Chief markers of Goldenhar syndrome are incomplete development of the ear, nose, soft palate, lip, and mandible on usually one side of the body. Additionally, some patients will have growing issues with internal organs, especially heart, kidneys, and lungs. Typically, the organ will either not be present on one side or will be underdeveloped. Note that while it is more usual for there to be problems on only one side, it has been known for defects to occur bilaterally (approximate incidence 10% of confirmed GS cases).

Other problems can include severe scoliosis (twisting of the vertebrae), limbal dermoids, and hearing loss (see hearing loss with craniofacial syndromes), and deafness or blindness in one or both ears/eyes, Granulosa cell tumors may be associated as well.

Lisch epithelial corneal dystrophy (LECD), also known as band-shaped and whorled microcystic dystrophy of the corneal epithelium, is a rare form of corneal dystrophy first described in 1992 by Lisch et al. In one study it was linked to chromosomal region Xp22.3, with as yet unknown candidate genes.

The main features of this disease are bilateral or unilateral gray band-shaped and feathery opacities. They sometimes take on a form of a whirlpool, repeating the known pattern of corneal epithelium renewal. Abrasion of the epithelium in 3 patients brought only temporary relief, with abnormal epithelium regrowth in several months.

Epithelial cells in the zones of opacity were shown to have diffuse cytoplasmic vacuoles with as yet unestablished content.

Goldenhar syndrome (also known as oculo-auriculo-vertebral (OAV) syndrome) is a rare congenital defect characterized by incomplete development of the ear, nose, soft palate, lip, and mandible. It is associated with anomalous development of the first branchial arch and second branchial arch. Common clinical manifestations include limbal dermoids, preauricular skin tags, and strabismus.

The term is sometimes used interchangeably with hemifacial microsomia, although this definition is usually reserved for cases without internal organ and vertebrae disruption.

It affects between 1/3,500 and 1/26,000 live births, with a male:female ratio of 3:2.

Keratitis–ichthyosis–deafness syndrome (also known as "Erythrokeratodermia progressiva Burns," "Ichthyosiform erythroderma, corneal involvement, and deafness," and "KID syndrome,") presents at birth/infancy and is characterized by pregressive corneal opacification, either mild generalized hyperkeratosis or discrete erythematous plaques, and neurosensory deafness.

It is caused by a mutation in connexin 26.

Congenital hereditary corneal dystrophy (CHED) is a form of corneal dystrophy which presents at birth.

The age of onset is in a child's infancy. Bilateral corneal opacification started in the second year of life and led to severe visual impairment. However, cornea surgery and replacement resulted in better vision.

Symptoms include a combination of spinocerebellar degeneration and corneal dystrophy. Mental retardation and slowly progressive cerebellar abnormalities were also diagnosed in patients. Other symptoms include corneal edema, thickening of Descemet membrane, and degenerative pannus. Abnormalities were found in muscle and sural nerves.

In the recessive form corneal clouding is observed at birth or within the neonatal period, nystagmus is often present, but no photophobia or epiphora is seen. In the autosomal dominant type corneal opacification is usually seen in the first or second year of life and progresses slowly, and nystagmus is infrequently seen.

Onset occurs in the first decade, usually between ages 5 and 9. The disorder is progressive. Minute, gray, punctate opacities develop. Corneal sensitivity is usually reduced. Painful attacks with photophobia, foreign body sensations, and recurrent erosions occur in most patients. Macular corneal dystrophy is very common in Iceland and accounts for almost one-third of all corneal grafts performed there.

Corneal-cerebellar syndrome (also known as Der Kaloustian-Jarudi-Khoury syndrome) is an autosomally resessive disease that was first described in 1985. Three cases are known: all are sisters in the same family.

X-linked endothelial corneal dystrophy (XECD) is a rare form of corneal dystrophy described first in 2006, based on a 4-generation family of 60 members with 9 affected males and 35 trait carriers, which led to mapping the XECD locus to Xq25. It manifests as severe corneal opacification or clouding, sometimes congenital, in the form of a ground glass, milky corneal tissue, and moon crater-like changes of corneal endothelium. Trait carriers manifest only endothelial alterations resembling moon craters.

As of December 2014, the molecular basis for this disease remained unknown, although 181 genes were known to be within the XECD locus, of which 68 were known to be protein-coding.

Anterior segment mesenchymal dysgenesis is a failure of the normal development of the tissues of the anterior segment of the eye. It leads to anomalies in the structure of the mature anterior segment, associated with an increased risk of glaucoma and corneal opacity.

Peters' (frequently misspelled Peter's) anomaly is a specific type of mesenchymal anterior segment dysgenesis, in which there is central corneal leukoma, adhesions of the iris and cornea, and abnormalities of the posterior corneal stroma, Descemet's membrane, corneal endothelium, lens, and anterior chamber.

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.

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

Thiel–Behnke dystrophy, or Corneal dystrophy of Bowman layer, type II, is a rare form of corneal dystrophy affecting the layer that supports corneal epithelium.

