Fetal and neonatal outcomes of posterior fossa anomalies: a retrospective cohort study.

The primary aim of this study was to estimate the incidence of posterior fossa anomalies (PFA) and assess the associated outcomes in King Abdulaziz Medical City (KAMC), Riyadh. All fetuses diagnosed by prenatal ultrasound with PFA from 2017 to 2021 in KAMC were analyzed retrospectively. PFA included Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC), and isolated vermian hypoplasia (VH). The 65 cases of PFA were 41.5% DWM, 46.2% MCM, 10.8% VH, and 1.5% BPC. The annual incidence rates were 2.48, 2.64, 4.41, 8.75, and 1.71 per 1000 anatomy scans for 2017, 2018, 2019, 2020, and 2021, respectively. Infants with DWM appeared to have a higher proportion of associated central nervous system (CNS) abnormalities (70.4% vs. 39.5%; p-value = 0.014) and seizures than others (45% vs. 17.9%; p-value = 0.041). Ten patients with abnormal genetic testing showed a single gene mutation causing CNS abnormalities, including a pathogenic variant in MPL, C5orf42, ISPD, PDHA1, PNPLA8, JAM3, COL18A1, and a variant of uncertain significance in the PNPLA8 gene. Our result showed that the most common PFA is DWM and MCM. The autosomal recessive pathogenic mutation is the major cause of genetic disease in Saudi patients diagnosed with PFA.

Not Dandy Walker variant: a review of prominent retrocerebellar CSF space in children.

The prominent retrocerebellar cerebrospinal fluid (CSF) space can be frequently encountered on paediatric neuroimaging studies. In cases involving abnormal vermian development where imaging does not align with the established criteria of Dandy-Walker malformation (DWM), the term "Dandy-Walker variant or continuum" has been historically employed to describe the aberrant posterior fossa development. Instead, the emphasis is on a more elaborate description of the findings in the posterior fossa. Moreover, combining the findings in the supratentorial brain can occasionally predict certain neurogenetic disorders that mimic Dandy-Walker phenotype. The present review demonstrates and differentiates the imaging features of various entities that result in an enlarged retrocerebellar CSF space, such as inferior vermian hypoplasia (IVH) and several neurogenetic conditions.

Meckel-Gruber syndrome together with Dandy-Walker malformation: an atypical case report of a 2nd recurrence in a consanguine marriage.

Meckel-Gruber syndrome is a lethal disorder characterized by occipital encephalocele, polycystic kidneys, and polydactyly. In most cases, it is identified and terminated antenatally. In this report, the authors present a case of Meckel-Gruber syndrome together with Dandy-Walker malformation. A pregnant woman referred at the 28th week of gestation with an abnormal ultrasound scan showing posterior encephalocele and bilaterally enlarged kidneys. Further imaging also indicated communication between the 4th ventricle and posterior cerebellar cerebrospinal fluid space, after which the fetus was diagnosed with Meckel-Gruber syndrome and Dandy-Walker malformation. Pregnancy termination was refused by the parents and the offspring was prematurely born to be the 2nd recurrence of Meckel-Gruber syndrome in this consanguine family. Remarkably, at the 3 different pregnancies, ultrasound was inconclusive before the 7th month of gestation. Though up to date Meckel-Gruber syndrome is ultimately lethal, the lifespan of affected newborns varied greatly. We suggest developing a severity classification to estimate life expectancy in unterminated cases.

Dandy-Walker Phenotype with Brainstem Involvement: 2 Distinct Subgroups with Different Prognosis.

