The clinical characteristics of children with agenesis of the corpus callosum

doi:10.21203/rs.3.rs-1618205/v1

Objective: To analyze the clinical features of children with agenesis of the corpus callosum in this study due to the lack description at present.

Method: This study retrospectively collected the case data of the agenesis of corpus callosum (ACC) hospitalized in Children's Hospital Affiliated to Chongqing Medical University from January 2015 to October 2021.

Results :1.Classification and typing characteristics: 1.1 Classification according to the absence of anatomical structure of corpus callosum: total absence of corpus callosum in 7 cases (5.8%); partial absent of corpus callosum in 80 cases (66.7%) ;Corpus callosum was thin in 33 cases (27.5%). 1.2 Classification according to presence of extra-callosal craniocerebral malformations:69 children with isolated ACC (57.5%); complex ACC with 51 cases (42.5%). 1.3 Classification based on extracranial structural malformations: 52 children (43.3%) with non-syndromic ACC. 68 cases (56.7%) with syndromic ACC. 2. Clinical features: 70 cases (58.3%) of Gross Developmental Delay, 50 cases (41.7%) of epilepsy, 44 cases (37.3%) of microcephaly, 41 cases (34.2%) of malnutrition, 20 cases (16.7%) of respiratory failure.

Conclusion: Children with agenesis of corpus callosum are often accompanied by abnormalities of other intracranial structures outside the corpus callosum and abnormal structure of extracranial organs. Children with agenesis of the corpus callosum often have neurological diseases, such as gross developmental delay, epilepsy. Secondly, the incidence of malnutrition is also high, especially the severe malnutrition. In addition, some children may also show respiratory failure, so it is necessary to be alert to the possibility of structural abnormalities of the respiratory system. The children with agenesis of the corpus callosum also have a family history of spontaneous abortion in their mothers, patients with neuropsychiatric diseases in their families, and the family history of early death.

agenesis of corpus callosum

generalized developmental delay

epilepsy

chromosome fragment deletion

The corpus callosum is the largest white matter structure in the human brain and contains about 200 million axons. It is present at birth, but myelination of axons persists until puberty. These axons project on the left and right cerebral hemispheres and in the cortex of the hemispheres^[1]. The corpus callosum is a unique structure of placental mammals. Its main function is to transmit information between and within the left and right cerebral hemispheres, including sensory, motor, visual, auditory, language, and cognitive thinking ^[1]^[2]. The corpus callosum can be divided into the genum, rostrum, body, and the splenium according to its anatomical structure. The development of the corpus callosum involves multiple steps, normal neuronal and glial cell proliferation, midline patterning, corpus callosum neuron migration and differentiation, axonal traction and post-guided development^[1]^[3]. Mainly divided into from embryonic development to embryonic 10th week, from neurogenesis to midline commissure formation; embryonic week 11-12 to 20th week, from axon guidance to cross the midline to the formation of the corpus callosum structure; from 20th to 20th week At 30 weeks, the corpus callosum begins to gradually thicken; from embryonic week 30 to 2 months after birth, approximately 21% of the corpus callosum thickness is finely trimmed^[4]. Thus, abnormalities occurring before embryonic week 11 can lead to complete corpus callosum dysplasia, and abnormalities occurring between embryonic weeks 12 and 30 can result in partial corpus callosum absent or thin corpus callosum.

The etiology of ACC is still not completely clear. During the development of the corpus callosum, the development of the corpus callosum can be abnormal due to the influence of genetic factors or environmental factors. Studies have shown that about 30%-45% of ACC is caused by genetic factors. 20%-35%. About 10%-20% are caused by chromosomal abnormalities; metabolic diseases such as pyruvate dehydrogenase deficiency, fumarate deficiency, etc.; environmental factors such as alcohol exposure during pregnancy, prenatal infection, etc^[1].

