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.

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.

Ulnar polydactyly is often bilateral and associated with syndactyly and polydactyly of the feet. This can be a simple or complex polydactyly. Ulnar polydactyly occurs as an isolated congenital condition, but can also be part of a syndrome. The syndromes which occur with ulnar polydactyly are: Greig cephalopolysyndactyly syndrome, Meckel syndrome, Ellis–van Creveld syndrome, McKusick–Kaufman syndrome, Down syndrome, Bardet–Biedl syndrome, Smith–Lemli–Opitz syndrome

This is a very rare situation, in which the extra digit is on the ring, middle or index finger. Of these fingers, the index finger is most often affected, whereas the ring finger is rarely affected.

This type of polydactyly can be associated with syndactyly, cleft hand and several syndromes.

Polysyndactyly presents various degrees of syndactyly affecting fingers three and four.

The cranium consists of three main sections including the base of the cranium (occipital bone), the face (frontal bone), and the top (parietal bones) and sides (temporal bone) of the head. Most of the bones of the cranium are permanently set into place prior to birth. However, the temporal and parietal bones are separated by sutures, which remain open, allowing the head to slightly change in shape during childbirth. The cranial sutures eventually close within the first couple of years following birth, after the brain has finished growing.

In individuals with SCS, the coronal suture separating the frontal bones from the parietal bones, closes prematurely (craniosynostosis), occasionally even before birth. If the coronal suture closes asymmetrically or unilaterally, then the face and forehead will form unevenly, from side-to-side. People with SCS have pointy, tower-like heads because their brain is growing faster than their skull, resulting in increased intracranial pressure (ICP) and causing the top of the head and/or forehead to bulge out to allow for brain growth. The face appears uneven, particularly in the areas of the eyes and cheeks, and the forehead appears wide and tall.

Because of the abnormal forehead, there is less space for the normal facial features to develop. This results in shallow eye sockets and flat cheekbones. The shallow eye sockets make the eyes more prominent or bulging and cause the eyes to be more separated than normal (hypertelorism). The underdeveloped eye sockets, cheekbones, and lower jaw cause the face to appear flat. Furthermore, the minor downward slant of the eyes along with the drooping eyelids (ptosis) adds to the overall unevenness of the face.

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.

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.

Ectrodactyly, split hand, cleft hand, derived from the Greek "ektroma" (abortion) and "daktylos" (finger) involves the deficiency or absence of one or more central digits of the hand or foot and is also known as split hand/split foot malformation (SHFM). The hands and feet of people with ectrodactyly are often described as "claw-like" and may include only the thumb and one finger (usually either the little finger, ring finger, or a syndactyly of the two) with similar abnormalities of the feet.

It is a rare form of a congenital disorder in which the development of the hand is disturbed. It is a type I failure of formation – longitudinal arrest. The central ray of the hand is affected and usually appears without proximal deficiencies of nerves, vessels, tendons, muscles and bones in contrast to the radial and ulnar deficiencies. The cleft hand appears as a V-shaped cleft situated in the centre of the hand. The digits at the borders of the cleft might be syndactilyzed, and one or more digits can be absent. In most types, the thumb, ring finger and little finger are the less affected parts of the hand. The incidence of cleft hand varies from 1 in 90,000 to 1 in 10,000 births depending on the used classification. Cleft hand can appear unilateral or bilateral, and can appear isolated or associated with a syndrome.

Split hand/foot malformation (SHFM) is characterized by underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits. SHFM is a heterogeneous condition caused by abnormalities at one of multiple loci, including SHFM1 (SHFM1 at 7q21-q22), SHFM2 (Xq26), SHFM3 (FBXW4/DACTYLIN at 10q24), SHFM4 (TP63 at 3q27), and SHFM5 (DLX1 and DLX 2 at 2q31). SHFM3 is unique in that it is caused by submicroscopic tandem chromosome duplications of FBXW4/DACTYLIN. SHFM3 is considered 'isolated' ectrodactyly and does not show a mutation of the tp63 gene.