BACKGROUND AND PURPOSE: Although cardinal imaging features for the diagnostic criteria of the Dandy-Walker phenotype have been recently defined, there is a large range of unreported malformations among these patients. The brainstem, in particular, deserves careful attention because malformations in this region have potentially important implications for clinical outcomes. In this article, we offer detailed information on the association of brainstem dysgenesis in a large, multicentric cohort of patients with the Dandy-Walker phenotype, defining different subtypes of involvement and their potential clinical impact. MATERIALS AND METHODS: In this established multicenter cohort of 329 patients with the Dandy-Walker phenotype, we include and retrospectively review the MR imaging studies and clinical records of 73 subjects with additional brainstem malformations. Detailed evaluation of the different patterns of brainstem involvement and their potential clinical implications, along with comparisons between posterior fossa measurements for the diagnosis of the Dandy-Walker phenotype, was performed among the different subgroups of patients with brainstem involvement. RESULTS: There were 2 major forms of brainstem involvement in patients with Dandy-Walker phenotype including the following: 1) the mild form with anteroposterior disproportions of the brainstem structures "only" (57/73; 78%), most frequently with pontine hypoplasia (44/57; 77%), and 2) the severe form with patients with tegmental dysplasia with folding, bumps, and/or clefts (16/73; 22%). Patients with severe forms of brainstem malformation had significantly increased rates of massive ventriculomegaly, additional malformations involving the corpus callosum and gray matter, and interhemispheric cysts. Clinically, patients with the severe form had significantly increased rates of bulbar dysfunction, seizures, and mortality. CONCLUSIONS: Additional brainstem malformations in patients with the Dandy-Walker phenotype can be divided into 2 major subgroups: mild and severe. The severe form, though less prevalent, has characteristic imaging features, including tegmental folding, bumps, and clefts, and is directly associated with a more severe clinical presentation and increased mortality.

Asymptomatic Dandy Walker Malformation In An Elderly Male With Acute Haemorrhagic Stroke - A Case Report.

Dandy-Walker Malformation (DWM) is a rare congenital anomaly of the posterior cranial fossa. Features of DWM include hypoplasia of the cerebellar vermis, enlargement of the posterior fossa, and cystic dilatation of the fourth ventricle. MRI is the modality to confirm the diagnosis. Treatment is usually symptomatic and required when signs of hydrocephalus develop. Rare cases of asymptomatic DWM diagnosed incidentally are reported in literature. We report a case of DWM in a 60-year-old male who presented with haemorrhagic stroke and was later found to have DWM on brain imaging.

Congenital melanocytic naevus syndrome and Dandy-Walker malformation - a mistaken association: case report and literature review.

Congenital melanocytic naevus (CMN) syndrome, previously termed neurocutaneous melanosis, is a rare disease caused by postzygotic mosaic mutations occurring during embryogenesis in precursors of melanocytes. The severity of neurological manifestations in CMN patients is related to central nervous system abnormalities found at magnetic resonance imaging. The association between CMN and Dandy-Walker malformation (DWM) has been described in the literature, but recent advances in imaging and genetics lead to diagnostic criteria revision. In this paper, we aim to re-evaluate the proposed association by reviewing the available literature and present a patient with CMN and a large posterior fossa cyst.

The Management of Hydrocephalus in Midline Posterior Fossa Cystic Collections: Surgical Outcome From a Retrospective Single-Center Case Series of 54 Consecutive Pediatric Patients.

BACKGROUND: Hydrocephalus frequently occurs with midline posterior fossa cystic collections. The classification of this heterogeneous group of developmental anomalies, including Dandy-Walker malformation, persisting Blake's pouch, retrocerebellar arachnoid cysts, and mega cisterna magna, is subject of debate. The absence of diagnostic criteria is confusing regarding the ideal management of PFCC-related hydrocephalus. OBJECTIVE: To decipher the surgical strategy for the treatment of children with PFCC-related hydrocephalus through a retrospective analysis of the surgical outcome driven by their clinical and radiological presentation. METHODS: This study enrolled patients operated of symptomatic PFCC-related hydrocephalus. Clinical and MRI features were examined, as well as the surgical outcome. Unbiased subgroup classification of the patients was performed with multiple component analysis as a function of imaging characteristics and hierarchical clustering on principal component. Outcome was assessed with binomial logistic regression and Kaplan-Meier analysis. RESULTS: Fifty-four patients were included between 2007 and 2021. Multiple component analysis suggested that cerebellar and vermian hypoplasia, vermian rotation, basal-tentorial angle, and fastigial angle were strongly correlated. Hierarchical clustering and the distribution of the patients in the bidimensional plot showed the clear segregation of 3 major clusters, which correlated with the radiological diagnosis ( P < .01). Binomial logistic regression and survival analysis showed that endoscopic third ventriculostomy was an effective treatment for patients with persisting Blake's pouch, while failing to control hydrocephalus in most of patients with Dandy-Walker malformation. CONCLUSION: Preoperative MRI in patients with PFCC-related hydrocephalus is essential to better define the diagnosis. The choice of treatment strategy notably relies on correct radiological diagnosis.