In humans, studies of corpus callosum function have been demonstrated during corpus callotomy in patients with refractory epilepsy. Although corpus callosotomy has shown control in children with refractory epilepsy, concurrent partial corpus callotomy can also present with severed brain syndrome, a syndrome in which the motor, sensory, auditory, and visual systems are affected ^[5]. Not only that, the function of the corpus callosum can also be studied in adult diseases in which the corpus callosum develops normally, such as corpus callosum vascular infarction, which leads to its loss of function. In a study of adults with corpus callosum infarction, X. Sun et al found that the common manifestations of patients with corpus callosum infarction were intellectual and cognitive impairment along with mild motor and sensory impairment; while for simple corpus callosum infarction, cognitive impairment and intellectual impairment may be is the only early symptom ^[6].

In children, corpus callosum dysplasia is the most common form of corpus callosum abnormality. According to statistics, the incidence of ACC in newborns is about 1.8/10000^[7]. At present, there is no epidemiological study of corpus callosum dysplasia in China, mainly from foreign epidemiological studies. A population-based study by Elisa Ballardini et al. found that the overall incidence was 2.49/10000 (including live births, stillbirths, and terminated fetuses), while the incidence in live births was 1.47/10000 ^[8]. In a prevalence study based on a total of 387,067 cases, including all live births, stillbirths, and terminations of pregnancy, Claude Stoll et al. had 99 cases of corpus callosum dysplasia with an incidence rate of 2.56/10,000 [2]^[. Especially in children with neurodevelopmental disorders, the prevalence of ACC is high, about 2.3%, making it one of the most common disorders of abnormal brain development ^[9]. At present, there are few clinical studies on corpus callosum dysplasia at home and abroad. And most of them are a case report of a syndrome with corpus callosum dysplasia. However, there is a lack of larger samples to specifically discuss its clinical characteristics. Therefore, this paper intends to analyze the clinical characteristics of children with corpus callosum dysplasia.

The subjects of this research group were children with corpus callosum dysplasia who were hospitalized in the Children's Hospital of Chongqing Medical University from January 2015 to October 2021. First, this study was approved by the Ethics Committee of the Children's Hospital Affiliated to Chongqing Medical University. All cases were signed informed consent forms.The case data of children with agenesis of corpus callosum who were hospitalized in Children's Hospital Affiliated to Chongqing Medical University from January 2015 to October 2021 were retrospectively collected, including age at first admission, number of hospitalizations, hospitalization department, birth weight, gestational age, Birth method, maternal pregnancy history, past history, family history, current weight, physical examination, cranial magnetic resonance, EEG, other tests (heart ultrasound, chest CT, developmental scale, X-ray, fibrobronchial mirror, etc.) etc. All the enrolled children in this study underwent head MRI examination in our hospital, and the inspection instruments were mainly GE 3.0T, GE 1.5T, Philips 3.0T and other equipment. At present, there is no uniform classification standard in the world. This study refers to Romina Romaniello et al^[10]. The classification method of corpus callosum is classified as follows: according to the presence or absence of anatomical structure loss, it is divided into complete absent of the corpus callosum (ie, the entire structure of the corpus callosum is not shown), partial absent of the corpus callosum (ie, the corpus callosum is missing an anatomical part but not completely missing), and the corpus callosum is thin. (that is, the anatomy of the corpus callosum is present, but the corpus callosum is thin). According to whether it is accompanied by extra-corpus callosum craniocerebral malformation, it is divided into isolated type and complex type. According to whether it is accompanied by extracranial structural deformities, it is divided into non-syndromic and syndromic.

statistical methods

Microsoft Excel 2010 version was used for data entry and arrangement. Statistical analysis was performed using IBM SPSS statistics 26. Measurement data conforming to normal distribution were expressed as mean ± standard deviation; measurement data with skewed distribution were expressed as median (P25, P75), enumeration data were expressed as cases or percentages, and chi-square test or Fisher's exact test was used for comparison between groups Probability method, with P<0.05 statistically significant.

