Aykardi's syndrome

Description:

Aykardi's (Aicardi syndrom) syndrome is the rare genetic disease which is characterized by a corpus collosum agenesia, epileptic attacks as infantile spasms with an early debut, specific lacunary changes on an eyeground, typical changes on EEG (a pattern of "the split brain"), a delay of psychomotor development, and also a front dizmorfizm.

Reasons of a syndrome of Aykardi:

Especially large number in Japan is known approximately of 500 cases of a syndrome of Aykardi around the world. The syndrome occurs at children with various race. On the researches which are recently conducted in Sweden prevalence of a syndrome of Aykardi makes from 2 to 15 cases on 100000 girls. (In Russia similar researches unfortunately were not conducted). However, considering a phenotypical variety and diagnostic difficulties, many cases remain not diagnosed. It allows to revise data on true prevalence of a syndrome of Aykardi towards increase, perhaps, Aykardi's syndrome is more frequent reason of a delay of intellectual development and infantile spasms at girls, than it is considered now. Today it is considered that incidence of a syndrome of Aykardi among all children with infantile spasms makes only about 2-4%.

Mode of inheritance of a syndrome of Aykardi-dominant linked to X-chromosome, to a presumable locus of Hr22.3. Only girls are ill. Three boys to whom the diagnosis was made – Aykardi's syndrome had HHY genotype (47 chromosomes) - Klyaynfelter's syndrome. For a male fruit with XY genotype Aykardi's syndrome is deadly. Except for one couple of sisters all described cases are sporadic. All cases of a syndrome of Aykardi are probably connected with new mutations as any case of transfer from mother to the daughter of the gene linked to X-chromosome, which is responsible for development of Aykardi's syndrome is not registered. Risk of the birth in one family of the second child with a syndrome of Aykardi-less than 1%. Theoretically, the risk of transfer of a mutant allele from the woman with a syndrome of Aykardi-of 50%, however a male fruit, the carrier of a mutant gene is impractical. Thus, among the expected posterity 33%-healthy girls, 33%-healthy boys and 33% - the girl with a syndrome Aykardi.

He and his family worried awful 1811th lean year in Madrid, and this cruel check on endurance became too heavy for his wife Josefa. In June, 1812, she died, and the 66-year-old deaf old man remained one in the house.

The pathogeny of a syndrome of Aykardi is unknown, connected with genetically determined disturbances of a stage of neyronalny migration now.

Symptoms of a syndrome of Aykardi:

Children, as a rule, are born externally healthy, with normal gestational age at the birth, without complications in the prenatal and intranatal period, and develop on age approximately to 2-5 (more often 3) months when most often debut infantile spasms. Infantile spasms are a type of the epileptic attacks representing massive myoclonic and (or) tonic about - and (or) the retropulsivny, symmetric and (or) asymmetric, serial and (or) isolated spasms of axial and konechnostny muscles. In 97% of cases at Aykardi's syndrome fleksorny infantile spasms which can be atypical, lateralizovanny are observed. 42% of patients with Aykardi's syndrome have a combination of infantile spasms to other types of epileptic attacks, is more often with partial, is more rare with generalized toniko-clonic. So, manifest symptoms are infantile spasms or partial attacks are more rare, the debut of epileptic attacks in 68% of observations falls on the first three months of life, in 23% of cases the syndrome debuts neonatal spasms in the first month of life. Convulsive paroxysms of a rezistentna to the carried-out anticonvulsant therapy.

The most part of girls with Aykardi's syndrome has a sharp delay of psychomotor development. But cases of insignificant decrease in intelligence and a moderate arrest of development are described. In the neurologic status it is often noted – a nanocephalia, a hypomyotonia, the unilateral muscular hypertension and spasticity, brisk deep tendon jerks or gemi-or tetraparesis is possible. The corpus collosum agenesia at Aykardi's syndrome usually total, is often combined with a heterotopy of cortical substance of a brain, a bark atrophy, structural asymmetry of parencephalons, normotensive hydrocephaly, a polymicrogyria or a pakhigiriya, choroidal cysts and papillomas, a ventrikulomegaliya, intracerebral cysts, the Dandy Walker's syndrome. It is supposed that existence of a complex of anomalies of neyronalny migration is even more specific to Aykardi's syndrome, than the isolated corpus collosum agenesia.

Anomalies of an organ of sight: at Aykardi's syndrome a big variety of anomaly of development of eyes is described. Patogmonichny for this syndrome is the pigmental retinitis which is shown various extent of decrease in visual acuity (is more often than quite expressed). Other described anomalies of eyes include a microphthalmia, an atrophy of an optic nerve, a coloboma, a cataract which can be one - either bilateral, or asymmetric.

Skeletal anomalies: such inborn defects as semi-vertebras and otsutstvuyushche the edges sometimes leading to the expressed scoliosis at a third of patients are noted.

Maxillofacial anomalies: there are no descriptions of characteristic front symptoms at Aykardi's syndrome but which are most often found according to the authors observing 40 girls with Aykardi's syndrome today speakers cutters, the hitched-up nose tip, the reduced corner of a nasal partition, the located eyebrows (the signs shown at a half of patients) rare lateralno are. The anomalies of a structure of the person described earlier in the isolated cases include front asymmetry, anomalies of a structure of auricles and the flattened nasal partition, a hypertelorism, a ptosis, a hypoplasia of a nose and a micrognatia, a crevice of an upper lip and the sky. Authors also described various skin defeats (including a nevus, skin diverticulums, hemangiomas, angiosarcomas) – at 20% of patients. Malformations of extremities (at 7,5%), included a kaptodaktiliya, a proximal arrangement of a thumb, a hypoplasia of little fingers, asymmetry of extremities, the only cross palmar fold, incomplete doubling of a thumb a syndactylia of 2 and 3 fingers of feet.
Digestive tract: gastroyezofagalny reflux, locks, diarrhea and difficulties with feeding.

