A nationwide survey of Vici syndrome in Japan.

BACKGROUND: Vici syndrome (VICIS) is a congenital disorder characterized by agenesis of the corpus callosum, cataracts, hypopigmentation, cardiomyopathy, combined immunodeficiency, microcephaly, and failure to thrive. This study aimed to elucidate the number of patients with VICIS, its clinical characteristics and relevant genetic information in Japan. METHODS: After developing diagnostic criteria for VICIS, we conducted a nationwide questionnaire-based survey of VICIS in Japan. In the initial survey, we investigated the number of VICIS patients who fulfilled definite or probable criteria. The second survey was used to obtain detailed clinical and genetic information of VICIS from institutions that responded to the initial survey. RESULTS: Clinical information was available for 15 patients (12 definite, three probable). As of October 2023, nine patients (60%) were alive and six (40%) had died. All patients presented with developmental delay, agenesis of the corpus callosum, elevated serum aspartate/alanine aminotransferase, hypopigmentation and hypotonia. Developmental delay was profound. Most patients developed recurrent infection, high-arched palate, epilepsy, failure to thrive, and microcephaly. Cardiomyopathy and cataracts, both initially described as principal features in VICIS, were notably uncommon in our study. Based on the information collected, all 14 patients for whom information was available received home medical care: 11 (79%) received tube feeding, three (21%) required noninvasive ventilation, four (29%) required tracheostomy, and four (29%) required home subcutaneous immunoglobulin administration. CONCLUSION: This study revealed for the first time the nationwide status of patients with VICIS in Japan. The mortality rate of patients with VICIS is as high as 40%, and almost all VICIS patients require various forms of home medical care, necessitating comprehensive management. Additionally, we identified one adult patient, underscoring the need for comprehensive medical management extending into adulthood for patients with VICIS.

Incidence of Hearing Loss in Corpus Callosum Agenesis.

OBJECTIVES: Congenital corpus callosum agenesis (CCA) is one of the congenital anomalies in newborns, which usually presents with syndromic features. It can be asymptomatic or have variable neurological deficits. Some studies demonstrated that hearing loss can occur in patients with CCA; however, the exact prevalence remains unclear. Therefore, we aimed to investigate the prevalence of hearing loss in CCA using data from newborn hearing screening in a single tertiary referral center. METHODS: A total of 126 patients with CCA combined with hearing loss diagnosed at our hospital from November 2005 to November 2022 were retrospectively included in our study. All patients had at least one screening or diagnostic auditory brainstem response result. Brain ultrasonography and magnetic resonance imaging were used to diagnose CCA. RESULTS: Among 126 patients, 93 had automated auditory brainstem response within a month from birth. Of the 93 patients, 20 (21.5%) had a "refer" result in the screening tests in at least one ear. The final incidence of hearing loss in patients with CCA was 16.1%. We observed no hearing loss in 22 patients with isolated CCA. CONCLUSIONS: Patients with CCA have a higher incidence of hearing loss. However, this is likely related to the concurrent condition of patients. CCA seems not to be a risk factor for hearing loss.

Incidence and patterns of abnormal corpus callosum in fetuses with isolated spina bifida aperta.

OBJECTIVE: To determine the incidence and characterise corpus callosum (CC) abnormalities in fetuses with spina bifida aperta (SBA) between 18 and 26 weeks of gestation. METHODS: This was a retrospective study on fetuses with isolated SBA and who were assessed for fetal surgery. Digitally stored ultrasound images of the brain were reviewed for the presence/absence of the CC, and the length and diameter of its constituent parts (rostrum, genu, body and splenium). We used regression analysis to determine the relationship between CC abnormalities and gestational age, head circumference, ventricle size, lesion level and lesion type. RESULTS: Nearly three-quarters of fetuses with isolated SBA had an abnormal CC (71.7%, 76/106). Partial agenesis was most common in the splenium (18.9%, 20/106) and the rostrum (13.2%, 14/106). The most common abnormal pattern was of a short CC with normal diameter throughout. Of note, 20.8% (22/106) had a hypoplastic genu and 28.3% (30/106) had a thick body part. Larger lateral ventricle size was associated with partial agenesis of the CC (odds ratio [OR]: 0.14, p < 0.001) and inversely associated with a shorter CC (OR: 2.60, p < 0.01). CONCLUSION: An abnormal CC is common in fetuses with isolated SBA who are referred for fetal surgery.