2.1 General information

The total number of patients in this study was 120, including 73 males and 47 females, with a male-to-female ratio of 1.55:1; the age of the children at first admission showed a skewed distribution, the minimum age was 4 hours, the maximum age was 15 years, and the median age was 9.22 (3.65, 40.25)months, minimum birth weight 1.30kg, maximum 4.30kg, median weight 3.10 (2.5, 3.4)Kg. 21 cases (17.5%) of premature babies; 73 cases (60.8%) of cesarean section. 20 cases (16.7%) had a history of asphyxia; 38 cases (31.7%) had a history of illness during pregnancy; 24 cases (20%) had a history of cold during pregnancy. The number of hospitalizations was 184, with a maximum of 7. The inpatient departments of children cover most departments of internal medicine and surgery.

There were 7 cases (5.8%) of abnormal B-ultrasound examinations during pregnancy, including 2 cases of intracranial cyst, 4 cases of hydrocephalus, 1 case of bilateral ventriculomegaly, 1 case of cerebral dysplasia, and 1 case of cardiac malformation. Special face was found in 34 cases (28.3%), 44 cases (37.3%) with Microcephaly. Malnutrition in 41 cases (34.2%). 12 were moderately malnourished and 29 were severely malnourished. There were 24 cases of positive family history, of which 14 cases of maternal history of spontaneous abortion; 5 of them had a history of more than 2 spontaneous abortions. There were 3 cases of family history of premature death, 7 cases of family history of neurological diseases (including 1 case of febrile convulsion, 4 cases of intellectual disability, 3 cases of epilepsy, of which 1 case had both epilepsy and intellectual disability), and 1 case of congenital heart disease.

Table 1 Summary of family history of 24 children
Number	Abnormal family history
1	Mother G1 spontaneous abortion
2	Grandma has "congenital heart disease"
3	The history of the father's heat shock
4	Both mothers G1 and G2 stopped miscarriage due to fetal heartbeat at 3 months of pregnancy
5	The mothers G1, G2, and G3 all had spontaneous abortions due to "septal uterus and intrauterine adhesions"
6	Mother G1 stopped miscarriage due to fetal heartbeat at 3 weeks of pregnancy
7	The mother suffers from "intellectual disability"
8	The elder brother or elder sister (unknown) of the child suffered from "congenital heart disease, convulsions, congenital laryngeal cartilage dysplasia" after birth, and later died of convulsions
9	The mother suffers from "epilepsy"
10	The mothers G1 and G2 had unexplained spontaneous abortion. The sister of the child suffers from "epilepsy and mental retardation".
11	The mother had aborted once in the third month of pregnancy
12	The mother's G2 pregnancy stopped at 30 weeks
13	The mother has "mental retardation", and the G1 is stillborn at full term
14	Mother's history of 3 previous spontaneous abortions
15	Mother G2 spontaneous abortion
16	The father suffers from "schizophrenia" and the elder brother of the child suffers from "abnormal intelligence"
17	Mother spontaneously miscarried 1 time
18	One brother died of "lung dysplasia and diaphragmatic hernia" shortly after birth
19	Mother G6 spontaneous abortion
20	mother spontaneously miscarried 1 time
21	The grandfather of the child suffers from "epilepsy"
22	Mother G3 spontaneous abortion
23	Both mothers G3 and G4 had spontaneous abortions
24	3 older brothers died due to "congenital deformities and severe infections" after birth

There were 69 cases (57.5%) of isolated ACC , and 51 (42.5%) children with complex ACC. Including 22 cases of intracranial cyst, 13 cases of brain atrophy, 9 cases of gray matter heterotopia, 7 cases of polymicrogyria, 5 cases of megagyrus, 5 cases of lipoma, 4 cases of cerebellar dysplasia, 2 cases of meningocele, There were 2 cases of schizencephaly, 2 cases of holoencephaly, 2 cases of tuberous sclerosis, and 1 case of simplified gyrus. There were 2 cases of dandy-Walker syndrome and 1 case of joubert syndrome. Secondly, 79 cases (65.8%) had ventricular dilatation, and 78 cases (65%) had abnormal ventricular morphology. White matter myelination was delayed in 29 cases (24.2%).Among them, 36 cases (30%) had 1 abnormality in other intracranial structures; 10 cases (8.3%) had 2 abnormalities in other intracranial structures; and 5 cases (4.2%) had 3 abnormalities in other intracranial structures.

