There is considerable variability in the phenotype of Loeys–Dietz syndrome, from mild features to severe systemic abnormalities. The primary manifestations of Loeys–Dietz syndrome are arterial tortuosity (winding course of blood vessels), widely spaced eyes (hypertelorism), wide or split uvula, and aneurysms at the aortic root. Other features may include cleft palate and a blue/gray appearance of the white of the eyes. Cardiac defects and club foot may be noted at birth.

There is overlap in the manifestations of Loeys–Dietz and Marfan syndromes, including increased risk of ascending aortic aneurysm and aortic dissection, abnormally long limbs and fingers, and dural ectasia (a gradual stretching and weakening of the dura mater that can cause abdominal and leg pain). Findings of hypertelorism (widely spaced eyes), bifrid or split uvula, and skin findings such as easy bruising or abnormal scars may distinguish Loys-Dietz from Marfan syndrome.

Findings of Loys-Dietz syndrome may include:

- Skeletal/spinal malformations: craniosynositosis, Scoliosis, spinal instability and spondylolisthesis, Kyphosis

- Sternal abnormalities: pectus excavatum, pectus carinatum

- Contractures of fingers and toes (camptodactyly)

- Long fingers and lax joints

- Weakened or missing eye muscles (strabismus)

- Club foot

- Premature fusion of the skull bones (craniosynostosis)

- Joint hypermobility

- Congenital heart problems including patent ductus arteriosus (connection between the aorta and the lung circulation) and atrial septal defect (connection between heart chambers)

- Translucency of the skin with velvety texture

- Abnormal junction of the brain and medulla (Arnold-Chiari malformation)

- Bicuspid aortic valves

- Criss-crossed pulmonary arteries

It is characterized by developmental defects including cryptophthalmos (where the eyelids fail to separate in each eye), and malformations in the genitals (such as micropenis, cryptorchidism or clitoromegaly). Congenital malformations of the nose, ears, larynx and renal system, as well as mental retardation, manifest occasionally. Syndactyly (fused fingers or toes) has also been noted.

There is no specific treatment or cure for individuals affected with this type of syndrome, though some of the abnormal physical features may be surgically correctable.

There is a range of signs and symptoms including cleft lip or palate, mental retardation and various forms of ectodermal dysplasia. Additional symptoms may include fused eyelids, absent nails, delayed bone growth and dry skin. It is believed that this syndrome follows an autosomal dominant pattern of inheritance with incomplete penetrance, and caused by a mutation affecting the TP63 gene. It has been suggested that this syndrome, AEC syndrome and Rapp–Hodgkin syndrome may be variations of the same disease.

People with Aarskog-Scott syndrome often have distinctive facial features, such as widely spaced eyes (hypertelorism), a small nose, a long area between the nose and mouth (philtrum), and a widow's peak hairline. They frequently have mild to moderate short stature during childhood, but their growth usually catches up with that of their peers during puberty. Hand abnormalities are common in this syndrome and include short fingers (brachydactyly), curved pinky fingers (fifth finger clinodactyly), webbing of the skin between some fingers (cutaneous syndactyly), and a single crease across the palm. Other abnormalities in people with Aarskog-Scott syndrome include heart defects and a split in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).

Most males with Aarskog-Scott syndrome have a shawl scrotum, in which the scrotum surrounds the penis instead of hanging below. Less often, they have undescended testes (cryptorchidism) or a soft out-pouching around the belly-button (umbilical hernia) or in the lower abdomen (inguinal hernia).

The intellectual development of people with Aarskog-Scott syndrome varies widely. Some may have mild learning and behavior problems, while others have normal intelligence. In rare cases, severe intellectual disability has been reported.

The key affected features of this condition are described in its name.

Scalp: There are raised nodules over the posterior aspect of the scalp, covered by scarred non-hair bearing skin.

Ears: The shape of the pinnae is abnormal, with the superior edge of the pinna being turned over more than usual. The size of the tragus, antitragus and lobule may be small.

Nipples: The nipples are absent or rudimentary. The breasts may be small or virtually absent.

Other features of the condition include:

Dental abnormalities: missing or widely spaced teeth

Syndactyly: toes or fingers may be partially joined proximally

Renal abnormalities: renal hypoplasia, pyeloureteral duplication

Eye abnormalities: Cataract, coloboma of the iris and asymmetric pupils.