Demographic, ocular and associated neurological findings in corpus callosum malformations.

BACKGROUND: The corpus callosum is a primary commissural part of the brain which connects the two hemispheres. Processing sensory, motor, visuo-motor and cognitive functions are related to a healthy connection. In this study, we aimed to evaluate the ocular, neurologic and other systemic findings of corpus callosum malformations and to focus on the association between the ocular and neurological findings and the type of callosal malformation according to cranial magnetic resonance imaging (MRI). METHODS: A retrospective chart review of 57 patients with corpus callosum malformation was performed. Demographic features, neurologic, ocular and other systemic findings were noted. Patients were divided into 3 groups according to the severity of corpus callosum malformation on MRI (total agenesis, partial agenesis and hypoplasia) and also evaluated as a part of a genetic disorder/syndrome or not. The differences between demographic features, ocular and neurological findings between these 3 groups and also between syndromic and non-syndromic groups were evaluated statistically. RESULTS: Only 35.1% of patients had fixation and following pattern of visual acuity. Anterior segment pathologies were observed in 6.9% of patients. However, 57.9% of patients had posterior segment malformations. Only 19.3% of patients had a normal ocular alignment. There was no statistically significant difference of demographic features, ocular and neurologic findings between the 3 groups or between the syndromic/non-syndromic groups. CONCLUSIONS: Ocular findings can be reliable depending on the severity of the corpus callosum malformations. However, delay in fixation reflex development or loss of fixation should remind us of central nervous system pathologies especially corpus callosum malformations.

An analysis of 109 fetuses with prenatal diagnosis of complete agenesis of corpus callosum.

BACKGROUND: Agenesis of the corpus callosum (ACC) is the most frequent commissural malformation of the brain. It continues to be an important cause of the pregnancy termination associated with the central nervous system (CNS). OBJECTIVE: The aim of the study is to provide a comprehensive assessment of fetuses with diagnosis of complete ACC, as well as postnatal neurodevelopmental outcomes. METHODS: The data of 75,843 fetuses were screened for evaluation of complete ACC between 2003 and 2017, and a total of 109 cases with complete ACC were included in the study. ACC was considered isolated when no additional anomalies were detected, and ACC was considered complex when additional anomalies were present. RESULTS: The prevalence of complete ACC was 9.4 per 10,000 live births, and the incidence was ranged from 1.8 to 16.6 per 10,000 person-years. Patients with isolated ACC had a significantly higher survival when compared with patients with complex ACC (97.4%, n = 38/39 vs. 68.8%, n = 22/32, P = 0.001).The most important cause of death were congenital heart disease and/or respiratory failure during neonatal period. Developmental and intellectual disabilities were significantly higher in the complex ACC cases (P < 0.001). Postnatal neurodevelopmental outcomes were completely normal in 79.4% of cases with isolated ACC. CONCLUSIONS: Isolated complete ACC is usually associated with a favorable outcome. The most important prognostic factors are the presence or absence of associated congenital anomalies.

Associated anomalies in cases with agenesis of the corpus callosum.

Agenesis of corpus callosum (ACC) is an uncommon congenital anomaly, its etiology is unclear and its pathogenesis is controversial. Cases with ACC often have other non-ACC associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with ACC were collected in all live births, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population-based registry of congenital malformations. Of the 99 cases with ACC, representing a prevalence of 2.56 per 10,000, 73 (73.7%) had associated anomalies. There were 16 (16.2%) cases with chromosomal abnormalities, and 13 (13.2%) nonchromosomal recognized dysmorphic conditions including syndromes two each: Aicardi, Dandy-Walker, and fetal alcoholism. Forty-four (44.4%) of the cases had nonsyndromic multiple congenital anomalies (MCA). Anomalies in the musculoskeletal, the urogenital, the central nervous, the cardiovascular, and the digestive systems were the most common other anomalies in the cases with MCA. The anomalies associated with ACC could be classified into a recognizable malformation syndrome in 29 out of the 73 cases (39.7%) with associated anomalies. This study included special strengths: it is population-based, each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion the overall prevalence of associated anomalies, three of four cases, emphasizes the need for a screening for other anomalies in cases with ACC.