There were 52 children with non-syndromic ACC (43.3%). There were 68 children (56.7%) with syndromic ACC. In this study, 35 cases (29.2%) of congenital heart disease, 23 cases (19.2%) of musculoskeletal system abnormalities, 19 cases (15.8%) of respiratory system abnormalities, 13 cases (10.8%) of urogenital system abnormalities, and 10 cases of auditory system abnormalities cases (8.3%), 9 cases (7.5%) with abnormal visual system, 2 cases (1.7%) with abnormal blood system, and 1 case (0.8%) with abnormal digestive system. For details, see Table 3 below:

Table 2 Summary of extracranial system abnormalities
extracranial system abnormalities	Number of people
congenital heart disease	35
Atrial Septal Defect	20
Patent foramen ovale	13
Patent ductus arteriosus	10
ventricular septal defect	3
Coarctation of the aorta	1
Aortic valve prolapse of right coronary valve	1
Musculoskeletal System	23
Rib deformity or pectus excavatum or flat chest	5
Enamel Dysplasia	1
Deformity of the finger or toe joint	4
hip dysplasia	4
Missing nasal septum	1
joint contracture	2
Cleft Palate	2
Polydactyly	1
Inversion	2
cubitus varus	1
Scoliosis	3
Congenital dislocation of the radial head	1
Torticollis	3
Dysplasia of the Respiratory System	19
Congenital laryngeal chondrodysplasia	11
Bronchial stenosis	10
Tracheobronchi	1
Right lung 2 lobes	1
Bronchopulmonary dysplasia	4
Bronchomalacia	2
Tracheal Diverticulum	1
Genitourinary system abnormalities	13
Cryptorchidism	6
Inguinal Hernia	4
Renal cyst or polycystic kidney	1
Posterior urethral valve	1
Left kidney ectopic	1
Hearing System Abnormalities	10
Hearing screening or brainstem auditory evoked potential abnormalities	10
Vision System Abnormalities	9
congenital cataract	1
Visually Impaired	2
Retinal exudate with refractive error	1
Morning glory syndrome (congenital optic disc dysplasia)	1
squint	4
Blood System Abnormalities	2
Fanconi Anemia	1
Alpha Thalassemia	1
Digestive System Abnormalities	1
Congenital pyloric obstruction	1

Note:One person can have multiple system abnormalities, and one system can have multiple abnormalities.

70 cases (58.3%) of gross developmental delay. There were 33 children with developmental assessment test, one of whom had Wechsler's total IQ score of 72, which was at the borderline level. The rest of the children had different degrees of developmental delay. 50 cases (41.7%) of epilepsy. Respiratory failure occurred in 20 cases (16.7%), of which 18 were due to bronchopneumonia and 2 were due to status of convulsions.

Table 3 Comparison of clinical characteristics of children with complete absent of corpus callosum, partial absent of corpus callosum, and thin corpus callosum
Clinical characteristics	Total number	Complete absence of corpus callosum N=7（%）	Partial absence of corpus callosum N=80（%）	Thin corpus callosum N=33（%）	Chi-square value	P value
GDD	70	5（71.4）	45（56.3）	20（60.6）	0.659	0.778
Microcephaly	44	3（42.9）	33（41.3）	8（24.2）	3.12	0.225
Epilepsy	50	5（71.4）	35（43.8）	10（30.3）	4.306	0.113
Malnutrition	41	1（14.3）	31（38.8）	9（27.3）	2.387	0.274
Respiratory failure	20	1（14.3）	12（15）	7（21.2）	0.824	0.768

