Causes of the one and a half syndrome include pontine hemorrhage, ischemia, tumors, infective mass lesions such as tuberculomas, and demyelinating conditions like multiple sclerosis.

The syndrome usually results from single unilateral lesion of the paramedian pontine reticular formation and the ipsilateral medial longitudinal fasciculus. An alternative anatomical cause is a lesion of the abducens nucleus (VI) on one side (resulting in a failure of abduction of the ipsilateral eye and adduction of the contralateral eye = conjugate gaze palsy towards affected side), with interruption of the ipsilateral medial longitudinal fasciculus after it has crossed the midline from its site of origin in the contralateral abducens (VI) nucleus (resulting in a failure of adduction of the ipsilateral eye).

The clinical manifestations present at birth are generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. The congenital muscular dystrophy is characterized by hypoglycosylation of α-dystroglycan.

Those born with the disease also experience severe ocular and brain defects. Half of all children with WWS are born with encephalocele, which is a gap in the skull that will not seal. The meninges of the brain protrude through this gap due to the neural tube failing to close during development. A malformation of the a baby's cerebellum is often a sign of this disease.Common ocular issues associated with WWS are abnormally small eyes and retinal abnormalities cause by an underdeveloped light-sensitive area in the back of the eye.

The term "cat eye" syndrome was coined because of the particular appearance of the vertical colobomas in the eyes of some patients. However, over half of the CES patients in the literature do not present with this trait.

Facial features found in this syndrome include

- dolichocephaly

- hypertelorism

- ptosis

- microretrognathia

- high arched palate

- long flat philtrum

- low set ears

Non facial features of this syndrome include

- hyperextensibility

- hypotonia

- lateral meningoceles

The lateral meningocoles are a common finding in this syndrome. They may be associated with neurological abnormalities and result in bladder dysfunction and neuropathy.

Walker–Warburg syndrome (WWS), also called Warburg syndrome, Chemke syndrome, HARD syndrome (Hydrocephalus, Agyria and Retinal Dysplasia), Pagon syndrome, cerebroocular dysgenesis (COD) or cerebroocular dysplasia-muscular dystrophy syndrome (COD-MD), is a rare form of autosomal recessive congenital muscular dystrophy. It is associated with brain (lissencephaly, hydrocephalus, cerebellar malformations) and eye abnormalities. This condition has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years.

The additional chromosome 22 usually arises spontaneously. It may be hereditary and parents may be mosaic for the marker chromosome but show no phenotypic symptoms of the syndrome.

The chromosomal area included in the cat eye syndrome "critical region" is 22pter→q11.

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.

The disorder is caused by injury or dysfunction in the medial longitudinal fasciculus (MLF), a heavily myelinated tract that allows conjugate eye movement by connecting the paramedian pontine reticular formation (PPRF)-abducens nucleus complex of the contralateral side to the oculomotor nucleus of the ipsilateral side.

In young patients with bilateral INO, multiple sclerosis is often the cause. In older patients with one-sided lesions a stroke is a distinct possibility. Other causes are possible.

The lateral meningocele syndrome is a very rare skeletal disorder with facial anomalies, hypotonia and meningocele-related neurologic dysfunction.

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.

PEHO syndrome is a progressive encephalopathy with edema, hypsarrhythmia and optic atrophy. It is a very rare disease, one of the Finnish heritage diseases, although approximately half of the cases reported so far are not-Finnish and have been described worldwide .

It has been suggested that it may also be present in Australian and American populations.

The most common malformation in patients with the syndrome is kidney hypodysplasia, which are small and underdeveloped kidneys, often leading to end-stage renal disease (ESRD). Estimates show approximately 10% of children with hypoplastic kidneys are linked to the disease. Many different histological abnormalities have been noted, including:

- decrease in nephron number associated with hypertrophy

- focal segmental glomerulosclerosis

- interstitial fibrosis and tubular atrophy

- multicystic dysplastic kidney

Up to one-third of diagnosed patients develop end stage kidney disease, which may lead to complete kidney failure.