Clinical presentation of Moyamoya angiopathy in Europeans: experiences from Germany with 200 patients.

INTRODUCTION: Moyamoya angiopathy (MMA) is a rare vasopathy, especially among European Caucasians. Data about demographics, clinical presentation, comorbid conditions, radiological findings as well as laboratory and cerebral spinal fluid (CSF) data are sparse. METHODS: Patients with MMA treated in the Alfried Krupp Hospital, Essen, Germany, between 2010 and 2017 with focus on demographic, clinical, radiological and laboratory as well as CSF data were evaluated retrospectively. Patients with non-Caucasian family background were excluded from this study. RESULTS: Altogether 200 European Caucasian patients with MMA were identified. There was a female predominance of 3.2:1. The mean age at first presentation was 32.9 years and the mean age of diagnosis was 36.0 years. Eleven of 194 index patients (5.7%) showed a familial presentation. In 11.6% posterior cerebral artery was additionally involved, in 4% additionally cerebral aneurysm and in 2.5% dysgenesis of corpus callosum was found. Most patients suffered from transient ischemic attacks (71.5%) and stroke (82%). Cerebral hemorrhage was found in 9.5%. Livedo racemosa was an associated symptom in 12.8% of patients and thyroid diseases were found in 23.8%. CONCLUSIONS: Compared with Asian data, cerebral hemorrhages are infrequent and female predominance is accentuated among European Caucasians. Some former unknown rare features like associated livedo racemosa, dysgenesis of corpus callosum and associated syncope have been discovered systematically for the first time in this huge European Caucasian cohort.

Prevalence and associated factors for agenesis of corpus callosum in Emilia Romagna (1981-2015).

Agenesis and hypoplasia of the corpus callosum (ACC and HCC) are heterogeneous group with a large variation in published prevalence based on few population based studies. The aim of this work is to describe prevalence, associated factors and other malformations present in cases with either agenesis or hypoplasia of the corpus callosum, using a population-based database of all malformations diagnosed in Emilia-Romagna, Italy, (the Emilia-Romagna Registry on Congenital Malformations, IMER). This registry links and integrates hospital discharge records, birth certificates with cases reported by referral clinicians to identify all structural malformations diagnosed within one year of life regarding live birth, fetal death or termination of pregnancy due to fetal malformations (TOPFA). During the study period (1981-2015) the number of cases with ACC or HCC was 255, in a reference population of 1,023,784 live births, giving an overall prevalence of 2.49 per 10,000 (1.47 per 10,000 only live birth). After 1996, with the inclusion of TOPFA in IMER registry, the overall prevalence rate increase significantly from 1.42 to 3.03 cases per 10,000 birth (p-value<0.001). Prenatal diagnosis was made in 192 cases (75.3%), at a median gestational age of 20.7 [IQR: 19.71-22.71]. Termination of pregnancy occurred in 105 of the 255 cases (41,2%). Where a prenatal diagnosis was available, 55% of cases ended in TOPFA (105/192), with higher prevalence of cases associated to central nervous system malformations and multiple birth defects, and median gestational age at diagnosis significantly less than in live birth cases (20.3 vs 29 weeks). Agenesis/hypoplasia ratio was 5.7 (217/38). The most frequently associated malformations were musculoskeletal. Trisomies were the most frequent chromosomal anomalies, in particularly trisomy18 and 13 (respectively 9/32 and 4/32 cases). Our study showed an increased risk for male infants (RR of 1.68, RR 95% CI 1.19-2.37). No differences were detected analyzing maternal age and ethnicity, and the increased risk associated to preterm birth disappeared when compared with other malformed infants. This is one of the few population based studies dealing with prevalence of agenesis and hypoplasia of corpus callosum. Prevalence is still debated, but this study adds comprehensive data, in particular inclusion of TOPFA cases. Early prenatal diagnosis, not always possible, could be crucial for decision making regarding continuation of pregnancy.

Further delineation of Temtamy syndrome of corpus callosum and ocular abnormalities.