Dandy-Walker malformation and variants: clinical features and associated anomalies in 28 affected children-a single retrospective study and a review of the literature.

OBJECTIVE: To investigate the clinical characteristics, the neuroimaging features and associated anomalies observed in children affected by Dandy-Walker malformations (DWM) and variants (DWV) in a single tertiary hospital in Catania and compare our data to their existent in the literature. METHODS: A retrospective case series using the medical records has been performed on 28 children diagnosed with DWM and DWV admitted to a single tertiary section of Pediatric Neurology, Department of Catania, Italy from January 2005 to January 2021. We reviewed the neuroimaging using the new diagnostic criteria of Klein et al. RESULTS: Associated anomalies were frequently reported. Among these, hydrocephalus was found in 13/28 (48%), and hydrocephalus plus corpus callosum anomalies in three children (10%). We described corpus callosum, cardiac and genitourinary anomalies in 2/28 (7%), 3/28 (10%), and 3/28 (10%), respectively. The most common clinical features were the developmental delay and epilepsy observed in 19/28 (67%) and in 9/28 (32%) of the cases. The first exam at the diagnosis was MRI in 17/28 patients, followed by transfontanellar ultrasound in 5/28, computed tomography in 4/28 and prenatal ultrasound in 2/28. To note, a child with DWM was affected by Down syndrome and one by congenital disorders of N-linked glycosylation (CDG-IId). CONCLUSIONS: Children with DWV were more commonly observed than children with DWM. Hydrocephalus is an anomaly, frequently and equally reported in both DWM and DMV. Perinatal complications were frequent adverse events with severe respiratory distress and need for cardiopulmonary resuscitation. Cognitive involvement and epilepsy were the most common comorbidities. Single DWV is associated with a better developmental outcome.

Endoscopic ultrasonic aspiration of posterior fossa abscess in Dandy-Walker malformation: case report.

BACKGROUND: Dandy-Walker malformation (DWM) is a posterior fossa malformation characterized by a huge posterior fossa cyst in communication with the fourth ventricle. Hydrocephalus is associated with more than 80% of cases and is usually treated by shunting. Despite infection being a common complication of the shunt, abscess formation within the cyst was reported only once. CASE REPORT: A neonate affected by DWM developed a posterior fossa abscess following a shunt infection. The purulent collection was refractory to standard treatment (antibiotics and burr hole drainage); therefore, an endoscopic approach was performed in order to remove the purulent collection under direct vision. This material was aspirated with the help of an endoscopic ultrasonic aspirator. The outcome was favorable, with a resolution of infection and re-implantation of the ventriculo-peritoneal shunt. Surprisingly, post-operative radiological examination showed substantial modification of the anatomy of the posterior fossa with disappearing of the Dandy-Walker cyst. To the best of our knowledge, this is the first documented report of a true Dandy-Walker malformation that modified its anatomical appearance over time. DISCUSSION AND CONCLUSION: Endoscopic aspiration of intracranial purulent collection should be considered a valid option to manage complicated cases. An endoscopic ultrasonic aspirator may make the procedure more effective and faster.

Refining the Neuroimaging Definition of the Dandy-Walker Phenotype.