At patients with Aykardi's syndrome the frequency of cases of tumors is increased. Most often it is papilloma of vascular textures, the hemangioma, an angiosarcoma, a hepatoblastoma, intestines polyposes, embryonal carcinomas are also described.

Growth. Growth rate is slowed down at the age of 7-10 years and corresponds 5 центилю below, increase in weight is also slowed down to this age to 25 центиля below.

Endocrine system. Perhaps early approach of puberty or delay of sexual development.

Diagnosis:

So far there is no special laboratory diagnostic test or a research which would allow to make the diagnosis of a syndrome of Aykardi. For this purpose it is necessary: neurologic survey, an oftalmoskopiya, EEG, MRT with contrast and/or without, the roentgenogram of a skeleton.

On MRT it is possible to find a corpus collosum agenesia, asymmetry of hemispheres of bark, a heterotopy of cortical substance, intracerebral cysts, papilloma of vascular textures and тд. Bark axons which normal have to cross at its agenesia do not form and respectively are not identified at neurovisualization.

The agenesia of a corpus collosum allows side ventricles to extend up, in frontal and parietal white matter. This state is called as an upper translocation of side ventricles to parietofrontal regions of a brain. Similar shift undergoes also the III ventricle up that is one of neuroradiological markers of an agenesia of a corpus collosum. The increased III ventricle, being pushed forward and up, moves apart front horns of side ventricles, at the accompanying hydrocephaly the volume of ventricles increases, back horns extend and bent towards the average line (a form of "oven fork"). Possibly lack of the supporting function of a corpus collosum is a basis for typical line of an agenesia of a corpus collosum - expansions of hemispheres, the III ventricle and Monroyev of an opening.

Typical changes on EEG in the form of a hypsarrhythmia, characteristic of infantile spasms occur not at all patients. The most characteristic changes of criminal EEG consist in flashes of irregular bystry and slow waves lasting from 3 up to 6 seconds which alternate some flattening of the main rhythm within 5-20 seconds, and changes are not synchronized on hemispheres. On EEG – a phenomenon of "the split brain" ("Split-brain"). As practically at a half (42%) of patients infantile spasms are combined with other types of epileptic attacks, data of EEG can be contradictory.

At an oftalmoskopiya well delimited, round depigmented sites are found white, or ochroleucous color.

Prenatal diagnosis:

The prenatal molecular and genetic research (DNA diagnosis) – meanwhile is impossible as the gene is definitely not revealed. Nevertheless, even without DNA analysis at Aykardi's syndrome prenatal diagnosis by means of ultrasonography is possible. Applying a technique of ultrasonic scanning of a fruit in the pre-natal period on early terms of gestational development it is possible to reveal a corpus collosum agenesia. It is also possible to reveal some other anomalies, such as intracerebral cysts. Thus, ultrasonic and, perhaps, other neurovisualization methods which are actively developed in recent years (such as fruit MRT) are able to afford to suspect Aykardi's syndrome of the prenatal period.

The forecast at Aykardi's syndrome is, as a rule, serious in connection with the expressed mental retardation and the resistant nature of spasms. A part of children (to 25%) perishes in the first years of life. From the survived children only 25% independently go and only 50% have skills of self-service. Life expectancy is very variable, depending on degree of manifestation of symptoms. Average life expectancy according to different data makes from 8,3 to 18,5 years. But there is information about the woman of 32 years with a syndrome Aykardi, and also 49 years with a moderate form of a syndrome.

Treatment of a syndrome of Aykardi:

Treatment of a syndrome of Aykardi is not developed now. The symptomatic treatment is applied. The main strategy of therapy - stopping of infantile spasms which often rezistentna to AEP, treatment their difficult and its efficiency is small. Apply various medicines in the highest doses.

Starting therapy begins with a vigabatrin (sabrit) – 50-100мг/кг/сут and Valproatums (Depakinum syrup) - 50-100мг/кг/сут. At frequent attacks appoint AEP combinations with benzodiazepines (clonazepam) - 0,25-2mg/days, or phenobarbital (5-15мг/кг/сут), and Suxilepum 15-30мг/кг/сут can be also entered.

Alternative method is use of corticosteroid hormones (AKTGG, Synacthenum depot in oil, deksametazy, Prednisolonum – per os) and Ig (octadin). An average dosage of Prednisolonum 1-2,5mg/kg/sut with the subsequent transition to the minimum maintenance dose. Hormones are appointed in combination with basic AEP.

As palliative surgical treatment use of stimulation of a vagus nerve is possible. As musculoskeletal defects can lead to scoliosis, for its prevention the physical therapy, physiotherapy exercises is used, surgical correction is possible.

Families of children with Aykardi's syndrome are given an opportunity to learn about a syndrome, about new discoveries more, to get acquainted with other families, to exchange the ideas and experience and to get useful tips from parents and specialists. Also information on philanthropists conferences and concerts which will organize is regularly posted on the website and finances Aykardi's Fund.