Temtamy syndrome is a syndromic form of intellectual disability characterized by ocular involvement, epilepsy and dysgenesis of the corpus callosum. After we initially mapped the disease to C12orf57, we noted a high carrier frequency of an ancient startloss founder mutation [c.1A>G; p.M1?] in our population, and variable phenotypic expressivity in newly identified cases. This study aims to combine 33 previously published patients with 23 who are described here for the first time to further delineate the phenotype of this syndrome. In addition to the known p.M1? founder, we describe four novel homozygous variants, thus increasing the number of Temtamy syndrome-related C12orf57 variants to seven, all but one predicted to be loss of function. While all patients presented with intellectual disability/developmental delay, the frequency of other phenotypic features was variable: 73.2% (41/56) had epilepsy, 63% (34/54) had corpus callosal abnormalities, 14.5% (8/55) had coloboma, and 16.4% (9/55) had microphthalmia. Our analysis also revealed a high frequency of less recognized features such as congenital heart disease (51.4%), and brain white matter abnormalities (38%, 19/50). We conclude that C12orf57 variants should be considered in the etiology of developmental delay/intellectual disability, even when typical syndromic features are lacking, especially in those who trace their ancestry to Saudi Arabia where a founder C12orf57 mutation is among the most common recessive causes of intellectual disability.

Sleep Problems in Children With Agenesis of the Corpus Callosum.

BACKGROUND: Very little is known about sleep habits in children with agenesis of the corpus callosum (ACC). The purpose of this investigation was to evaluate sleep problems in children with ACC and examine the association with quality of life. METHODS: We performed a cross-sectional, anonymous, internet-based survey offered to parents of children with ACC, aged five to 18 years. The Children's Sleep Habits Questionnaire (CSHQ) and pediatric quality of life (PedsQL) were used to assess sleep habits and quality of life, respectively. Associations between the total and all subdomains of CSHQ and PedsQL were tested. RESULTS: The final sample included 66 parents of children with ACC. Overall, 78% of the children had clinically significant sleep problems, using a cutoff score of 41 on the CSHQ. Compared with a prior national sample of typically developing children, children with ACC scored significantly higher overall and in all subdomains of the CSHQ. The overall CSHQ and PedsQL were moderately correlated (r = -0.485, P < 0.001), indicating that children with more sleep problems had worse quality of life. In addition, the total CSHQ correlated with all subdomains of the pediatric quality of life, including emotional (r = -0.515, P < 0.01), social (r = -0.394, P < 0.01), physical (r = -0.263, P < 0.01), and school (r = -0.362, P < 0.01). These associations remained statistically significant in multivariable regression models controlling for age and gender. CONCLUSIONS: Sleep problems are common and associated with lower quality of life in children with ACC.

Role of fetal MRI in the evaluation of isolated and non-isolated corpus callosum dysgenesis: results of a cross-sectional study.

PURPOSE: The aims of this study were to characterize isolated and non-isolated forms of corpus callosum dysgenesis (CCD) at fetal magnetic resonance imaging (MRI) and to identify early predictors of associated anomalies. METHODS: We retrospectively analyzed 104 fetuses with CCD undergoing MRI between 2006 and 2016. Corpus callosum, cavum septi pellucidi, biometry, presence of ventriculomegaly, gyration anomalies, cranio-encephalic abnormalities and body malformations were evaluated. Results of genetic tests were also recorded. RESULTS: At MRI, isolated CCD was 26.9%, the rest being associated to other abnormalities. In the isolated group, median gestational age at MRI was lower in complete agenesis than in hypoplasia (22 vs 28 weeks). In the group with additional findings, cortical dysplasia was the most frequently associated feature (P = 0.008), with a more frequent occurrence in complete agenesis (70%) versus other forms; mesial frontal lobes were more often involved than other cortical regions (P = 0.006), with polymicrogyria as the most frequent cortical malformation (40%). Multivariate analysis confirmed the association between complete agenesis and cortical dysplasia (odds ratio = 7.29, 95% confidence interval 1.51-35.21). CONCLUSIONS: CCD is often complicated by other intra-cranial and extra-cranial findings (cortical dysplasias as the most prevalent) that significantly affect the postnatal prognosis. The present study showed CCD with associated anomalies as more frequent than isolated (73.1%). In isolated forms, severe ventriculomegaly was a reliable herald of future appearance of associated features. © 2016 John Wiley & Sons, Ltd.

Routine Screening for Callosal Dysgenesis in the Second Trimester Is Achievable With Intensive Training.

