Typically not diagnosed until late childhood or later, Bonnet–Dechaume–Blanc syndrome usually presents itself with a combination of central nervous system features (midbrain), ophthalmic features (retina), and facial features. The degree of expression of the syndrome's components varies both clinically and structurally. Common symptoms that lead to diagnosis are headaches, retro-orbital pain and hemianopia.

The ophthalmic features of the Bonnet–Dechaume–Blanc syndrome occur as retinal arteriovenous malformation (AVMs). There are three categories of AVMs that are categorized depending on the severity of the malformation. The first category consists of the patient having small lesions that usually are asymptomatic. The second category, more severe than the first, is when the patient’s malformation is missing a connecting capillary. The missing capillary is meant to serve as a link between an artery and a vein; without it, edemas, hemorrhages, and visual impairments can result. Category three, the most severe, occurs when the patient’s malformations are so severe that the dilated vessels cause no distinction between artery and vein. When the symptoms are this severe, the patient has a significantly increased risk of developing vision loss. Since the retinal lesions categorized vary from large vascular malformations that affect a majority of the retina to malformations that are barely visible, the lesions cause a wide range of symptoms including decrease in visual sharpness, proptosis, pupillary defects, optic degeneration and visual field defects. The most common type of visual field impairment due to AVMs is homonymous hemianopia. Homonymous hemianopia typically presents unilaterally, but bilateral cases have been reported as well.

The extent of the central nervous system (CNS) features/symptoms of Bonnet–Dechaume–Blanc syndrome is highly dependent of the location of the cerebral AVMs and the extent of the malformation. The most common symptom affecting the CNS is an intracranial hemangioma in the midbrain. Along with hemangiomas, the malformations result in severe headaches, cerebral hemorrhages, vomiting, meningism, seizures, acute strokes or progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.

The distinguishable facial features that result from Bonnet–Dechaume–Blanc syndrome vary from case to case. A person showing signs of the syndrome may display faint skin discoloration, nevi and angiomas of the skin. Some patients with this disorder also present with high flow arteriovenous malformations of the maxillofacial or mandibular (jaw) regions. Another facial indicator of this disease is malformations affecting the frontal and/or maxillary sinuses.

Bonnet–Dechaume–Blanc syndrome, also known as Wyburn-Mason syndrome, is a rare congential arteriovenous malformation of the brain, retina or facial nevi. The syndrome has a number of possible symptoms and can affect the skin, bones, kidneys, muscles, and gastrointestinal tract. When the syndrome affects the brain, people can experience severe headaches, seizures, acute stroke, meningism and progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.

As for the retina, the syndrome causes retinocephalic vascular malformations that tend to be present with intracranial hemorrhage and lead to decreased visual acuity, proptosis, pupillary defects, optic atrophy, congestion of bulbar conjunctiva, and visual field defects. Retinal lesions can be unilateral and tortuous, and symptoms begin to appear in the second and third decades of life.

The syndrome can present cutaneous lesions, or skin with different texture, thickness, and color, usually on the face. The facial features caused by the syndrome vary from slight discoloration to extensive nevi and angiomas of the skin. In some cases, the frontal and maxillary sinus can present problems in the subject due to the syndrome.

There have only been 52 reported cases of patients with Bonnet–Dechaume–Blanc syndrome as of 2012. Symptoms are rarely noticed in children and the syndrome is often diagnosed in late childhood or early adulthood when visual impairment is noticed. Fluorescein angiography is commonly used to diagnose the syndrome.

There have been several methods in treating patients who display Bonnet–Dechaume–Blanc syndrome. However, which method seems to work the most is within argument. Patients with intracranial lesions have been treated with surgical intervention and in some cases, this procedure has been successful. Other treatments include embolization, radiation therapy, and continued observation.

With limited research on Bonnet–Dechaume–Blanc syndrome, researchers have focused on the clinical and radiological findings rather than how to manage this rare and non-heritable syndrome.

Different people are affected very differently by this disease. The main manifestation is fluid-filled cysts that grow on the brain and can cause damage that varies depending on their location and severity. Symptoms may manifest early in infancy, or may manifest as late as adulthood. Symptoms associated with autosomal dominant porencephaly type I include migraines, hemiplegia or hemiparesis, seizures, cognitive impairment, strokes, dystonia, speech disorders, involuntary muscle spasms, visual field defects, and hydrocephalus.

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.