Internuclear ophthalmoplegia (INO) is a disorder of conjugate lateral gaze in which the affected eye shows impairment of adduction. When an attempt is made to gaze contralaterally (relative to the affected eye), the affected eye adducts minimally, if at all. The contralateral eye abducts, however with nystagmus. Additionally, the divergence of the eyes leads to horizontal diplopia. That is, if the right eye is affected the patient will "see double" when looking to the left, seeing two images side-by-side. Convergence is generally preserved.

Symptoms include:

- opsoclonus (rapid, involuntary, multivectorial (horizontal and vertical), unpredictable, conjugate fast eye movements without intersaccadic [quick rotation of the eyes] intervals)

- myoclonus (brief, involuntary twitching of a muscle or a group of muscles)

- cerebellar ataxia, both truncal and appendicular

- aphasia (a language disorder in which there is an impairment of speech and of comprehension of speech, caused by brain damage)

- mutism (a language disorder in which a person does not speak despite evidence of speech ability in the past, often part of a larger neurological or psychiatric disorder)

- lethargy

- irritability or malaise

- drooling

- strabismus (a condition in which the eyes are not properly aligned with each other)

- vomiting

- sleep disturbances

About half of all OMS cases occur in association with neuroblastoma (a cancer of the sympathetic nervous system usually occurring in infants and children).

Symptoms include:

- intellectual disability (more than half of the patients have an IQ below 50)

- microcephaly

- sometimes pancytopenia (low blood counts)

- cryptorchidism

- low birth weight

- dislocations of pelvis and elbow

- unusually large eyes

- low ears

- small chin

A case was described in 1957 by Michail, Matsoukas and Theodorou. In 1963, Jack Herbert Rubinstein (1925–2006) and Hooshang Taybi (1919–2006) described a larger series of cases.

Typical features of the disorder include:

- Broad thumbs and broad first toes and clinodactyly of the 5th finger

- Mental disability

- Small height, low bone growth, small head

- Cryptorchidism in males

- Unusual facies involving the eyes, nose, and palate

- Anesthesia may be dangerous in these patients: "According to the medical literature, in some cases, individuals with Rubinstein–Taybi syndrome may have complications (e.g., respiratory distress and/or irregular heart beats [cardiac arrythmias]) associated with a certain muscle relaxant (succinylcholine) and certain anesthesia. Any situations requiring the administration of anesthesia or succinylcholine (e.g., surgical procedures) should be closely monitored by skilled professionals (Anesthesiologists)." Primary literature suggests the children may have a higher rate of cardiac physical and conduction abnormalities which may cause unexpected results with cardioactive medications. A further editorial reply in the British Journal of Anaesthesia discusses changes in the face and airway structure making it more difficult to secure the airway under anaesthesia, however, complications appeared in a minority of cases, and routine methods of airway control in the operating room appears to be successful. They recommended close individual evaluation of Rubinstein–Taybi patients for anaesthetic plans.

A 2009 study found that children with RTS were more likely to be overweight and to have a short attention span, motor stereotypies, and poor coordination, and hypothesized that the identified CREBBP gene impaired motor skills learning. Other research has shown a link with long-term memory (LTM) deficit. See also Epigenetics in learning and memory.

Ocular disc dysplasia is the most notable ocular defect of the disease. An abnormal development in the optic stalk causes optic disc dysplasia, which is caused by a mutation in the "Pax2" gene. The nerve head typically resembles the morning glory disc anomaly, but has also been described as a coloboma. A coloboma is the failure to close the choroid fissure, which is the opening from the ventral side of the retina in the optic stalk. Despite the similarities with coloboma and morning glory anomaly, significant differences exist such that optic disc dysplasia cannot be classified as either one entity.