OBJECTIVES: The purpose of this study was to determine whether routine direct visualization of the corpus callosum is achievable during second-trimester sonography when performed by a large group of sonographers in a general second-trimester sonographic screening program. The secondary aim was to determine the time taken to obtain a sagittal corpus callosum image. METHODS: We conducted a retrospective cohort study of visualization of the corpus callosum before and after intensive training. Images from 150 consecutive second-trimester scans were reviewed before and after training to evaluate the image quality of the corpus callosum. RESULTS: A total of 300 cases were evaluated before and after training. There was a significant increase in the rate of complete visualization of the corpus callosum after intensive training (P < .0001). Before training 35 of 150 cases (23%) had complete visualization of the corpus callosum versus 107 of 150 (71%) after training. The mean time to perform the corpus callosum views was 53.4 seconds before training compared to 56.2 seconds after training. CONCLUSIONS: Assessing the corpus callosum in the sagittal view is difficult and requires appropriate training and patience; however, this view is feasible without adding substantial time to the examination and provides additional information during a routine second-trimester morphologic scan.

Corpus callosum abnormalities: neuroradiological and clinical correlations.

AIM: To study neuroradiological features in pediatric patients with corpus callosum abnormalities, using new functional subtyping for the corpus callosum, and to correlate the features with the clinical presentation. METHOD: We performed a retrospective review of 125 patients with radiologically identified abnormalities of the corpus callosum seen between 1999 and 2012. The study reviewed clinical features, genetic etiology, and chromosomal microarray (CMA) results. We used a new functional classification for callosal abnormalities based on embryological and anatomical correlations with four classes: complete agenesis, anterior agenesis (rostrum, genu, body), posterior agenesis (isthmus, splenium), and complete hypoplasia (thinning). We also studied the presence of extracallosal abnormalities. RESULTS: The new functional callosal subtyping did not reveal significant differences between the various subtypes in association with neurological outcome; however, the presence of cardiac disease was found more frequently in the group with complete agenesis. Thirty-seven per cent (46/125) had identifiable causes: of these, 48% (22/46) had a monogenic disorder, 30% (14/46) had a pathogenic chromosomal copy-number variant detected by CMA or karyotype, and 22% (10/46) had a recognizable clinical syndrome for which no confirmatory genetic test was available (namely Aicardi syndrome/septo-optic dysplasia and Goldenhar syndrome). The diagnostic yield for a significant CMA change was 19%. The presence of Probst bundles was found to be associated with a better neurodevelopmental outcome. INTERPRETATION: The functional classification system alone 'without clinical data' cannot predict the functional outcome. The presence of extracallosal brain abnormalities and an underlying genetic diagnosis predicted a worse neurodevelopmental outcome. This study highlights the importance of CMA testing and cardiac evaluation as part of a routine screen.

Prenatal Diagnosis of Anomalies of the Corpus Callosum over a 13-Year Period.

Purpose: The clinical use of detailed fetal neurosonography has increased over the past decade. This retrospective study explored the spectrum and frequency of different forms of corpus callosum anomalies (CCAs) in a level III center setting. Materials and Methods: Between 1999 and 2012, 48 907 detailed second and third trimester scans were performed. Among them, 140 (0.29 %) cases of CCA were diagnosed. We differentiated between complete and partial agenesis, hypoplastic corpus callosum (CC) and isolated and non-isolated forms. Results: The 140 cases with CCA included 107 with complete agenesis (76 %), 20 with partial agenesis (14 %) and 13 with a hypoplastic CC (9 %). Of them, 29 % (41/140) were isolated and 71 % (99/140) were non-isolated cases. Analysis of three time periods demonstrated an increase in the diagnosis of all types of CCA (1999 - 2004: n = 26; 2005 - 2008: n = 32; 2009 - 2012: n = 82), whereas the ratio between isolated and non-isolated types remained stable. The median gestational age at diagnosis was 25.0 weeks and did not change over the years. Non-isolated forms were associated with additional non-chromosomal cerebral anomalies in 22.2 % (22/99), extracerebral non-chromosomal malformations in 40.4 % (40/99), aneuploidies in 21.2 % (21/99), and syndromes in 16.2 % (16/99). All aneuploid fetuses except one showed cerebral or extracerebral malformations. Conclusion: The rise in prenatal diagnosis of CCA reflects the increased use of systematic fetal neurosonography over the years. Despite an overall increase in diagnosed cases, the relationship between isolated CCAs and complex forms remained stable. Since the percentage of coexisting anomalies is high, a detailed assessment by a specialist is recommended.