The dystrophy was first described in 1967 and initially suspected to denote the same entity as the earlier-described Reis-Bucklers dystrophy, but following a study in 1995 by Kuchle et al. the two look-alike dystrophies were deemed separate disorders.

Subepithelial mucinous corneal dystrophy (SMCD) is a rare form of corneal dystrophy. It was first described in 1993 by Feder et al. Anterior to Bowman layer, deposits of glycosaminoglycan were detected and identified as chondroitin-4-sulfate and dermatan sulfate.

Ramos-Arroyo syndrome is marked by corneal anesthesia, absence of the peripapillary choriocapillaris and retinal pigment epithelium, bilateral sensorineural hearing loss, unusual facial appearance, persistent ductus arteriosus, Hirschsprung disease, and moderate intellectual disability. It appears to be a distinct autosomal dominant syndrome with variable expressivity.

As of 2008 this syndrome has only been reported in five individuals within three generations of the same family; two young children, their mother, their uncle and their maternal grandmother. This most recent generation to be diagnosed with Ramos-Arroyo syndrome supports the hypothesis that this disease is a distinct autosomal

dominant disorder. If this syndrome could be identified in other families it may help to discriminate the gene responsible.

Macular corneal dystrophy, also known as Fehr corneal dystrophy named for German ophthalmologist Oskar Fehr (1871-1959), is a rare pathological condition affecting the stroma of cornea. The first signs are usually noticed in the first decade of life, and progress afterwards, with opacities developing in the cornea and attacks of pain. The condition was first described by Arthur Groenouw in 1890.

Sclerocornea is a congenital anomaly of the eye in which the cornea blends with sclera, having no clear-cut boundary. The extent of the resulting opacity varies from peripheral to total ("sclerocornea totalis"). The severe form is thought to be inherited in an autosomal recessive manner, but there may be another, milder form that is expressed in a dominant fashion. In some cases the patients also have abnormalities beyond the eye (systemic), such as limb deformities and craniofacial and genitourinary defects.

According to one tissue analysis performed after corneal transplantation, the sulfation pattern of keratan sulfate proteoglycans in the affected area is typical for corneal rather than scleral tissue.

Sclerocornea may be concurrent with cornea plana.

Spastic ataxia-corneal dystrophy syndrome (also known as Bedouin spastic ataxia syndrome) is an autosomally resessive disease. It has been found in an inbred Bedouin family. It was first described in 1986. A member of the family who was first diagnosed with this disease also had Bartter syndrome. It was concluded by its first descriptors Mousa-Al et al. that the disease is different from a disease known as corneal-cerebellar syndrome that had been found in 1985.

Symptoms include spastic ataxia, cataracts, macular corneal dystrophy and nonaxial myopia. Mental development is normal.

Posterior amorphous corneal dystrophy (PACD) is a rare form of corneal dystrophy. It is not yet linked to any chromosomal locus. The first report describing this dystrophy dates back to 1977.

To clarify whether Thiel–Behnke corneal dystrophy is a separate entity from Reis-Bucklers corneal dystrophy, Kuchle et al. (1995) examined 28 corneal specimens with a clinically suspected diagnosis of corneal dystrophy of the Bowman layer by light and electron microscopy and reviewed the literature and concluded that 2 distinct autosomal dominant corneal dystrophy of Bowman layer (CBD) exist and proposed the designation CDB type I (geographic or 'true' Reis-Bucklers dystrophy) and CDB type II (honeycomb-shaped or Thiel–Behnke dystrophy). Visual loss is significantly greater in CDB I, and recurrences after corneal transplantation seem to be earlier and more extensive in CDB I.

Meesmann corneal dystrophy, also "Stocker-Holt dystrophy", is a type of corneal dystrophy and a keratin disease.

It is named for German ophthalmologist Alois Meesmann (1888-1969).

It is sometimes called "Meesmann-Wilke syndrome", after the joint contribution of Meesmann and Wilke.

Terrien marginal degeneration is a noninflammatory, unilateral or asymmetrically bilateral, slowly progressive thinning of the peripheral corneal stroma.

The cause of Terrien marginal degeneration is unknown, its prevalence is roughly equal between males and females, and it usually occurs in the second or third decade of life.

Schnyder crystalline corneal dystrophy (SCD) is a rare form of corneal dystrophy. It is caused by heterozygous mutations in UBIAD1 gene. Cells in the cornea accumulate cholesterol and phosopholipid deposits leading to the opacity, in severe cases requiring corneal transplants. Abnormal cholesterol metabolism has been noted in other cell types of affected patients (skin fibroblasts) suggesting that this may be a systemic disorder with clinical manifestations limited to the cornea.

The typical infant who has congenital glaucoma usually is initially referred to an ophthalmologist because of apparent corneal edema. The commonly described triad of epiphora (excessive tearing), blepharospasm and photophobia may be missed until the corneal edema becomes apparent.