Klippel–Trénaunay syndrome (KTS or KT), formerly Klippel–Trénaunay–Weber syndrome and sometimes angioosteohypertrophy syndrome and hemangiectatic hypertrophy, is a rare congenital medical condition in which blood vessels and/or lymph vessels fail to form properly. The three main features are nevus flammeus (port-wine stain), venous and lymphatic malformations, and soft-tissue hypertrophy of the affected limb. It is similar to, though distinctly separate from, the less common Parkes-Weber syndrome.

The classical triad of Klippel-Trenaunay syndrome consists of:

1. vascular malformations of the capillary, venous and lymphatic vessels;

2. varicosities of unusual distribution, particularly the lateral venous anomaly; and

3. unilateral soft and skeletal tissue hypertrophy, usually the lower extremity.

Of those fetuses that do survive to gestation and subsequent birth, common abnormalities may include:

- Nervous system

- Intellectual disability and motor disorder

- Microcephaly

- Holoprosencephaly (failure of the forebrain to divide properly).

- Structural eye defects, including microphthalmia, Peters' anomaly, cataract, iris or fundus (coloboma), retinal dysplasia or retinal detachment, sensory nystagmus, cortical visual loss, and optic nerve hypoplasia

- Meningomyelocele (a spinal defect)

- Musculoskeletal and cutaneous

- Polydactyly (extra digits)

- Cyclopia

- Proboscis

- Congenital trigger digits

- Low-set ears

- Prominent heel

- Deformed feet known as rocker-bottom feet

- Omphalocele (abdominal defect)

- Abnormal palm pattern

- Overlapping of fingers over thumb

- Cutis aplasia (missing portion of the skin/hair)

- Cleft palate

- Urogenital

- Abnormal genitalia

- Kidney defects

- Other

- Heart defects (ventricular septal defect) (Patent Ductus Arteriosus)

- Dextrocardia

- Single umbilical artery

The following is a list of symptoms that have been associated with Roberts syndrome:

- Bilateral Symmetric Tetraphocomelia- a birth defect in which the hands and feet are attached to shortened arms and legs

- Prenatal Growth Retardation

- Hypomelia (Hypoplasia)- the incomplete development of a tissue or organ; less drastic than aplasia, which is no development at all

- Oligodactyly- fewer than normal number of fingers or toes

- Thumb Aplasia- the absence of a thumb

- Syndactyly- condition in which two or more fingers (or toes) are joined together; the joining can involve the bones or just the skin between the fingers

- Clinodactyly- curving of the fifth finger (little finger) towards the fourth finger (ring finger) due to the underdevelopment of the middle bone in the fifth finger

- Elbow/Knee Flexion Contractures- an inability to fully straighten the arm or leg

- Cleft Lip- the presence of one or two vertical fissures in the upper lip; can be on one side (unilateral) or on both sides (bilateral)

- Cleft Palate- opening in the roof of the mouth

- Premaxillary Protrusion- upper part of the mouth sticks out farther than the lower part of the mouth

- Micrognathia- small chin

- Microbrachycephaly- smaller than normal head size

- Malar Hypoplasia- underdevelopment of the cheek bones

- Downslanting Palpebral Fissures- the outer corners of the eyes point downwards

- Ocular Hypertelorism- unusually wide-set eyes

- Exophthalmos- a protruding eyeball

- Corneal Clouding- clouding of the front-most part of the eye

- Hypoplastic Nasal Alae- narrowing of the nostrils that can decrease the width of the nasal base

- Beaked Nose- a nose with a prominent bridge that gives it the appearance of being curved

- Ear Malformations

- Intellectual disability

- Encephalocele (only in severe cases)- rare defect of the neural tube characterized by sac-like protrusions of the brain

Mortality is high among those severely affected by Roberts syndrome; however, mildly affected individuals may survive to adulthood

Since the original identification of Schimmelpenning syndrome, the number of findings has expanded to the point that the syndrome is associated with a considerable constellation of abnormalities. The abnormalities may occur in a variety of combinations, and need not include all three aspects of the classic triad of sebaceous nevus, seizures and mental retardation. In 1998, a literature review by van de Warrenburg et al. found:

- seizures in 67% of cases

- mental retardation in 61% of cases

- ophthalmological abnormalities in 59% of cases

- involvement of other organ systems in 61% of cases

- structural abnormality of cerebrum or cranium in 72% of cases

The major neurological abnormalities include mental retardation to varying extent, seizures, and hemiparesis. Seizures, when present, typically begin during the first year of life. The most common structural central nervous system abnormalities in Schimmelpenning syndrome are hemimegalencephaly and ipselateral gyral malformations.

