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.

Dental features:

- small teeth in males

- pointed (screwdriver shaped or conical) incisors (sometimes called Hutchinson teeth)

- incisors with an irregulal incisal edge

- canines: enlarged and globular; may be dome or bud shaped with trilobed edge

- premolars and molars: small, round and globular; may have supernumary lobes (mulberry or lotus flower shape)

- widely separated teeth (diastemma)

- hypoplastic enamel

- dental agenesis

- presence of mesiodents (median incisor behind normal upper incisors)

- pulp chamber anomalies

Facial features:

- anteverted pinnae

- long face

- prominent nasal bridge and nose

- prognathism occasionally

Ophthalmic features:

- bilateral congenital nuclear opacities (100%)

- severe amblyopia

- nystagmus (93%)

- strabismus (43%)

- microcornea (96%)

- congenital glaucoma

- scleral staphylomas

- retinal cystoid degeneration

- microphthalmia

These lead to severe visual impairment in affected males.

Other:

- The fourth metacarpal may be shortened

30% of patients also have some degree of intellectual impairment: of these 80% are mildly to moderately affected: the other 20% may have developmental delays and behavior problems.

Carrier females display milder variable symptoms of disease. Ocular signs are present in 90% of heterozygous females. These are typically lens opacities often involving the posterior Y sutures. More rarely dental anomalies and the characteristic facial features may also occur.

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.

The following features are observed with VACTERL association:

- V - Vertebral anomalies

- A - Anorectal malformations

- C - Cardiovascular anomalies

- T - Tracheoesophageal fistula

- E - Esophageal atresia

- R - Renal (Kidney) and/or radial anomalies

- L - Limb defects

Although it was not conclusive whether VACTERL should be defined by at least two or three component defects, it is typically defined by the presence of at least three of the above congenital malformations.

Neonatal complications (apart from congenital anomalies) are common. In a paper published in 2010, 41 of 42 individuals had some type medical problem in the first days of life, the most common being feeding difficulties. Respiratory difficulty and jaundice are also relatively frequent.

Cardiac anomalies are the most common congenital malformation in individuals with tetrasomy 18p. However, there is no pathognomatic heart defect associated with the condition. Patent ductus arteriosus is the most common defect. Septal defects (ventricular septal defects and atrial septal defects) are also common, as are patent foramina ovalia. Other cardiac anomalies include mitral valve regurgitation, mitral valve prolapse, bicuspid pulmonary valve, hypoplastic transverse aortic arch, tricuspid valve regurgitation, right ventricular hypertrophy, and pulmonic stenosis.

In males, cryptorchidism is common. Abnormal genitalia in females is not a common feature. Renal abnormalities have been reported in a minority of patients. Horseshoe kidney and bladder diverticuli have been reported. Other abdominal malformations, including pyloric stenosis and hernias, have also been reported, though they are present in only a minority of patients.

Orthopedic anomalies also occur relatively frequently, with hip dysplasia being the most common orthopedic issue. Clubfoot and rocker bottom feet have also been reported.

Myelomeningocele is another known feature associated with tetrasomy 18p.

There are numerous types, differentiated by the extent of the defect. These types are:

- Type I: simple defects leading to communication between the ascending aorta and pulmonic trunk

- Type II: defects that extend to the origin of the right pulmonary artery

- Type III: anomalous origin of the right pulmonary artery from the ascending aorta

It is also classified as simple or complex. Simple defects are those that do not require surgical repair, occur with no other defects, or those that require minor stright-forward repair (ductus arteriosus, atrial septal defect). Complex defects are those that occur with other anatomical anomalies or require non-standard repair.

Aneuploidy is often fatal, but in this case there is "X-inactivation" where the effect of the additional gene dosage due to the presence of extra X chromosomes is greatly reduced.