Table 4 Comparison of clinical features of children with simple ACC and complex ACC
Clinical characteristics	Total number	Simple N=69（%）	Complex N=51（%）	Chi-square value	P value
GDD	70	42（60.9）	28（54.9）	0.430	0.512
Microcephaly	44	23（33.3）	21（41.2）	0.777	0.378
Epilepsy	50	23（33.3）	27（52.9）	4.639	0.031*
Malnutrition	41	23（33.3）	18（35.3）	0.05	0.823
Respiratory failure	20	11（15.9）	9（17.6）	0.061	0.804

Table 5 Comparison of clinical characteristics of children with non-syndromic ACC and syndromic ACC
Clinical characteristics	Total number	non-syndromic N=52（%）	syndromic N=68（%）	Chi-square value	P value
GDD	70	33（63.5）	37（54.4）	0.993	0.319
Microcephaly	44	12（23.1）	32（47.1）	7.298	0.007*
Epilepsy	50	26（50）	24（35.3）	2.622	0.105
Malnutrition	41	8（15.4）	33（48.5）	14.392	0.000*
Respiratory failure	20	3（5.8）	17（25）	7.846	0.005*

Table 6 Comparison of the relationship between GDD and non-GDD group in epilepsy, microcephaly
	Non-GDD N=50（%）	GDD N=70（%）	Chi-square	P value
Epilepsy	15（30）	35（50）	4.800	0.028*
Microcephaly	11（22）	33（47.1）	7.94	0.005*

Note："*" means P<0.05 for this group.GDD-Gross decelopmental delay.

The clinical and neurobehavioral outcomes of patients with agenesis of corpus callosum was varied, ranging from asymptomatic to varying degrees of cognitive impairment, even within the same type of ACC. Studies have shown that the core symptoms of patients with agenesis of corpus callosum mainly include reduced transmission of sensory-motor information; increased cognitive processing time; and lack of ability to process complex information or tasks ^[11]. Even in the adult ACC population with normal intellectual development, different degrees of abnormal decision-making ability can occur. Ryan W. Mangum et al. analyzed 36 ACC adults with normal intelligence and showed that ACC individuals have mild to moderate executive function problems in daily behavior. And ACC individuals lack self-understanding or insight into the severity of these problems ^[12].

In this study, including 73 males and 47 females, with a male-to-female ratio of 1.55:1. This shows that there are significantly more male children than female children. In terms of birth weight, The median body weight was 3.1kg (2.5, 3.4), which was basically in line with the average weight range of normal newborns. In addition, in terms of the number of hospitalizations, 45% of the children had more than 2 hospitalizations. This aspect shows that the diseases complicated by these children are of a chronic nature, and there is the possibility of re-hospitalization, which increases the burden on the families and society of the children to a certain extent in China.

The types of corpus callosum dysplasia was varied among studies. Claude Stoll et al. analyzed 99 children with agenesis of the corpus callosum and found that 79.8% of the children had a complete absence of corpus callosum, 8.1% had a partial deletion, and 12% had a thin corpus callosum. The complete absence of corpus callosum is the predominant form^[2]. In a prognostic study of 61 children with agenesis of corpus callosum, Lucia Margari found that 3 (4.9%) had complete deletions, 7 (13%) had partial deletions, and 49 (82%) had partial deletions. A thin corpus callosum appears ^[13]. By comparison, it can be found that the results of these two are significantly different from the type of corpus callosum dysplasia in this study. In this study, the corpus callosum was completely absent in 7 cases (5.8%), partially absent in 80 cases (66.7%), and thin in 33 cases (27.5%). The main form of corpus callosum dysplasia is the absence of part of the corpus callosum. This suggests that there may be racial differences. In addition, agenesis of corpus callosum is often accompanied by other intracranial structural abnormalities. In this study, there were 51 patients with complex ACC, accounting for 42.5%. In addition, children with agenesis of corpus callosum were often accompanied by ventricular dilatation and abnormal ventricular morphology. These findings suggest that agenesis of corpus callosum is often accompanied by abnormal development of other brain structures. In this study, 32 patients had more than twice MRI examinations, of which only 1 patient with thin corpus callosum was recovered normal in the later re-examination, and the other 31 children had no significant changes in multiple re-examinations. This suggests that congenital agenesis of corpus callosum is difficult to return to normal.