The major ocular abnormalities are colobomas and choristomas.

Skeletal abnormalities may include dental irregularities, scoliosis, vitamin D-resistant rickets and hypophosphatemia. Cardiovascular abnormalities include ventricular septal defect and co-arctation of the aorta; urinary system issues include horseshoe kidney and duplicated urinary collection system.

Little is known about the natural history of Roberts syndrome due to its wide clinical variability. The prognosis of the disease depends on the malformations, as the severity of the malformations correlates with survival. The cause of death for most fatalities of Roberts syndrome have not been reported; however, five deaths were reportedly due to infection.

The following are observations that have been made in individuals with cytogenetic findings of PCS/HR or ESCO2 mutations:

- The symptom of prenatal growth retardation is the most common finding and can be moderate to severe. Postnatal growth retardation can also be moderate to severe and correlates with the degree of severity of limb and craniofacial malformations.

- In limb malformations, the upper limbs are typically more severely affected than the lower limbs. There have been many cases of only upper limb malformation.

- In hand malformations, the thumb is most often affected, followed by the fifth finger (the little finger). In severe cases, the patient may only have three fingers and in rare cases only one.

- In craniofacial malformations, mildly affected individuals will have no abnormalities of the palate. The most severely affected will have a fronto-ethmoid-nasal-maxillary encephalocele.

- The severity of limb malformations and craniofacial malformations is correlated.

- Other abnormalities can occur in different parts of the body, including:

- Heart- atrial septal defects, ventricular septal defects, patent ductus arteriosus

- Kidneys- polycystic kidney, horseshoe kidney

- Male Genitals- enlarged penis, cryptorchidism

- Female Genitals- enlarged clitoris

- Hair- sparse, silvery-blonde scalp hair

- Cranial Nerve Paralysis, Moyamoya disease, Stroke, Intellectual disability

Pashayan syndrome also known as Pashayan–Prozansky Syndrome, and blepharo-naso-facial syndrome is a rare syndrome. Facial abnormalities characterise this syndrome as well as malformation of extremities. Specific characteristics would be a bulky, flattened nose, where the face has a mask like appearance and the ears are also malformed.

A subset of Pashayan syndrome has also been described, known as "cerebrofacioarticular syndrome", "Van Maldergem syndrome'" or "Van Maldergem–Wetzburger–Verloes syndrome". Similar symptoms are noted in these cases as in Pashayan syndrome.

One of the most prominent and visible symptoms of Nevo Syndrome is the prenatal overgrowth, which continues into the infant and toddler stage. This excessive weight gain can be attributed to the low concentrations of growth hormone and insulin growth factor that are normally present to regulate weight gain. Other common symptoms associated with Nevo Syndrome are the outward wrist-drop, edema in hands and feet, undescended testes, low-set ears, hypotonia, the presence of low muscle tone in children, and long tapered fingers, and a highly arched palate.

Fraser syndrome (also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome) is an autosomal recessive congenital disorder. Fraser syndrome is named for the geneticist George R. Fraser, who first described the syndrome in 1962.

Bannayan–Riley–Ruvalcaba syndrome is associated with enlarged head and benign mesodermal hamartomas (multiple hemangiomas, and intestinal polyps). Dysmorphy as well as delayed neuropsychomotor development can also be present. The head enlargement does not cause widening of the ventricles or raised intracranial pressure; these individuals have a higher risk of developing tumors, as the gene involved in BRRs is phosphatase and tensin homologue.

Some individuals have thyroid issues consistent with multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer,

most lesions are slowly growing. Visceral as well as intracranial involvement may occur in some cases, and can cause bleeding and symptomatic mechanical compression

Aarskog–Scott syndrome is a rare disease inherited as X-linked and characterized by short stature, facial abnormalities, skeletal and genital anomalies. This condition mainly affects males, although females may have mild features of the syndrome.

The Aarskog–Scott syndrome (AAS) is also known as the Aarskog syndrome, faciodigitogenital syndrome, shawl scrotum syndrome and faciogenital dysplasia.

The classical triad of symptoms that defines 3C syndrome includes certain heart defects, hypoplasia (underdevelopment) of the cerebellum, and cranial dysmorphisms, which can take various forms. The heart defects and cranial dysmorphisms are heterogeneous in individuals who are all classed as having Ritscher-Schinzel syndrome.

