo), over the abdominal organs on the outside of the infant. The silo serves to conserve heat and prevent infection. The silo is spring-loaded so that the device can be attached to the inside of the abdominal wall without sutures. The top of the silo is secured in a way that causes it to stand upright, so that the bowels are gradually coaxed into the abdominal cavity by gravity. This process can take up to a week, and final closure may be performed a few weeks later. More surgery may be required to repair the abdominal muscles at a later time.

For patients with vWD type 1 and vWD type 2A, desmopressin is available as different preparations, recommended for use in cases of minor trauma, or in preparation for dental or minor surgical procedures. Desmopressin stimulates the release of vWF from the Weibel-Palade bodies of endothelial cells, thereby increasing the levels of vWF (as well as coagulant factor VIII) three- to five-fold. Desmopressin is also available as a preparation for intranasal administration (Stimate) and as a preparation for intravenous administration. Recently, the FDA has approved the use of Baxalta’s Vonvendi. This is the first recombinant form of vWF. The effectiveness of this treatment is different than desmopressin because it only contains vWF, not vWF with the addition of FVIII. This treatment is only recommended for use by individuals who are 18 years of age or older.

Desmopressin is contraindicated in vWD type 2b because of the risk of aggravated thrombocytopenia and thrombotic complications. Desmopressin is probably not effective in vWD type 2M and is rarely effective in vWD type 2N. It is totally ineffective in vWD type 3.

For women with heavy menstrual bleeding, estrogen-containing oral contraceptive medications are effective in reducing the frequency and duration of the menstrual periods. Estrogen and progesterone compounds available for use in the correction of menorrhagia are ethinylestradiol and levonorgestrel (Levona, Nordette, Lutera, Trivora). Administration of ethinylestradiol diminishes the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, leading to stabilization of the endometrial surface of the uterus.

Desmopressin is a synthetic analog of the natural antidiuretic hormone vasopressin. Its overuse can lead to water retention and dilutional hyponatremia with consequent convulsion.

For patients with vWD scheduled for surgery and cases of vWD disease complicated by clinically significant hemorrhage, human-derived medium purity factor VIII concentrates, which also contain von Willebrand factors, are available for prophylaxis and treatment. Humate P, Alphanate, Wilate and Koate HP are commercially available for prophylaxis and treatment of vWD. Monoclonally purified factor VIII concentrates and recombinant factor VIII concentrates contain insignificant quantity of vWF, so are not clinically useful.

Development of alloantibodies occurs in 10-15% of patients receiving human-derived medium-purity factor VIII concentrates and the risk of allergic reactions including anaphylaxis must be considered when administering these preparations. Administration of the latter is also associated with increased risk of venous thromboembolic complications.

Blood transfusions are given as needed to correct anemia and hypotension secondary to hypovolemia. Infusion of platelet concentrates is recommended for correction of hemorrhage associated with platelet-type vWD.

The antifibrinolytic agents epsilon amino caproic acid and tranexamic acid are useful adjuncts in the management of vWD complicated by clinical hemorrhage. The use topical thrombin JMI and topical Tisseel VH are effective adjuncts for correction of hemorrhage from wounds.

Fetal hydantoin syndrome, also called fetal dilantin syndrome is a group of defects caused to the developing fetus by exposure to teratogenic effects of phenytoin or carbamazepine. Dilantin is the brand name of the drug phenytoin sodium in the United States, commonly used in the treatment of epilepsy.

It may also be called congenital hydantoin syndrome, Fetal Hydantoin Syndrome, Dilantin Embryopathy, or Phenytoin Embryopathy.

Association with EPHX1 has been suggested.

The vWF gene is located on the short arm "p" of chromosome 12 (12p13.2). It has 52 exons spanning 178kbp. Types 1 and 2 are inherited as autosomal dominant traits and type 3 is inherited as autosomal recessive. Occasionally, type 2 also inherits recessively. vWD occurs in approximately 1% of the population and affects men and women equally.

In terms of treatment/management, bleeding events can be controlled by platelet transfusion.

Most heterozygotes, with few exceptions, do not have a bleeding diathesis. BSS presents as a bleeding disorder due to the inability of platelets to bind and aggregate at sites of vascular endothelial injury. In the event of an individual with mucosal bleeding tranexamic acid can be given.

The affected individual may need to avoid contact sports and medications such as aspirin, which can increase the possibility of bleeding. A potential complication is the possibility of the individual producing antiplatelet antibodies

A deficiency of folate itself does not cause neural tube defects. The association seen between reduced neural tube defects and folic acid supplementation is due to a gene-environment interaction such as vulnerability caused by the C677T Methylenetetrahydrofolate reductase (MTHFR) variant. Supplementing folic acid during pregnancy reduces the prevalence of NTDs by not exposing this otherwise sub-clinical mutation to aggravating conditions. Other potential causes can include folate antimetabolites (such as methotrexate), mycotoxins in contaminated corn meal, arsenic, hyperthermia in early development, and radiation. Maternal obesity has also been found to be a risk factor for NTDs. Studies have shown that both maternal cigarette smoking and maternal exposure to secondhand smoke increased the risk for neural tube defects in offspring. A mechanism by which maternal exposure to cigarette smoke could increase NTD risk in offspring is suggested by several studies that show an association between cigarette smoking and elevations of homocysteine levels. Cigarette smoke during pregnancy, including secondhand exposure, can increase the risk of neural tube defects. All of the above may act by interference with some aspect of normal folic acid metabolism and folate linked methylation related cellular processes as there are multiple genes of this type associated with neural tube defects.

About one third of children whose mothers are taking this drug during pregnancy typically have intrauterine growth restriction with a small head and develop minor dysmorphic craniofacial features and limb defects including hypoplastic nails and distal phalanges (birth defects). A smaller population will have growth problems and developmental delay, or intellectual disability. Methemoglobinemia is a rarely seen side effect.

Heart defects and cleft lip may also be featured.

The occurrence of ectopia cordis is 8 per million births. It is typically classified according to location of the ectopic heart, which includes:

- Cervical

- Thoracic

- Thoracoabdominal

- Abdominal

Thoracic and thoraco-abdominal ectopia cordis constitute the vast majority of known cases.

Pentalogy of Cantrell (or thoraco-abdominal syndrome) is a rare syndrome that causes defects involving the diaphragm, abdominal wall, pericardium, heart and lower sternum.

Its prevalence is less than 1 in 1000000.

It was characterized in 1958.

A locus at Xq25-26 has been described.

This condition is caused by lesions in the BCOR gene located on the short arm of the X chromosome (Xp11.4). This protein encodes the BCL6 corepressor but little is currently known about its function. The inheritance is X-linked dominant.

A genetically related disorder is Lenz microphthalmia syndrome.

Pre-formed metal crowns (PMC), also known as stainless steel crowns, can be used to reduce the risk of marginal breakdown, coronal leakage and has a good longevity. The use of preformed metal crowns on MIH-affected molars can prevent further tooth loss, control hypersensitivity and aim to establish correct interproximal and occlusal contact. They are relatively inexpensive and require little preparation.

To prevent further tooth preparation and tissue loss, use of the Hall Technique should also be considered. There advantage is use during any stage of post-eruptive breakdown, but evidence of their efficacy is limited. Although the PMC has evidence to show that it is well accepted, a few of the children and their carers expressed their concerns about the metallic appearances of the restoration.