People with the combination of Duane anomaly and radial ray malformations may have a variety of other signs and symptoms. These features include:

- Unusually shaped ears

- Hearing loss

- Heart and kidney defects

- A distinctive facial appearance

- An inward- and downward-turning foot (a clubfoot)

- Fused vertebrae.

Sugarman syndrome is the common name of autosomal recessive oral-facial-digital syndrome type III, one of ten distinct genetic disorders that involve developmental defects to the mouth.

Alternative names for this condition include: Brachydactyly of the hands and feet with duplication of the first toes, Sugarman brachydactyly and Brachydactyly with major proximal phalangeal shortening.

This is characterized by hand and arm abnormalities. The following are specific characteristics:

- Malformed or absent (aplasia) thumb

- A thumb that looks more like a finger

- Partial or complete absence of a radius

- Shortening and radial deviation of the forearms

- Triphalangeal thumb

- Duplication of the thumb (preaxial polydactyly)

Individuals with SCS are all affected differently. Even within the same family, affected individuals have different features. The majority of individuals with SCS are moderately affected, with uneven facial features and a relatively flat face due to underdeveloped eye sockets, cheekbones, and lower jaw. In addition to the physical abnormalities, people with SCS also experience growth delays, which results in a relatively short stature. Although, most individuals with SCS are of normal intelligence, some individuals may have mild to moderate mental retardation (IQ from 50-70). More severe cases of SCS, with more serious facial deformities, occurs when multiple cranial sutures close prematurely.

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

The three most common symptoms of Opitz G/BBB syndrome (both type I & II) are hypertelorism (exceptionally wide-spaced eyes), laryngo-tracheo-esophalgeal defects (including clefts and holes in the palate, larynx, trachea and esophagus) and hypospadias (urinary openings in males not at the tip of the penis) (Meroni, Opitz G/BBB syndrome, 2012). Abnormalities in the larynx, trachea and esophagus can cause significant difficulty breathing and/or swallowing and can result in reoccurring pneumonia and life-threatening situations. Commonly, there may be a gap between the trachea and esophagus, referred to as a laryngeal cleft; which can allow food or fluid to enter the airway and make breathing and eating a difficult task.

Genital abnormalities like a urinary opening under the penis (hypospadias), undescended testes (cryptorchidism), underdeveloped scrotum and a scrotum divided into two lobes (bifid scrotum) can all be commonplace for males with the disease.

Developmental delays of the brain and nervous system are also common in both types I and II of the disease. 50% of people with Opitz G/BBB Syndrome will experience developmental delay and mild intellectual disability. This can impact motor skills, speech and learning capabilities. Some of these instances are likened to autistic spectrum disorders. Close to half of the people with Opitz G/BBB Syndrome also have a cleft lip (hole in the lip opening) and possibly a cleft palate (hole in the roof of the mouth), as well. Less than half of the people diagnosed have heart defects, imperforate anus (obstructed anal opening), and brain defects. Of all the impairments, female carriers of X-linked Type I Opitz G/BBB Syndrome usually only have ocular hypertelorism.

In HWS the hair is coarse and sparse, eyelashes are sparse or absent, nails may be absent or malformed, and teeth may be small and malformed. There may be fewer than normal sweat glands and they may produce little sweat, a condition known generally as hypohidrosis. Chronic inflammatory dermatitis of the scalp is a common symptom.

Two features differentiate HWS from other ectodermal displasias. First, the syndrome is associated with cleft palate, and, less often, cleft lip. Second, the edges of the upper and lower eyelid grow bands of fibrous tissue, often causing them to be fused together. This condition in the eyelids is called "ankyloblepharon filiforme adnatum".