Heart defects commonly seen with Ritscher-Schinzel syndrome are associated with the endocardial cushion and are the most important factor in determining a diagnosis. The mitral valve and tricuspid valve of the heart can be malformed, the atrioventricular canal can be complete instead of developing into the interatrial septum and interventricular septum, and conotruncal heart defects, which include tetralogy of Fallot, double outlet right ventricle, transposition of the great vessels, and hypoplastic left heart syndrome. Aortic stenosis and pulmonary stenosis have also been associated with 3C syndrome.

The cranial dysmorphisms associated with 3C syndrome are heterogeneous and include a degree of macrocephaly, a large anterior fontanel, a particularly prominent occiput and forehead, ocular hypertelorism (wide-set eyes), slanted palpebral fissures, cleft palate, a depressed nasal bridge, cleft palate with associated bifid uvula, low-set ears, micrognathia (an abnormally small jaw), brachycephaly (flattened head), and ocular coloboma. Low-set ears are the most common cranial dysmorphism seen in 3C syndrome, and ocular coloboma is the least common of the non-concurrent symptoms (cleft lip co-occurring with cleft palate is the least common).

Cranial dysplasias associated with 3C syndrome are also reflected in the brain. Besides the cerebellar hypoplasia, cysts are commonly found in the posterior cranial fossa, the ventricles and the cisterna magna are dilated/enlarged, and Dandy-Walker malformation is present. These are reflected in the developmental delays typical of the disease. 75% of children with 3C syndrome have Dandy-Walker malformation and hydrocephalus.

Signs and symptoms in other body systems are also associated with 3C syndrome. In the skeletal system, ribs may be absent, and hemivertebrae, syndactyly (fusion of fingers together), and clinodactyly (curvature of the fifth finger) may be present. In the GI and genitourinary systems, anal atresia, hypospadia (misplaced urethra), and hydronephrosis may exist. Adrenal hypoplasia and growth hormone deficiency are associated endocrine consequences of Ritscher-Schinzel syndrome. Some immunodeficiency has also been reported in connection with 3C syndrome.

Many children with the disorder die as infants due to severe congenital heart disease. The proband of Ritscher and Schinzel's original study was still alive at the age of 21.

A fetus with 3C syndrome may have an umbilical cord with one umbilical artery instead of two.

The birth defect is diagnosed by the presence of a combination of these symptoms (often on approximately ¼ of the body, though some cases may present more or less affected tissue):

- One or more distinctive port-wine stains with sharp borders

- Varicose veins

- Hypertrophy of bony and soft tissues, that may lead to local gigantism or shrinking, most typically in the lower body/legs.

- An improperly developed lymph system

In some cases, port-wine stains (capillary port wine type) may be absent. Such cases are very rare and may be classified as "atypical Klippel–Trenaunay syndrome".

KTS can either affect blood vessels, lymph vessels, or both. The condition most commonly presents with a mixture of the two. Those with venous involvement experience increased pain and complications, such as venous ulceration in the lower extremities.

Those with large AVMs are at risk of formation of blood clots in the vascular lesion, which may migrate to the lungs (pulmonary embolism). If there is large-volume blood flow through the lesion, "high-output heart failure" may develop due to the inability of the heart to generate sufficient cardiac output.

Overgrowth syndromes in children constitute a group of rare disorders that are typical of tissue hypertrophy. Individual overgrowth syndromes have been shown to overlap with regard to clinical and radiologic features. The details of the genetic bases of these syndromes are unfolding. Any of the three embryonic tissue layers may be involved.The syndromes may manifest in localized or generalized tissue overgrowth. Latitudinal and longitudinal growth may be affected. Nevertheless, the musculoskeletal features are central to the diagnosis of some syndromes such as Proteus syndrome. The time of presentation of children with overgrowth syndromes is an important contributor to the differential diagnosis. Children with some overgrowth syndromes such as Klippel-Trenaunay-Weber syndrome can be readily detectable at birth. In contrast other overgrowth syndromes such as Proteus syndrome usually present in the postnatal period characteristically between the 2nd and 3rd year of life. In general, children with overgrowth syndromes are at increased risk of embryonic tumor development.