Patients typically present with low frequency hearing loss detectable via an audiogram. Headaches are frequently present in addition to roaring tinnitus and often some degree of paranoia. Partial vision loss is often present and caused by branch retinal artery occlusions. The presence of refractile or non-refractile yellow Gass plaques in the retinal arterioles is near pathognomonic for the disease. Fluorescein angiography may demonstrate leakage in areas remote from the retinal infarctions.

Susac's syndrome (retinocochleocerebral vasculopathy) is a very rare form of microangiopathy characterized by encephalopathy, branch retinal artery occlusions and hearing loss. The cause is unknown but the current thinking is that antibodies are produced against endothelial cells in tiny arteries which leads to damage and the symptoms related to the illness. Despite this being an extremely rare disease, there are 4 registries collecting data on the illness; two are in the United States, one is in Germany and the fourth is in Portugal.

Among the signs and symptoms demonstrated, by this condition are the following:

- Arachnodactyly

- Congenital diaphragmatic hernia

- Mental dysfunction

- Keratoconus

- Aortic regurgitation

- Blepharophimosis

Autosomal dominant porencephaly type I is a rare type of porencephaly that causes cysts to grow on the brain and damage to small blood vessels, which can lead to cognitive impairment, migraines, seizures, and hemiplegia or hemiparesis.

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

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 primary vitreous used in formation of the eye during fetal development remains in the eye upon birth and is hazy and scarred. The symptoms are leukocoria, strabismus, nystagmus and blurred vision, blindness.

Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy (AD-RVCL) (previously known also as Cerebroretinal Vasculopathy, CRV, or Hereditary Vascular Retinopathy, HVR or Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke, HERNS) is an inherited condition resulting from a frameshift mutation to the TREX1 gene. This genetically inherited condition affects the retina and the white matter of the central nervous system, resulting in vision loss, lacunar strokes and ultimately dementia. Symptoms commonly begin in the early to mid-forties, and treatments currently aim to manage or alleviate the symptoms rather than treating the underlying cause. The overall prognosis is poor, and death can sometimes occur within 10 years of the first symptoms appearing.

AD-RVCL (CRV) Acronym

Autosomal Dominance (genetics) means only one copy of the gene is necessary for the symptoms to manifest themselves.

Retinal Vasculopathy means a disorder that is associated with a disease of the blood vessels in the retina.

Cerebral means having to do with the brain.

Leukodystrophy means a degeneration of the white matter of the brain.

Pathogenesis

The main pathologic process centers on small blood vessels that prematurely “drop out” and disappear. The retina of the eye and white matter of the brain are the most sensitive to this pathologic process. Over a five to ten-year period, this vasculopathy (blood vessel pathology) results in vision loss and destructive brain lesions with neurologic deficits and death.

Most recently, AD-RVCL (CRV) has been renamed. The new name is CHARIOT which stands for Cerebral Hereditary Angiopathy with vascular Retinopathy and Impaired Organ function caused by TREX1 mutations.

Treatment

Currently, there is no therapy to prevent the blood vessel deterioration.

About TREX1

The official name of the TREX1 gene is “three prime repair exonuclease 1.” The normal function of the TREX1 gene is to provide instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during genetic material in preparation for cell division, DNA repair, cell death, and other processes.

Changes (mutations) to the TREX1 gene can result in a range of conditions one of which is AD-RVCL. The mutations to the TREX1 gene are believed to prevent the production of the 3-prime repair exonuclease 1 enzyme. Researchers suggest that the absence of this enzyme may result in an accumulation of unneeded DNA and RNA in cells. These DNA and RNA molecules may be mistaken by cells for those of viral invaders, triggering immune system reactions that result in the symptoms of AD-RVCL.

Mutations in the TREX1 gene have also been identified in people with other disorders involving the immune system. These disorders include a chronic inflammatory disease called systemic lupus erythematosus (SLE), including a rare form of SLE called chilblain lupus that mainly affects the skin.

The TREX1 gene is located on chromosome 3: base pairs 48,465,519 to 48,467,644

The immune system.

- The immune system is composed of white blood cells or leukocytes.

- There are 5 different types of leukocytes.

- Combined, the 5 different leukocytes represent the 2 types of immune systems (The general or innate immune system and the adaptive or acquired immune system).

- The adaptive immune system is composed of two types of cells (B-cells which release antibodies and T-cells which destroy abnormal and cancerous cells).

How the immune system becomes part of the condition.

During mitosis, tiny fragments of “scrap” single strand DNA naturally occur inside the cell. Enzymes find and destroy the “scrap” DNA. The TREX1 gene provides the information necessary to create the enzyme that destroys this single strand “scrap” DNA. A mutation in the TREX1 gene causes the enzyme that would destroy the single strand DNA to be less than completely effective. The less than completely effective nature of the enzyme allows “scrap” single strand DNA to build up in the cell. The buildup of “scrap” single strand DNA alerts the immune system that the cell is abnormal.