The most common symptoms are intellectual disability and recurrent seizures developing in infancy or early childhood. Typically the seizures are resistant to treatment with anti-epileptic drugs. Other symptoms may include:

- Microcephaly

- Lymphedema

- Facial abnormalities

- Immune deficiencies

- Abnormalities of retina

- Slow growth

- Short stature

Infants with Emanuel syndrome have weak muscle tone (hypotonia) and fail to gain weight and grow at the expected rate (failure to thrive). Their development is significantly delayed, and most affected individuals have severe to profound intellectual disability. Other features of Emanuel syndrome include an unusually small head (microcephaly), distinctive facial features, and a small lower jaw (micrognathia). Ear abnormalities are common, including small holes in the skin just in front of the ears (preauricular pits or sinuses). About half of all affected infants are born with an opening in the roof of the mouth (cleft palate) or a high arched palate. Males with Emanuel syndrome often have genital abnormalities. Additional signs of this condition can include heart defects and absent or unusually small (hypoplastic) kidneys; these problems can be life-threatening in infancy or childhood.

Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome that is usually lethal in the neonatal period. Fryns (1987) reviewed the syndrome.

The Wassel classification is used to categorise radial polydactyly, based upon the most proximal level of skeletal duplication.

X-linked type I Opitz G/BBB Syndrome is diagnosed on clinical findings, but those findings can vary greatly: even within the same family. Manifestations of X-linked type I are classified in the frequent/major findings and minor findings that are found in less than 50% of individuals.

The three major findings that suggest a person has X-linked Type I Opitz G/BBB Syndrome:

1. Ocular hypertelorism (~100% cases)

2. Hypospadias (85-90% cases)

3. Laryngotracheoesophageal abnormalities (60-70%)

Minor findings found in less than 50% of individuals:

1. Developmental delay (especially intellectually)

2. Cleft lip/palate

3. Congenital heart defects

4. Imperforate (blocked) anus

5. Brain defects (especially corpus callosum)

In 1989, Hogdall used ultrasonographs to diagnose X-linked Type I Opitz G/BBB Syndrome after 19 weeks of pregnancy, by identifying hypertelorism (widely-spaced eyes) and hypospadias (irregular urinary tract openings in the penis).

There is also molecular genetic testing available to identify mutations leading to Opitz G/BBB Syndrome. X-linked Type I testing must be done on MID1, since this is the only gene that is known to cause Type I Opitz G/BBB Syndrome. Two different tests can be performed: sequence analysis and deletion/duplication analysis. In the sequence analysis a positive result would detect 15-50% of the DNA sequence mutated, while a deletion/duplication positive result would find deletion or duplication of one or more exons of the entire MID1 gene.

There are several classifications for cleft hand, but the most used classification is described by Manske and Halikis see table 3. This classification is based on the first web space. The first web space is the space between the thumb and the index.

Table 3: Classification for cleft hand described by Manske and Halikis

In humans, a single transverse palmar crease is a single crease that extends across the palm of the hand, formed by the fusion of the two palmar creases (known in palmistry as the "heart line" and the "head line") and is found in people with Down Syndrome. It is also found in 1.5% of the general population in at least one hand.

Because it resembles the usual condition of non-human simians, it is also known as a simian crease or simian line, although these terms have widely fallen out of favor due to their pejorative connotation.

The most frequent reported symptoms in patients with duplication of 22q11.2 duplication syndrome are mental retardation/learning disabilility (97% of patients), delayed psychomotor development (67% of patients), growth retardation (63% of patients) and muscular hypotonia (43% of patients). However, these are common and relatively non-specific indications for cytogenetic analysis, and the extent to which the duplication of 22q11.2 causes these features is currently unknown. The duplication is frequently inherited from a normal parent, so it is clear that intellectual development can be normal.

8p23.1 duplication syndrome is a rare genetic disorder caused by a duplication of a region from human chromosome 8. This duplication syndrome has an estimated prevalence of 1 in 64,000 births and is the reciprocal of the 8p23.1 deletion syndrome. The 8p23.1 duplication is associated with a variable phenotype including one or more of speech delay, developmental delay, mild dysmorphism, with prominent forehead and arched eyebrows, and congenital heart disease (CHD).

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