Much like Down syndrome, the mental effects of 49,XXXXY syndrome vary. Impaired speech and behavioral problems are typical. Those with 49,XXXXY syndrome tend to exhibit infantile secondary sex characteristics with sterility in adulthood and have some skeletal anomalies. Skeletal anomalies include:

- Genu valgum

- Pes cavus

- Fifth finger clinodactyly

The effects also include:

- Cleft palate

- Club feet

- Respiratory conditions

- Short or/and broad neck

- Low birth weight

- Hyperextensible joints

- Short stature

- Narrow shoulders

- Coarse features in older age

- Hypertelorism

- Epicanthal folds

- Prognathism

- Gynecomastia (rare)

- Muscular hypotonia

- Hypoplastic genitalia

- Cryptorchidism

- Congenital heart defects

- A very round face in infancy

Aortopulmonary septal defect is a rare congenital heart disorder accounting for only 0.1-0.3% of congenital heart defects worldwide. It is characterized by a communication between the aortic and pulmonary arteries, with preservation of two normal semilunar valves. It is the result of an incomplete separation of the aorticopulmonary trunk that normally occurs in early fetal development with formation of the spiral septum. Aortopulmonary septal defects occur in isolation in about half of cases, the remainder are associated with more complex heart abnormalities.

Usually associated with diaphragmatic hernia,

pulmonary hypoplasia,

imperforate anus,

micropenis,

bilateral cryptorchidism,

cerebral ventricular dilation,

camptodactyly,

agenesis of sacrum,

low-set ear.

- Fryns et al. (1979) reported 2 stillborn sisters with a multiple congenital anomaly syndrome characterized by coarse facies with cloudy corneae, diaphragmatic defects, absence of lung lobulation, and distal limb deformities. A sporadic case was reported by Goddeeris et al. (1980). Fitch (1988) claimed that she and her colleagues were the first to describe this disorder. In 1978 they reported a single infant, born of second-cousin parents, who had absent left hemidiaphragm, hydrocephalus, arhinencephaly, and cardiovascular anomalies.

- Lubinsky et al. (1983) reported a brother and sister with Fryns syndrome who both died in the neonatal period. Facial anomalies included broad nasal bridge, microretrognathia, abnormal helices, and cleft palate. Other features included distal digital hypoplasia, lung hypoplasia, and urogenital abnormalities, including shawl scrotum, uterus bicornis, and renal cysts. They were discordant for diaphragmatic hernia, cleft lip, and Dandy–Walker anomaly.

- Meinecke and Fryns (1985) reported an affected child; consanguinity of the parents supported recessive inheritance. They noted that a diaphragmatic defect had been described in 4 of the 5 reported cases and lung hypoplasia in all. Young et al. (1986) reported a sixth case. The male infant survived for 12 days. These authors listed corneal clouding, camptodactyly with hypoplastic nails, and abnormalities of the diaphragm as cardinal features.

- Samueloff et al. (1987) described a family in which all 4 children had Fryns syndrome and neonatal mortality. Features included hypoplastic lungs, cleft palate, retrognathia, micrognathism, small thorax, diaphragmatic hernia, distal limb hypoplasia, and early onset of polyhydramnios with premature delivery. Schwyzer et al. (1987) described an affected infant whose parents were second cousins.

- Moerman et al. (1988) described infant brother and sister with the syndrome of diaphragmatic hernia, abnormal face, and distal limb anomalies. Both died shortly after birth with severe respiratory distress. Ultrasonography demonstrated fetal hydrops, diaphragmatic hernia, and striking dilatation of the cerebral ventricles in both infants. Post-mortem examination showed Dandy–Walker malformation, ventricular septal defect, and renal cystic dysplasia.

- Cunniff et al. (1990) described affected brothers and 3 other cases, bringing the total reported cases of Fryns syndrome to 25. One of the affected brothers was still alive at the age of 24 months. Bilateral diaphragmatic hernias had been repaired on the first day of life. He required extracorporeal membrane oxygenation therapy for 5 days and oscillatory therapy for 3 months. Ventriculoperitoneal shunt was required because of slowly progressive hydrocephalus. Scoliosis was associated with extranumerary vertebral bodies and 13 ribs. Because of delayed gastric emptying, a gastrostomy tube was inserted. In addition, because of persistent chylothorax, he underwent decortication of the right lung and oversewing of the thoracic duct.