The proportion of ACC with extracranial dysplasia has also been inconsistent across studies. In the study of Romina Romaniello et al, about 69% of children had abnormal development of extracranial organs ^[10]. In the study of Hye-Ryun Yeh et al., about 22.4% of the children had abnormal development of extracranial organs ^[14]. This study found that the proportion of children with ACC accompanied by abnormal development of extracranial organs was 56.7%. In the study of AQEELAHAL-HASHIM et al., 46% of the children had abnormal vision ^[15]. This is significantly different from this study, which indicates that children with ACC need to pay attention to undetectable vision abnormalities and hearing abnormalities, and improve vision and hearing screening as soon as possible. When comparing syndromic ACC with non-syndromic ACC, it was found that the incidence of microcephaly in the former was significantly higher than that in the latter (47.1% VS 23.1%), P=0.007, with a statistically significant difference. This suggests that when there is microcephaly in children with ACC, it is also necessary to be alert to the abnormal development of extracranial system organs.

Several studies have shown that the prognostic results of different studies are quite different. In a 25-person study, Lise Folliot et al found that isolated ACC had a better prognosis, with normal gross motor development in 88% of cases. Children have normal or mild neurodevelopmental delay, with only 12 percent experiencing moderate/severe neurodevelopmental delay ^[16]. In a study of 61 children with ACC, Lucia Margari et al. found that 81.3% of children with isolated ACC had intellectual disability ^[13]. Through the analysis of 120 children with ACC, 70 of them had gross developmental delay, accounting for 58.3%, indicating that the overall prognosis of children with ACC was poor. In addition, the median age at the time of first admission in this study was 9.22 months, which indicates that most of the children had gross developmental delay and did not seek medical attention in time. Therefore, early and timely follow-up is necessary for the early detection of agenesis of corpus callosum. There was no statistically significant difference in the incidence of gross developmental delay between the groups with complete absent of the corpus callosum and the group with partial absence and the thin corpus callosum group. At the same time, there was no statistical difference in the incidence of gross developmental delay between the isolated ACC group and the complex ACC group. In addition, there was no statistical difference in the incidence of gross developmental delay between the syndromic group and the non-syndromic group. This may be due to the fact that most of the inpatients in our hospital have brain MRI examinations due to abnormal neurological manifestations. Therefore, the proportion of children with gross developmental delay in the study is relatively high. The prognosis of different research results varies greatly, which may be related to the current research methods, follow-up time, regions and other factors.

Studies have found that about two-thirds of patients with ACC have seizures, but ACC is not an indicator of epilepsy, and other brain structural abnormalities, such as cortical dysplasia, are more often present in children with epilepsy ^[17]. In this study, there were 50 cases of epilepsy, accounting for 41.7%, including 12 cases of infantile spasms (a refractory epilepsy syndrome). This is consistent with the findings of Romina Romaniello et al., who found that the incidence of epilepsy in children with ACC was 41%, of which 21% were intractable epilepsy ^[10]. In addition, there were 5 cases of clinical discharge in this study. The above indicated that the children with agenesis of corpus callosum in this study had a higher incidence of epilepsy. In terms of structural factors, the incidence of epilepsy in the complex ACC group was higher than that in the simple ACC group (52.9% VS 33.3%), P=0.031, with a statistically significant difference. This is also reflected in the study by Lucia Margari et al ^[13]. This also shows that children with ACC have a higher incidence of epilepsy, those with other brain structural abnormalities have a higher incidence of epilepsy, which has an important impact on the occurrence of epilepsy. In children, cortical dysplasia is the most common lesion in structural epilepsy. At the prognostic level, compared with the non-syndromic group, the ACC children in the syndromic group had a higher rate of epilepsy (50% VS 30%), P=0.028, with a statistically significant difference. Repeated epileptiform discharges and epileptic seizures are more likely to lead to epileptic encephalopathy in children, especially infancy and early childhood, when the brain is developing rapidly, leading to a poor prognosis.