Examples of overgrowth syndromes include; Beckwith-Wiedemann syndrome, Proteus syndrome, Sotos syndrome, neurofibromatosis, Simpson-Golabi-Behmel syndrome, Weaver syndrome, Sturge–Weber syndrome, Macrocephaly-capillary malformation, CLOVES syndrome, fragile X syndrome and Klippel-Trenaunay-Weber syndrome.

All people with this disorder have at least one limb abnormality that affects bones in the wrist (carpal bones). Often, these wrist bone abnormalities can be detected only by X-ray. Affected individuals may have additional bone abnormalities that can include polydactyly, a hypoplastic thumb or a Triphalangeal thumb, partial or complete absence of bones in the forearm, an underdeveloped Humerus, and abnormalities that affect the Clavicle and Scapula. Bone abnormalities may affect each arm differently, and the left side can be affected more than the right side. In some cases, only one arm and/or hand is affected.

About 75 percent of individuals with Holt–Oram syndrome have heart problems. The most common problem is a defect in the muscular wall, or septum, that separates the right and left sides of the heart (atria). Atrial septal defects (ASD) are caused by a hole in the septum between the left and right upper chambers of the heart (atria), and ventricular septal defects (VSD) are caused by a hole in the septum between the left and right lower chambers of the heart (ventricles). Sometimes people with Holt–Oram syndrome have cardiac conduction disease, which is caused by abnormalities in the electrical system that coordinates contractions of the heart chambers. Cardiac conduction disease can lead to problems such as a slow heart rate (bradycardia) or a rapid and ineffective contraction of the heart muscles (fibrillation). Cardiac conduction disease can occur along with other heart defects (such as septal defects) or as the only heart problem in people with Holt–Oram syndrome.

The syndrome is a rare clinical disorder.

- Physical

- Overgrowth

- Accelerated skeletal maturation

- Dysmorphic facial features

- Prominent eyes

- Bluish sclerae

- Coarse eyebrows

- Upturned nose

- Radiologic examination

- Accelerated osseous maturation

- Phalangeal abnormalities

- Tubular thinning of the long bones

- Skull abnormalities

- Mental

- Often associated with intellectual disability (of variable degree)

Loeys–Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has features similar to Marfan syndrome and Ehlers–Danlos syndrome. The disorder is marked by aneurysms in the aorta, often in children, and the aorta may also undergo sudden dissection in the weakened layers of the wall of aorta. Aneurysms and dissections also can occur in arteries other than the aorta. Because aneurysms in children tend to rupture early, children are at greater risk for dying if the syndrome is not identified. Surgery to repair aortic aneurysms is essential for treatment.

There are four types of the syndrome, labelled types I through IV, which are distinguished by their genetic cause. Type 1, Type 2, Type 3, and Type 4 are caused by mutations in "TGFBR1", "TGFBR2", "SMAD3", and "TGFB2" respectively. These four genes encoding transforming growth factors play a role in cell signaling that promotes growth and development of the body's tissues. Mutations of these genes cause production of proteins without function. Although the disorder has an autosomal pattern of inheritance, this disorder results from a new gene mutation in 75% of cases and occurs in people with no history of the disorder in their family.

Loeys-Dietz syndrome was identified and characterized by pediatric geneticists Bart Loeys and Harry Dietz at Johns Hopkins University in 2005.

Multiple hamartoma syndrome is a syndrome characterized by more than one hamartoma.

It is sometimes equated with Cowden syndrome. However, MeSH also includes Bannayan–Zonana syndrome (that is, Bannayan–Riley–Ruvalcaba syndrome) and Lhermitte–Duclos disease under this description. Some articles include Cowden syndrome, Bannayan–Riley–Ruvalcaba syndrome, and at least some forms of Proteus syndrome and Proteus-like syndrome under the umbrella term PTEN hamartoma tumor syndromes (PHTS).

Scalp–ear–nipple syndrome (also known as "Finlay–Marks syndrome") is a condition associated with aplasia cutis congenita.

The RASopathies are developmental syndromes caused by germline mutations (or in rare cases by somatic mosaicism) in genes that alter the Ras subfamily and mitogen-activated protein kinases that control signal transduction, including:

- Capillary malformation-AV malformation syndrome

- Autoimmune lymphoproliferative syndrome

- Cardiofaciocutaneous syndrome

- Hereditary gingival fibromatosis type 1

- Neurofibromatosis type 1

- Noonan syndrome

- Costello syndrome, Noonan-like

- Legius syndrome, Noonan-like

- Noonan syndrome with multiple lentigines, formerly called LEOPARD syndrome, Noonan-like