- Kershisnik et al. (1991) suggested that osteochondrodysplasia is a feature of Fryns syndrome.

- Willems et al. (1991) suggested that a diaphragmatic hernia is not a necessary feature of Fryns syndrome. They described a child with all the usual features except for diaphragmatic hernia; the diaphragm was reduced to a fibrous web with little muscular component. Bartsch et al. (1995) presented 2 unrelated cases with a typical picture of Fryns syndrome but without diaphragmatic hernia. One of these patients was alive at the age of 14 months, but was severely retarded. Bamforth et al. (1987) and Hanssen et al. (1992) also described patients with this syndrome who survived the neonatal period. In the report of Hanssen et al. (1992), 2 older sibs had died in utero. The reports suggested that survival beyond the neonatal period is possible when the diaphragmatic defect and lung hypoplasia are not present. However, mental retardation has been present in all surviving patients.

- Vargas et al. (2000) reported a pair of monozygotic twins with Fryns syndrome discordant for severity of diaphragmatic defect. Both twins had macrocephaly, coarse facial appearance, hypoplasia of distal phalanges, and an extra pair of ribs. Twin A lacked an apparent diaphragmatic defect, and at 1 year of age had mild developmental delay. Twin B had a left congenital diaphragmatic hernia and died neonatally. The authors suggested that absence of diaphragmatic defect in Fryns syndrome may represent a subpopulation of more mildly affected patients.

- Aymé, "et al." (1989) described 8 cases of Fryns syndrome in France. The most frequent anomalies were diaphragmatic defects, lung hypoplasia, cleft lip and palate, cardiac defects, including septal defects and aortic arch anomalies, renal cysts, urinary tract malformations, and distal limb hypoplasia. Most patients also had hypoplastic external genitalia and anomalies of internal genitalia, including bifid or hypoplastic uterus or immature testes. The digestive tract was also often abnormal; duodenal atresia, pyloric hyperplasia, malrotation and common mesentery were present in about half of the patients. When the brain was examined, more than half were found to have Dandy–Walker anomaly and/or agenesis of the corpus callosum. A few patients demonstrated cloudy cornea. Histologically, 2 of 3 patients showed retinal dysplasia with rosettes and gliosis of the retina, thickness of the posterior capsule of the lens, and irregularities of Bowman membrane.

- Alessandri et al. (2005) reported a newborn from the Comores Islands with clinical features of Fryns syndrome without diaphragmatic hernia. They noted that diaphragmatic hernia is found in more than 80% of cases and that at least 13 other cases had been reported with an intact diaphragm.

- In a postneonatal survivor of Fryns syndrome, Riela et al. (1995) described myoclonus appearing shortly after birth, which was well controlled on valproate. Progressive cerebral and brainstem atrophy was noted on serial MRIs made at 3 months and after 6 months of age.

- Van Hove et al. (1995) described a boy with Fryns syndrome who survived to age 3 years and reviewed the outcome of other reported survivors (approximately 14% of reported cases). Survivors tended to have less frequent diaphragmatic hernia, milder lung hypoplasia, absence of complex cardiac malformation, and severe neurologic impairment. Their patient had malformations of gyration and sulcation, particularly around the central sulcus, and hypoplastic optic tracts beyond the optic chiasm associated with profound mental retardation.

- Fryns and Moerman (1998) reported a second-trimester male fetus with Fryns syndrome and midline scalp defects. The authors stated that the finding of a scalp defect in Fryns syndrome confirms that it is a true malformation syndrome with major involvement of the midline structures.

- Ramsing et al. (2000) described 2 sibships with 4 fetuses and 1 preterm baby of 31 weeks' gestation affected by a multiple congenital disorder suggestive of Fryns syndrome. In addition to the diaphragmatic defects and distal limb anomalies, they presented with fetal hydrops, cystic hygroma, and multiple pterygias. Two affected fetuses in 1 family showed severe craniofacial abnormalities with bilateral cleft lip and palate and cardiovascular malformation.