Abnormal shape of the cavum septi pellucidi: an indirect sign of partial agenesis of the corpus callosum.

OBJECTIVE: To describe and assess the presence of a new indirect sign of partial agenesis of the corpus callosum (pACC): an abnormally shaped cavum septi pellucidi (CSP). METHODS: We analyzed retrospectively images from all 71 cases of pACC seen at two referral centers between September 2006 and April 2014. Abnormally shaped CSP was diagnosed when its lateral dimension was greater than its anteroposterior dimension in the axial transthalamic plane, and the incidence of this sign was assessed. We also examined the following variables: gestational age at referral, indication for referral, which (if any) of the four corpus callosal segments were abnormal, presence of other, previously established, indirect signs of callosal agenesis (ACC) and presence of additional cerebral or extracerebral anomalies. RESULTS: In 56 of the 71 (79%) cases, the CSP was measurable; it was abnormally shaped in 19 (34%) of these cases, 15 (79%) of which had no other indirect signs of pACC. Of 23 cases with isolated pACC and no other indirect signs, 12 (52%) had an abnormally shaped CSP. CONCLUSIONS: In a significant proportion of cases of pACC detected prenatally, the shape of the CSP is abnormal. This should be considered an additional indirect sign of pACC, and is frequently the only clue to the diagnosis. When observing this sign in a screening context, pACC should be considered, and an attempt to visualize the corpus callosum directly in the midsagittal plane is suggested.

Agenesis of corpus callosum and frontotemporal dementia: a casual finding?

Agenesis of corpus callosum (AgCC) is a congenital malformation characterized by total or partial absence of corpus callosum with a good neuropsychological profile. Frontotemporal dementia (FTD) is the third most common cause of cortical dementia, and it is characterized by alterations in personality and social relationship, often associated with deficits in attention, abstraction, planning, and problem solving. Herein, we report a case of a 73-year-old woman presenting with FTD associated with primary AgCC. The possible "causal or casual" relationship between these 2 different conditions should be investigated in large prospective studies.

Individuals with agenesis of the corpus callosum show sensory processing differences as measured by the sensory profile.

OBJECTIVE: Given reports of high pain thresholds and reduced auditory response in individuals with agenesis of the corpus callosum (AgCC), this study investigated whether affected participants report atypical experiences and behaviors on a well-established sensory processing measure. METHODS: Fourteen participants with AgCC (ages 11-59) completed the Adolescent/Adult Sensory Profile (Brown & Dunn, 2001). Sensory profile scales were classified as "Atypical" if they were more than 1 standard deviation from the mean. RESULTS: Fifty-seven percent of participants with AgCC reported reduced sensory registration as compared to an expected 16% of the normative sample. Similarly, 50% of the AgCC participants reported atypically increased auditory processing difficulties. CONCLUSIONS: Using a well-established sensory processing questionnaire, participants with AgCC reported measurable differences in multiple aspects of sensory processing. The most notable difference was in the quadrant of low sensory registration, suggesting that individuals with AgCC may require sensory information to be presented more slowly or at a higher intensity for adequate processing. The sensory modality that was most affected was the auditory system, which is consistent with increased rates of language disorders and autism spectrum disorders in this population. Understanding sensory processing in individuals with AgCC can both elucidate the role of interhemispheric transfer in the development of intact sensory processing as well as contribute to our knowledge of the role of the corpus callosum in a range of disorders in which sensory processes are impacted. (PsycINFO Database Record

The wide spectrum of tubulinopathies: what are the key features for the diagnosis?