BACKGROUND AND PURPOSE: The traditionally described Dandy-Walker malformation comprises a range of cerebellar and posterior fossa abnormalities with variable clinical severity. We aimed to establish updated imaging criteria for Dandy-Walker malformation on the basis of cerebellar development. MATERIALS AND METHODS: In this multicenter study, retrospective MR imaging examinations from fetuses and children previously diagnosed with Dandy-Walker malformation or vermian hypoplasia were re-evaluated, using the choroid plexus/tela choroidea location and the fastigial recess shape to differentiate Dandy-Walker malformation from vermian hypoplasia. Multiple additional measures of the posterior fossa and cerebellum were also obtained and compared between Dandy-Walker malformation and other diagnoses. RESULTS: Four hundred forty-six examinations were analyzed (174 fetal and 272 postnatal). The most common diagnoses were Dandy-Walker malformation (78%), vermian hypoplasia (14%), vermian hypoplasia with Blake pouch cyst (9%), and Blake pouch cyst (4%). Most measures were significant differentiators of Dandy-Walker malformation from non-Dandy-Walker malformation both pre- and postnatally (P < .01); the tegmentovermian and fastigial recess angles were the most significant quantitative measures. Posterior fossa perimeter and vascular injury evidence were not significant differentiators pre- or postnatally (P > .3). The superior posterior fossa angle, torcular location, and vermian height differentiated groups postnatally (P < .01), but not prenatally (P > .07). CONCLUSIONS: As confirmed by objective measures, the modern Dandy-Walker malformation phenotype is best defined by inferior predominant vermian hypoplasia, an enlarged tegmentovermian angle, inferolateral displacement of the tela choroidea/choroid plexus, an obtuse fastigial recess, and an unpaired caudal lobule. Posterior fossa size and torcular location should be eliminated from the diagnostic criteria. This refined phenotype may help guide future study of the numerous etiologies and varied clinical outcomes.

Occipital encephalocele associated with Dandy-Walker malformation: a case-based review.

INTRODUCTION: Occipital encephalocele is a brain malformation that has been remotely associated with Dandy-Walker; only case reports and very small series have been published so far; therefore, their behavior and management are still under investigation. The goal of the present case-based review is to provide a summary of the state of the art in this association. METHODS AND RESULTS: The pertinent literature has been reviewed, and an exemplary case has been reported (an 11-month-old female with Dandy-Walker malformation and occipital encephalocele). So far, 33 cases have been described, with a mean age at surgery of 5, 1 day). The majority of the cases tend to present with hydrocephalus. There are no specific surgery approaches or global consensus about this association. The management possibly relies on surgery with shunt or encephalocele excision but without a dedicated protocol yet. CONCLUSIONS: The clinical research on occipital encephalocele in association with Dandy-Walker malformation is just at the beginning. New targets and wide-ranging clinical trials are needed to get an optimal management protocol.

Regional brain development in fetuses with Dandy-Walker malformation: A volumetric fetal brain magnetic resonance imaging study.

Dandy-Walker malformation (DWM) is a common prenatally diagnosed cerebellar malformation, characterized by cystic dilatation of the fourth ventricle, upward rotation of the hypoplastic vermis, and posterior fossa enlargement with torcular elevation. DWM is associated with a broad spectrum of neurodevelopmental abnormalities such as cognitive, motor, and behavioral impairments, which cannot be explained solely by cerebellar malformations. Notably, the pathogenesis of these symptoms remains poorly understood. This study investigated whether fetal structural developmental abnormalities in DWM extended beyond the posterior fossa to the cerebrum even in fetuses without apparent cerebral anomalies. Post-acquisition volumetric fetal magnetic resonance imaging (MRI) analysis was performed in 12 fetuses with DWM and 14 control fetuses. Growth trajectories of the volumes of the cortical plate, subcortical parenchyma, cerebellar hemispheres, and vermis between 18 and 33 weeks of gestation were compared. The median (interquartile range) gestational ages at the time of MRI were 22.4 (19.4-24.0) and 23.9 (20.6-29.2) weeks in the DWM and control groups, respectively (p = 0.269). Eight of the 12 fetuses with DWM presented with associated cerebral anomalies, including hydrocephalus (n = 3), cerebral ventriculomegaly (n = 3), and complete (n = 2) and partial (n = 2) agenesis of the corpus callosum (ACC); 7 presented with extracerebral abnormalities. Chromosomal abnormalities were detected by microarray analysis in 4 of 11 fetuses with DWM, using amniocentesis. Volumetric analysis revealed that the cortical plate was significantly larger in fetuses with DWM than in controls (p = 0.040). Even without ACC, the subcortical parenchyma, whole cerebrum, cerebellar hemispheres, and whole brain were significantly larger in fetuses with DWM (n = 8) than in controls (p = 0.004, 0.025, 0.033, and 0.026, respectively). In conclusion, volumetric fetal MRI analysis demonstrated that the development of DWM extends throughout the brain during the fetal period, even without apparent cerebral anomalies.