The abnormality of the cells with the high concentration of “scrap” DNA triggers a T-cell response and the abnormal cells are destroyed. Because the TREX1 gene is identical in all of the cells in the body the ineffective enzyme allows the accumulation of “scrap” single strand DNA in all of the cells in the body. Eventually, the immune system has destroyed enough of the cells in the walls of the blood vessels that the capillaries burst open. The capillary bursting happens throughout the body but is most recognizable when it happens in the eyes and brain because these are the two places where capillary bursting has the most pronounced effect.

Characteristics of AD-RVCL

- No recognizable symptoms until after age 40.

- No environmental toxins have been found to be attributable to the condition.

- The condition is primarily localized to the brain and eyes.

- Optically correctable, but continuous, deterioration of visual acuity due to extensive multifocal microvascular abnormalities and retinal neovascularization leading, ultimately, to a loss of vision.

- Elevated levels of alkaline phosphatase.

- Subtle vascular changes in the retina resembling telangiectasia (spider veins) in the parafovea circulation.

- Bilateral capillary occlusions involving the perifovea vessels as well as other isolated foci of occlusion in the posterior pole of the retina.

- Headaches due to papilledema.

- Mental confusion, loss of cognitive function, loss of memory, slowing of speech and hemiparesis due to “firm masses” and white, granular, firm lesions in the brain.

- Jacksonian seizures and grand mal seizure disorder.

- Progressive neurologic deterioration unresponsive to systemic corticosteroid therapy.

- Discrete, often confluent, foci of coagulation necrosis in the cerebral white matter with intermittent findings of fine calcium deposition within the necrotic foci.

- Vasculopathic changes involving both arteries and veins of medium and small caliber present in the cerebral white matter.

- Fibroid necrosis of vessel walls with extravasation of fibrinoid material into adjacent parenchyma present in both necrotic and non-necrotic tissue.

- Obliterative fibrosis in all the layers of many vessel walls.

- Parivascular, adventitial fibrosis with limited intimal thickening.

Conditions with similar symptoms that AD-RVCL can be misdiagnosed as:

- Brain tumors

- Diabetes

- Macular degeneration

- Telangiectasia (Spider veins)

- Hemiparesis (Stroke)

- Glaucoma

- Hypertension (high blood pressure)

- Systemic Lupus Erythematosus (SLE (same original pathogenic gene, but definitely a different disease because of a different mutation in TREX1))

- Polyarteritis nodosa

- Granulomatosis with polyangiitis

- Behçet's disease

- Lymphomatoid granulomatosis

- Vasculitis

Clinical Associations

- Raynaud's phenomenon

- Anemia

- Hypertension

- Normocytic anemia

- Normochromic anemia

- Gastrointestinal bleeding or telangiectasias

- Elevated alkaline phosphatase

Definitions

- Coagulation necrosis

- Endothelium

- Fibrinoid

- Fibrinoid necrosis

- Frameshift mutation

- Hemiparesis

- Jacksonian seizure

- Necrotic

- Necrosis

- Papilledema

- Perivascular

- Retinopathy

- Telangiectasia

- Vasculopathy

- Vascular

What AD-RVCL is not:

- Infection

- Cancer

- Diabetes

- Glaucoma

- Hypertension

- A neurological disorder

- Muscular dystrophy

- Systemic Lupus Erythematosis (SLE)

- Vasculitis

Things that have been tried but turned out to be ineffective or even make things worse:

- Antibiotics

- Steroids

- X-Ray therapy

- Immunosuppression

History of AD-RVCL (CRV)

- 1985 – 1988: CRV (Cerebral Retinal Vasculopathy) was discovered by John P. Atkinson, MD at Washington University School of Medicine in St. Louis, MO

- 1988: 10 families worldwide were identified as having CRV

- 1991: Related disease reported, HERNS (Hereditary Endiotheliopathy with Retinopathy, Nephropathy and Stroke – UCLA

- 1998: Related disease reported, HRV (Hereditary Retinal Vasculopathy) – Leiden University, Netherlands

- 2001: Localized to Chromosome 3.