Complex cortical malformations associated with mutations in tubulin genes: TUBA1A, TUBA8, TUBB2B, TUBB3, TUBB5 and TUBG1 commonly referred to as tubulinopathies, are a heterogeneous group of conditions with a wide spectrum of clinical severity. Among the 106 patients selected as having complex cortical malformations, 45 were found to carry mutations in TUBA1A (42.5%), 18 in TUBB2B (16.9%), 11 in TUBB3 (10.4%), three in TUBB5 (2.8%), and three in TUBG1 (2.8%). No mutations were identified in TUBA8. Systematic review of patients' neuroimaging and neuropathological data allowed us to distinguish at least five cortical malformation syndromes: (i) microlissencephaly (n = 12); (ii) lissencephaly (n = 19); (iii) central pachygyria and polymicrogyria-like cortical dysplasia (n = 24); (iv) generalized polymicrogyria-like cortical dysplasia (n = 6); and (v) a 'simplified' gyral pattern with area of focal polymicrogyria (n = 19). Dysmorphic basal ganglia are the hallmark of tubulinopathies (found in 75% of cases) and are present in 100% of central pachygyria and polymicrogyria-like cortical dysplasia and simplified gyral malformation syndromes. Tubulinopathies are also characterized by a high prevalence of corpus callosum agenesis (32/80; 40%), and mild to severe cerebellar hypoplasia and dysplasia (63/80; 78.7%). Foetal cases (n = 25) represent the severe end of the spectrum and show specific abnormalities that provide insights into the underlying pathophysiology. The overall complexity of tubulinopathies reflects the pleiotropic effects of tubulins and their specific spatio-temporal profiles of expression. In line with previous reports, this large cohort further clarifies overlapping phenotypes between tubulinopathies and although current structural data do not allow prediction of mutation-related phenotypes, within each mutated gene there is an associated predominant pattern of cortical dysgenesis allowing some phenotype-genotype correlation. The core phenotype of TUBA1A and TUBG1 tubulinopathies are lissencephalies and microlissencephalies, whereas TUBB2B tubulinopathies show in the majority, centrally predominant polymicrogyria-like cortical dysplasia. By contrast, TUBB3 and TUBB5 mutations cause milder malformations with focal or multifocal polymicrogyria-like cortical dysplasia with abnormal and simplified gyral pattern.

Magnetic resonance imaging findings associated with lateral cerebral ventriculomegaly in English Bulldogs.

Multiple congenital or developmental anomalies associated with the central nervous system have been reported in English Bulldogs. The purpose of this retrospective study was to identify and describe the prevalence and MRI characteristics of these anomalies and their association with presence and degree of cerebral ventriculomegaly. Magnetic resonance imaging studies of 50 English Bulldogs were evaluated. Forty-eight dogs had some degree of cerebral ventriculomegaly, 27 of which had an otherwise normal brain. Presence of lateral ventriculomegaly was not significantly associated with presence of another intracranial lesion. Appearance of the septum pellucidum was variable, ranging from intact to incomplete or completely absent. The corpus callosum was subjectively thinned in all but three dogs, two of which had normal lateral ventricles. Fusion of the rostral colliculi was not found in any dog. A persistent craniopharyngeal canal was identified in one dog. Aqueductal stenosis caused by fusion of the rostral colliculi was not identified in any dog. Findings indicated that cerebral ventriculomegaly is a common finding in English Bulldogs with or without other intracranial lesions, aqueductal stenosis caused by fusion of the rostral colliculi is unlikely to be a common etiology leading to obstructive hydrocephalus, and a large craniopharyngeal canal is a rare finding that has unknown clinical significance at this time.

Agenesis of the corpus callosum associated with spinal open neural tube defect.

OBJECTIVE: To ascertain the incidence and clinical implications of agenesis of the corpus callosum (ACC) in spinal open neural tube defects (SONTD). METHODS: All cases of SONTD registered at the Spina Bifida Clinic in King Khalid University Hospital, Riyadh, Saudi Arabia between 1995 and 2010 were retrospectively reviewed, and mid-sagittal MRI of the corpus callosum (CC) area was analyzed in each case. Neurodevelopmental outcome was classified as poor in children with seizures, severe neurodevelopmental impairment, or death. RESULTS: Thirty-eight patients (45.8%) with ACC were identified among 83 cases with SONTD. Patients' age ranged between one and 16 years. Total ACC was found in 10 patients, partial ACC in 25, and in 3 patients, the CC was hypoplastic. Active hydrocephalus was an associated finding in 9 out of 10 patients with total ACC, 22 out of 25 with partial ACC, and in all patients with hypoplasia of the CC. Thirteen patients (34.2%) had normal intellectual function, whereas 24 patients presented with learning disability, epilepsy, or poor intellectual function; and one patient died of respiratory failure. CONCLUSION: Agenesis of the corpus callosum is found in a significant portion of patients with SONTD. When associated with hydrocephalus, its presence affects neuro-developmental outcome.