- Arnold et al. (2003) reported a male fetus with Fryns syndrome and additional abnormalities, in particular, multiple midline developmental defects including gastroschisis, central nervous system defects with left arrhinencephaly and cerebellar hypoplasia, midline cleft of the upper lip, alveolar ridge, and maxillary bone, and cleft nose with bilateral choanal atresia.

- Pierson et al. (2004) reviewed 77 reported patients with Fryns syndrome and summarized the abnormal eye findings identified in 12 of them. They also described 3 new patients with Fryns syndrome, 1 of whom demonstrated unilateral microphthalmia and cloudy cornea.

- Slavotinek et al. (2005) noted that Fryns syndrome may be the most common autosomal recessive syndrome in which congenital diaphragmatic hernia (see DIH2, 222400) is a cardinal feature. The autosomal recessive inheritance in Fryns syndrome contrasts with the sporadic inheritance for most patients with DIH.

In right atrial isomerism, both atria of the heart are morphological right atria leading to associated abnormalities in the pulmonary venous system. In addition, individuals with right atrial isomerism develop asplenia, a midline liver, malrotation of the small intestine and the presence of two morphologic right lungs. Individuals with left atrial isomerism, by comparison, have two morphologic left atria, polysplenia, intestinal malrotation and two morphologic left lungs.

The majority of cases present at the time of birth or within a few days or weeks. Presenting signs and symptoms of the congenital heart defect may include cyanosis, breathlessness, lethargy and poor feeding.

Genitopatellar syndrome is a rare condition characterized by genital abnormalities, missing or underdeveloped kneecaps (patellae), intellectual disability, and abnormalities affecting other parts of the body.

Genitopatellar syndrome is also associated with delayed development and intellectual disability, which are often severe. Affected individuals may have an unusually small head (microcephaly) and structural brain abnormalities, including underdeveloped or absent tissue connecting the left and right halves of the brain (agenesis of the corpus callosum).

Causes a ‘white reflex’ in the affected eye (leukocoria), prompting further investigation.

Genitopatellar syndrome is a rare disorder with characteristic craniofacial features, congenital flexion contractures of the lower limbs, absent or abnormal patellae, urogenital anomalies, and severe psychomotor retardation.

In 2012, it was shown that mutations in the gene KAT6B cause the syndrome.

Heart-hand syndromes are a group of rare diseases that manifest with both heart and limb deformities.

, known heart-hand syndromes include Holt–Oram syndrome, Berk–Tabatznik syndrome, heart-hand syndrome type 3, brachydactyly-long thumb syndrome, patent ductus arteriosus-bicuspid aortic valve syndrome and heart hand syndrome, Slovenian type.

The clinical presentation is variable but includes

- developmental and growth delay

- athletic muscular built

- skeletal anomalies

- joint stiffness

- characteristic facial appearance

- deafness

- variable cognitive deficits

- tracheal stenosis

- aortic stenosis

- pyloric stenosis

The facial abnormalities include:

- blepharophimosis (an abnormally narrow gap between the upper and lower eyelids)

- maxillary hypoplasia (underdevelopment of the upper jaw)

- prognathism (prominent lower jaw)

The skeletal abnormalities include:

- short stature

- square body shape

- broad ribs

- iliac hypoplasia

- brachydactyly

- flattened vertebrae

- thickened calvaria

Congenital heart disease and undescended testes have also been reported in association with this syndrome.

Numerous associated abnormalities of other organ systems may be present. This heterogeneity requires comprehensive evaluation of all patients and treatment regimes that can vary from modification of activities to extensive spinal surgeries. Furthermore, it is unclear whether Klippel–Feil syndrome is a unique disease, or if it is one part of a spectrum of congenital spinal deformities. Klippel–Feil syndrome is usually diagnosed after birth.

The most common sign of the disorder is restricted mobility of the neck and upper spine. A short neck and low hairline at the back of the head may occur in some patients.