In this study, a total of 20 children with ACC had respiratory failure, accounting for 16.7%, of which 18 were caused by severe bronchopneumonia and 2 were caused by status of convulsions. The incidence of respiratory failure in children with syndromic ACC was significantly higher than that in children with non-syndromic ACC (25% VS 5.8%). P=0.005, with statistical difference. Among the 20 children with respiratory failure, 12 had structural abnormalities of the respiratory system. Therefore, it is shown that children with abnormal airway development are more prone to respiratory failure. In this study, children with ACC had a higher incidence of respiratory failure. In addition, children with ACC combined with congenital respiratory dysplasia had a higher incidence of respiratory failure. However, there is no separate analysis of respiratory failure in children with corpus callosum dysplasia in literature. Therefore, children with ACC should try to avoid respiratory infections in their daily lives.

There are no studies that describe the nutritional status of children with ACC individually. Studies have shown that the incidence of malnutrition in children with cerebral palsy ranges from 29% to 46%, and feeding difficulties are mainly caused by uncoordinated swallowing, gastroesophageal reflux, delayed gastric emptying, repeated vomiting, poor intestinal peristalsis, and constipation^[18]. Studies have found that malnutrition in children with cerebral palsy can reduce bone density and increase the risk of fractures, reduce muscle tissue and cause physical weakness, lack of adequate nutrition to support the development of the nervous system leads to further development, lower immunity and increase the risk of infection, and increase the risk of death^[19]. In this study, 41 children with malnutrition were found, accounting for 34.2%. Among them, severe malnutrition is the main type. Among children with syndromic ACC and non-syndromic ACC, the incidence of malnutrition in the former was significantly higher than that in the latter (48.5% VS 15.4%), P=0, with a statistically significant difference. It shows that the incidence of malnutrition in children with ACC is higher, especially in the case of abnormal development of the extracranial system. Therefore, clinical attention should be paid to the malnutrition of children with ACC. In order to early detection and strengthen nutrition and care, especially ACC with abnormal development of extracranial organs.

In children with agenesis of corpus callosum is often accompanied by abnormal intracranial structures outside the corpus callosum and abnormal development of extracranial organ structures. Children with agenesis of corpus callosum often have neurological disease manifestations, such as gross developmental delay, epilepsy. secondly, the incidence of malnutrition is also high, and severe malnutrition is the main type; in addition, some children can occur respiratory failure, and the possibility of structural abnormalities of the respiratory system should be alerted. Children with agenesis of corpus callosum are also abnormal in the family history, mainly manifested by the mother's history of spontaneous abortion, patients with neuropsychiatric diseases in the family, and family history of premature death.

ACC:agenesis of corpus callosom

GDD:gross developmental delay

G:gestation

MRI: magnetic resonance imaging

EEG: electroencephalogram

CT: computerized tomography

Ethics approval and consent to participate

Our study was approved by the ethics committee of the Children's Hospital Affiliated to Chongqing Medical University,File: No. 418 of 2021 year. All cases were signed informed consent forms.

Consent for publication

All authors consent for publication

Availability of data and material

Our data were from our hospital database,were credible.

Competing interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The study was not funded.

Authors' contributions

Duan Yuanhui and Cao Jie contributed to the design, contributed to data acquisition, analysis and interpretation, drafted the manuscript and contributed to subsequent revisions, critically revised the manuscript.All authors provided final approval of the finished manuscript.

Acknowledgements

The authors thank the patients and their parents for their cooperation during the diagnostic process.