- 2007: The specific genetic defect in all of these families was discovered in a single gene called TREX1

- 2008: Name changed to AD-RVCL Autosomal Dominant-Retinal Vasculopathy with Cerebral Leukodystrophy

- 2009: Testing for the disease available to persons 21 and older

- 2011: 20 families worldwide were identified as having CRV

- 2012: Obtained mouse models for further research and to test therapeutic agents

The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome. Early onset partial aniridia, cerebellar ataxia, and mental retardation are hallmark of syndrome. The iris abnormality is specific and seems pathognomonic of Gillespie syndrome. The aniridia consisting of a superior coloboma and inferior iris hypoplasia, foveomacular dysplasia.

Atypical Gillespie syndrome associated with bilateral ptosis, exotropia, correctopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation.

Neurological signs ar nystagmus, mild craniofacial asymmetry, axial hypotonia, developmental delay, and mild mental retardation. Mariën P did not support the prevailing view of a global mental retardation as a cardinal feature of Gillespie syndrome but primarily reflect cerebellar induced neurobehavioral dysfunctions following disruption of the cerebrocerebellar anatomical circuitry that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS).

Congenital pulmonary stenosis and helix dysplasia can be associated.

Arterial tortuosity syndrome is a rare congenital connective tissue condition disorder characterized by elongation and generalized tortuosity of the major arteries including the aorta. It is associated with hyperextensible skin and hypermobility of joints, however symptoms vary depending on the person. Because ATS is so rare, not much is known about the disease.

Familial exudative vitreoretinopathy (FEVR) ( ) is a genetic disorder affecting the growth and development of blood vessels in the retina of the eye. This disease can lead to visual impairment and sometimes complete blindness in one or both eyes. FEVR is characterized by exudative leakage and hemorrhage of the blood vessels in the retina, along with incomplete vascularization of the peripheral retina. The disease process can lead to retinal folds, tears, and detachments.

The term congenital refers to a condition present from birth (not acquired) and amaurosis refers to a loss of vision "not" associated with a lesion. However, beyond these general descriptions, the presentation of LCA can vary, because it is associated with multiple genes.

LCA is typically characterized by nystagmus, sluggish or absent pupillary responses, and severe vision loss or blindness.

FEVR is, as its name suggests,

familial and can be inherited in an

autosomal dominant, autosomal

recessive or X-linked recessive pattern.1-3 It is caused by mutations in

FZD4, LRP5, TSPAN12 and NDP

genes, which impact the wingless/

integrated (Wnt) receptor signaling

pathway. 3 Disruption of this path

way leads to abnormalities of vascu-

lar growth in the peripheral retina. 2,3

It is typically bilateral, but asymmetric, with varying degrees of

progression over the individual’s

lifetime. Age of onset varies, and

visual outcome can be strongly

influenced by this factor. Patients

with onset before age three have a

more guarded long-term prognosis

whereas those with later onset are

more likely to have asymmetric

presentation with deterioration of

vision in one eye only. 2-3 However,

because FEVR is a lifelong disease,

these patients are at risk even as

adults.2 Ocular findings and useful

vision typically remain stable if the

patient does not have deterioration

before age 20.2,4 Due to the variability and unpredictability of the

disease course, patients with FEVR

should be followed throughout

their lifetime.

Clinical presentation can vary

greatly. In mild variations, patients

may experience peripheral vascular

changes, such as peripheral avascular zone, vitreoretinal adhesions,

arteriovenous anastomoses and a

V-shaped area of retinochoroidal

degeneration. 4 Severe forms may

present with neovascularization,

subretinal and intraretinal hemorrhages and exudation. 4 Neovascularization is a poor prognostic

indicator and can lead to retinal

folds, macular ectopia and tractional retinal detachment. 2,4 Widefield FA has been crucial in

helping to understand this disease,

as well as helping to confirm the

diagnosis. An abrupt cessation

of the retinal capillary network

in a scalloped edge posterior to

fibrovascular proliferations can

be made using FA.2,3,5 Patients can

also show delayed transit filling on

FA as well as delayed/patchy choroidal filling, bulbous vascular terminals, capillary dropout, venous/venous shunting and abnormal

branching patterns. 2,3,5 The staging of FEVR is similar

to that of retinopathy of prematurity. The first two stages involve an

avascular retinal periphery with or

without extraretinal vascularization (stage 1 and 2, respectively). 4 Stages three through five delineate

levels of retinal detachment; stage 3

is subtotal without foveal involvement, stage 4 is subtotal with foveal

involvement and stage 5 is a total

detachment, open or closed funnel.4

Because there was neovascularization in the absence of retinal detachment, our patient was

considered to have

stage 2.