Associated abnormalities may include:

- scoliosis (side-to-side curvature of the spine), which is abnormal curving of the spine. The spine sometimes appears as a "C" or an "S"

- spina bifida, when the spinal canal and the back bone do not close completely during birth

- anomalies of the kidneys and the ribs

- cleft palate (hole in the roof of the mouth)

- dental problems (late dentition, high-risk of caries, oligo- and hypodontia)

- respiratory problems

- heart malformations

- short stature

- Duane syndrome

- Approximately 35% of patients with Klippel–Feil syndrome will also have a congenital elevation of the scapula known as Sprengel's deformity

The disorder also may be associated with abnormalities of the head and face, skeleton, sex organs, muscles, brain and spinal cord, arms, legs, fingers and heart defects. These heart defects often lead to a shortened life expectancy, the average being 35–45 years of age among males and 40–50 among females. This condition is similar to the heart failure seen in gigantism.

In 2011, a study identifying the occurrence of symptoms of 100 patients was published.

Up to ~85% of people with NS have one of the following heart defects:

- Pulmonary valvular stenosis (50–60%)

- Septal defects: atrial (10–25%) or ventricular (5–20%)

- Hypertrophic cardiomyopathy (12–35%)

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.

Nance–Horan syndrome is a rare X linked syndrome characterized by congenital cataract leading to profound vision loss, characteristic dysmorphic features and dental anomalies. Microcornea, microphthalmia and mild or moderate mental retardation may accompany these features. Heterozygous females often manifest similarly but with less severe features than affected males.

Vascular tumors, often referred to as hemangiomas, are the most common tumors in infants, occurring in 1-2%. Prevalence is even higher (10%) in premature infants of very low birth weight. Vascular tumors are characterized by overgrowth of normal vessels, which show increased endothelial proliferation. It can be present at birth, but often appears within a couple of weeks after birth or during infancy. There are different kinds of vascular tumors, but the 4 most common types are: infantile hemangioma, congenital hemangioma, kaposiform hemangioendothelioma and pyogenic granuloma.

People with visible marks generally feel fine (physically) and can act normally, but when it is mentioned, they may become withdrawn and self-conscious. Some children may have low self-esteem due to the condition.

CMTC is an uncommon, sporadic congenital vascular malformation characterized by a generalized or localized reticulated cutaneous vascular network.

Cutaneous lesions described in patients with CMTC include nevus flammeus, hemangioma, nevus anemicus, café-au-lait spots, melanocytic nevus, aplasia cutis and acral cyanosis.

It has a marbled bluish to deep-purple appearance. The dark skin lesions often show a palpable loss of dermal substance. The reticulated mottling frequently appears more prominent in a cold environment (physiologic cutis marmorata), but tends not to disappear with warming. Hence, the erythema may be worsened by cooling, physical activity, or crying.

CMTC frequently involves the extremities, with the lower extremities involved most commonly, followed by the upper extremities, and then the trunk and face. The lower extremities often show atrophy and seldom show hypertrophy resulting in limb circumference discrepancy.

When located on the trunk, the lesions of CMTC tend to show mosaic distribution in streaks with a sharp midline demarcation seen across the abdomen. The lesions are primarily localized, but can be segmental or generalized, often unilateral in appearance. Diffuse involvement of the skin is usually not observed.

Although its course is variable, the majority of lesions in mild cases fade by adolescence. Ulceration and secondary infection are complications in severe cases and can be fatal if present in the neonatal period.

Anatomical changes associated with this disorder includes:

- single artery arising from the two ventricles which gives rise to both the aortic and pulmonary vessels

- abnormal truncal valve

- right sided aortic arch in about 30% of cases (not shown)

- large ventricular septal defect

- pulmonary hypertension

- complete mixing occurring at level of the great vessel

- right-to-left shunting of blood

Heart-hand syndrome type 1 is more commonly known as Holt–Oram syndrome. Is the most prevalent form of heart-hand syndrome.

It is an autosomal dominant disorder that affects bones in the arms and hands (the upper limbs) and may also cause heart problems. The syndrome includes an absent radial bone in the arms, an atrial septal defect, and a first degree heart block.