Palmer EE, Mowat D. Agenesis of the corpus callosum: a clinical approach to diagnosis. Am J Med Genet C Semin Med Genet. 2014 Jun;166C(2):184-197.
Stoll C, Dott B, Roth MP. Associated anomalies in cases with agenesis of the corpus callosum. Am J Med Genet A. 2019 Oct;179(10):2101-2111.
Paul LK, Brown WS, Adolphs R, Tyszka JM, Richards LJ, Mukherjee P, Sherr EH. Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nat Rev Neurosci. 2007 Apr;8(4):287-99.
De León Reyes NS, Bragg-Gonzalo L, Nieto M. Development and plasticity of the corpus callosum. Development. 2020 Sep 28;147(18):dev189738.
Jea A, Vachhrajani S, Widjaja E, Nilsson D, Raybaud C, Shroff M, Rutka JT. Corpus callosotomy in children and the disconnection syndromes: a review. Childs Nerv Syst. 2008 Jun;24(6):685-92.
Sun X, Li J, Fan C, Zhang H, Si Y, Fang X, Guo Y, Zhang JH, Wu T, Ding S, Bi X. Clinical, neuroimaging and prognostic study of 127 cases with infarction of the corpus callosum. Eur J Neurol. 2019 Aug;26(8):1075-1081.
Glass HC, Shaw GM, Ma C, Sherr EH. Agenesis of the corpus callosum in California 1983-2003: a population-based study. Am J Med Genet A. 2008 Oct 1;146A(19):2495-500.
Ballardini E, Marino P, Maietti E, Astolfi G, Neville AJ. Prevalence and associated factors for agenesis of corpus callosum in Emilia Romagna (1981-2015). Eur J Med Genet. 2018 Sep;61(9):524-530.
Jeret JS, Serur D, Wisniewski K, Fisch C. Frequency of agenesis of the corpus callosum in the developmentally disabled population as determined by computerized tomography. Pediatr Neurosci. 1985-1986;12(2):101-3.
Romaniello R, Marelli S, Giorda R, Bedeschi MF, Bonaglia MC, Arrigoni F, Triulzi F, Bassi MT, Borgatti R. Clinical Characterization, Genetics, and Long-Term Follow-up of a Large Cohort of Patients With Agenesis of the Corpus Callosum. J Child Neurol. 2017 Jan;32(1):60-71.
Brown WS, Paul LK. The Neuropsychological Syndrome of Agenesis of the Corpus Callosum. J Int Neuropsychol Soc. 2019 Mar;25(3):324-330.(新增)
Mangum RW, Miller JS, Brown WS, Nolty AAT, Paul LK. Everyday Executive Function and Self-Awareness in Agenesis of the Corpus Callosum. J Int Neuropsychol Soc. 2021 Nov;27(10):1037-1047.（新增）
Margari L, Palumbi R, Campa MG, Operto FF, Buttiglione M, Craig F, Matricardi S, Verrotti A. Clinical manifestations in children and adolescents with corpus callosum abnormalities. J Neurol. 2016 Oct;263(10):1939-45.
Yeh HR, Park HK, Kim HJ, Ko TS, Won HS, Lee MY, Shim JY, Yum MS. Neurodevelopmental outcomes in children with prenatally diagnosed corpus callosal abnormalities. Brain Dev. 2018 Sep;40(8):634-641.
Al-Hashim AH, Blaser S, Raybaud C, MacGregor D. Corpus callosum abnormalities: neuroradiological and clinical correlations. Dev Med Child Neurol. 2016 May;58(5):475-84.
Folliot-Le Doussal L, Chadie A, Brasseur-Daudruy M, Verspyck E, Saugier-Veber P, Marret S; Perinatal Network of Haute-Normandie. Neurodevelopmental outcome in prenatally diagnosed isolated agenesis of the corpus callosum. Early Hum Dev. 2018 Jan;116:9-16
Unterberger I, Bauer R, Walser G, Bauer G. Corpus callosum and epilepsies. Seizure. 2016 Apr;37:55-60
Batra A, Beattie RM. Recognising malnutrition in children with neurodisability. Clin Nutr. 2020 Feb;39(2):327-330.
Jesus AO, Stevenson RD. Optimizing Nutrition and Bone Health in Children with Cerebral Palsy. Phys Med Rehabil Clin N Am. 2020 Feb;31(1):25-37.

No competing interests reported.

The clinical characteristics of children with agenesis of the corpus callosum

Status:

Version 1

Abstract

Figures

Introduction

1. Materials And Methods

2. Results

3. Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1