Clinical manifestations of intraparenchymal hemorrhage are determined by the size and location of hemorrhage, but may include the following:

- Hypertension, fever, or cardiac arrhythmias

- Nuchal rigidity

- Subhyaloid retinal hemorrhages

- Altered level of consciousness

- Anisocoria, Nystagmus

- Focal neurological deficits

- Putamen - Contralateral hemiparesis, contralateral sensory loss, contralateral conjugate gaze paresis, homonymous hemianopsia, aphasia, neglect, or apraxia

- Thalamus - Contralateral sensory loss, contralateral hemiparesis, gaze paresis, homonymous hemianopia, miosis, aphasia, or confusion

- Lobar - Contralateral hemiparesis or sensory loss, contralateral conjugate gaze paresis, homonymous hemianopia, abulia, aphasia, neglect, or apraxia

- Caudate nucleus - Contralateral hemiparesis, contralateral conjugate gaze paresis, or confusion

- Brain stem - Tetraparesis, facial weakness, decreased level of consciousness, gaze paresis, ocular bobbing, miosis, or autonomic instability

- Cerebellum - Ataxia, usually beginning in the trunk, ipsilateral facial weakness, ipsilateral sensory loss, gaze paresis, skew deviation, miosis, or decreased level of consciousness

Gillespie syndrome, also called aniridia, cerebellar ataxia and mental deficiency. is a rare genetic disorder. The disorder is characterized by partial aniridia (meaning that part of the iris is missing), ataxia (motor and coordination problems), and, in most cases, intellectual disability. It is heterogeneous, inherited in either an autosomal dominant or autosomal recessive manner. Gillespie syndrome was first described by American ophthalmologist Fredrick Gillespie in 1965.

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.

Leber's congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life.

One form of LCA was successfully treated with gene therapy in 2008.

It affects about 1 in 40,000 newborns. LCA was first described by Theodor Leber in the 19th century. It should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodor Leber.

Note: *faciobrachial deficits greater than that of the lower limb

It causes facial abnormalities, skeletal malformation and occasionally neural tube defects; the skeletal disfigurements resolve to a degree in the course of development.

Mutations in different parts of the gene may lead to deafness or Stickler syndrome type III (eye problems: myopia, retinal detachment and skeletal abnormalities).

Infants and children: Infants that are born with Weissenbacher-Zweymüller syndrome usually have short bones in their arms and legs. The thigh and upper arm bones are wider than usual resulting in a dumbbell-shape while the bones of the vertebrae may be abnormal. Typical abnormal facial features can be wide-set protruding eyes (hypertelorism), a small and upturned nose with a flat bridge, small jaw (micrognathia) and a cleft palate. Some infants have high-frequency hearing loss. Infants may also exhibit a psychomotor delay. After the period of growth deficiency the individual makes improvements in bone growth leading to a normal physical development around age 5 or 6.

Adults: Many with Weissenbacher-Zweymüller syndrome have a catch-up growth phase causing the adults to not be unusually short. Many adults still will have hearing loss and typical abnormal facial features of Weissenbacher-Zweymüller syndrome.

Retinal lesions, called astrocytic hamartomas (or "phakomas"), which appear as a greyish or yellowish-white lesion in the back of the globe on the ophthalmic examination. Astrocytic hamartomas can calcify, and they are in the differential diagnosis of a calcified globe mass on a CT scan.

Nonretinal lesions associated with TSC include:

- Coloboma

- Angiofibromas of the eyelids

- Papilledema (related to hydrocephalus)

The specific and familial association of BIFE and PKC defines a novel clinical entity : the infantile convulsions and choreoathetosis syndrome. The first observation was made in four families where children were affected with nonfebrile convulsions at age 3–12 months.Partial epileptic seizures started with a psychomotor arrest and a deviation of the head and eyes to one side, followed inconstantly by unilateral jerks.In some cases, seizures generalized secondarily. None of the interictal electroencephalograms showed epileptiform abnormalities, and magnetic-resonance imaging were normal. These convulsions had a favorable outcome. At 5–8 years of age affected children developed abnormal movements. They presented with twisting movements of the hands of a reptilian type when stressed or embarrassed. They also developed jerky movements of the legs after running. Initially, abnormal movements were intermediate in speed between quick and slow, typical of paroxysmal choreoathetosis. Combinations of abnormal movements involving the arms, legs, trunk and occasionally the head were observed. The attacks lasted only a few minutes, occurring with a frequency of 5-30 episodes per day and were not accompanied by unconsciousness. In all patients, abnormal movements disappeared at 25–30 years of age without any treatment. Since the first report similar clinical presentations have been published which confirm the specificity of the ICCA syndrome.