Optic disc dysplasia is noted by an ill-defined inferior excavation, convoluted origin of the superior retinal vessels, excessive number of vessels, infrapapillary pigmentary disturbance, and slight band of retinal elevation adjacent to the disk. Some patients have normal or near normal vision, but others have visual impairment associated with the disease, though it is not certain if this is due only to the dysplastic optic nerves, or a possible contribution from macular and retinal malformations. The retinal vessels are abnormal or absent, in some cases having small vessels exiting the periphery of the disc. There is a great deal of clinical variability.

The ‘Harlequin Sign’ is unilateral flushing and sweating of the face, neck, and upper chest usually after exposure to heat or strenuous exertion. Horner syndrome, another problem associated with the sympathetic nervous system, is often seen in conjunction with harlequin syndrome.

Since Harlequin syndrome is associated with a dysfunction in the autonomic nervous system, main symptoms of this dysfunction are in the following: Absence of sweat(anhidrosis) and flushing on one side of the face, neck, or upper thoracic area. In addition, other symptoms include cluster headaches, tearing of the eyes, nasal discharge, abnormal contraction of the pupils, weakness in neck muscles, and drooping of on side of the upper eyelid.

The acronym CHILD stands for the symptoms of the syndrome:

- CH = Congenital Hemidysplasia—One side of the body, most of the time the right side, is poorly developed. The right ribs, neck, vertebrae, etc. may be underdeveloped and the internal organs may be affected.

- I - Ichthyosiform Erythroderma—At birth or shortly after birth, there are red, inflamed patches (erythroderma), and flaky scales (ichthyosis) on the side of the body that is affected. Hair loss on the same side may also be possible.

- LD - limb defects—Fingers on the hand or toes on the foot of the affected side may be missing. An arm or leg may also be shortened or even missing.

One possible cause of Harlequin syndrome is a lesion to the preganglionic or postganglionic cervical sympathetic fibers and parasympathetic neurons of the ciliary ganglion. It is also believed that torsion (twisting) of the thoracic spine can cause blockage of the anterior radicular artery leading to Harlequin syndrome. The sympathetic deficit on the denervated side causes the flushing of the opposite side to appear more pronounced. It is unclear whether or not the response of the undamaged side was normal or excessive, but it is believed that it could be a result of the body attempting to compensate for the damaged side and maintain homeostasis.

Since the cause and mechanism of Harlequin syndrome is still unknown, there is no way to prevent this syndrome.

Rubinstein–Taybi syndrome (RTS), also known as broad thumb-hallux syndrome or Rubinstein syndrome, is a condition characterized by short stature, moderate to severe learning difficulties, distinctive facial features, and broad thumbs and first toes. Other features of the disorder vary among affected individuals.

People with this condition have an increased risk of developing noncancerous and cancerous tumors, leukemia, and lymphoma. This condition is sometimes inherited as an autosomal dominant pattern and is uncommon, many times it occurs as a de novo (not inherited) occurrence, it occurs in an estimated 1 in 125,000-300,000 births.

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.

In most cases OMS starts with an acute flare-up of physical symptoms within days or weeks, but some less obvious symptoms such as irritability and malaise may begin weeks or months earlier.

Patients with Sack–Barabas syndrome have thin, fragile skin, especially in the chest and abdomen, that bruises easily; hands and feet may have an aged appearance. Skin is soft but not overly stretchy.

Facial features are often distinctive, including protruding eyes, a thin nose and lips, sunken cheeks, and a small chin.

Other signs of the disorder include hypermobility of joints, tearing of tendons and muscles, painfully swollen veins in the legs, lung collapse, and slow wound healing following injury or surgery.

Infants with the condition may be born with hip dislocations and clubfeet.

Unpredictable ruptures of arteries and organs are serious complications of SBS. Ruptured arteries can cause internal bleeding, stroke, or shock, the most common cause of death in patients with this disorder.

Rupture of the intestine is seen in 25 to 30 percent of affected individuals and tearing of the uterus during pregnancy affects 2 to 3 percent of women. Although these symptoms are rare in childhood, more than 80 percent of patients experience severe complications by the age of 40. Teenage boys are at high risk for arterial rupture, often being fatal.