Management and Outcome of a Neurologically Intact Infant with Pierre Robin Sequence and Dandy-Walker Variant Diagnosed with Large Hemispheric Brain Abscess ­ Case Report

Pierre Robin sequence (PRS) is a condition consisting of three essential components: micrognathia or retrognathia, cleft palate, and glossoptosis. It can be part of multiple congenital anomalies. We present the case and outcome of a 3-month-old clinically stable patient who has PRS with Dandy-Walker variant ­ which is a rare presentation in the literature ­ with a large right hemispheric brain abscess, treated with multiple minimally-invasive surgical drainage procedures with adjuvant antibiotics.

Short- and Long-Term Outcomes of Prenatally Diagnosed Dandy-Walker Malformation, Vermian Hypoplasia, and Blake Pouch Cyst.

Dandy-Walker continuum, which includes Dandy-Walker malformation, vermian hypoplasia, and Blake pouch cyst, is among the most commonly diagnosed posterior fossa malformation by fetal magnetic resonance imaging (MRI). The objective of our retrospective study was to evaluate fetal and postnatal MRI scan and clinical outcomes. Seventy-two patients were identified; 40 patients had postnatal imaging and follow-up (7 Dandy-Walker malformation, 26 vermian hypoplasia, and 7 Blake pouch cyst). Although all patients with Dandy-Walker malformation required ventriculoperitoneal shunts and 66% were intubated at birth, none required tracheostomy tube and 2 of 5 surviving children had no neurologic deficits. Vermian hypoplasia was strongly associated with genetic conditions and cardiac malformations; odds of not ambulating normally were 12 times greater if a syndrome or injury was present. Echocardiogram and genetic screening are recommended with vermian hypoplasia. There is a risk for epilepsy in both Dandy-Walker malformation and vermian hypoplasia. Blake pouch cyst can be complicated by hydrocephalus, but outcome is favorable.

Position of the choroid plexus of the fourth ventricle in first- and second-trimester fetuses: a novel approach to early diagnosis of cystic posterior fossa anomalies.

OBJECTIVE: To describe the sonographic appearance and position of the choroid plexus of the fourth ventricle (4V-CP) between 12 and 21 weeks' gestation in normal fetuses and in fetuses with Dandy-Walker malformation (DWM) or Blake's pouch cyst (BPC). METHODS: The study population comprised 90 prospectively recruited normal singleton pregnancies and 41 pregnancies identified retrospectively from our institutional database that had a suspected posterior fossa anomaly at 12-13 weeks' gestation based on the ultrasound finding of abnormal hindbrain spaces. In all cases the final diagnosis was confirmed by prenatal and/or postnatal magnetic resonance imaging or postmortem examination. All pregnancies underwent a detailed ultrasound assessment, including a dedicated examination of the posterior fossa, at 12-13 weeks, 15-16 weeks and 20-21 weeks of gestation. Two-dimensional ultrasound images of the midsagittal and coronal views of the brain through the posterior fontanelle and three-dimensional volume datasets were obtained. Multiplanar orthogonal image correlation with volume contrast imaging was used as the reference visualization mode. Two independent operators, blinded to the fetal outcome, were asked to classify the 4V-CP as visible or not visible in both normal and abnormal cases, and to assess if the 4V-CP was positioned inside or outside the cyst in fetuses with DWM and BPC. RESULTS: Of the 41 fetuses with apparently isolated cystic posterior fossa anomaly in the first trimester, eight were diagnosed with DWM, 29 were diagnosed with BPC and four were found to be normal in the second trimester. The position of the 4V-CP differed between DWM, BPC and normal cases in the first- and second-trimester ultrasound examinations. In particular, in normal fetuses, no cyst was present and, in the midsagittal and coronal planes of the posterior fossa, the 4V-CP appeared as an echogenic oval-shaped structure located inside the 4V apparently attached to the cerebellar vermis. In fetuses with DWM, the 4V-CP was not visible in the midsagittal view because it was displaced inferolaterally by the cyst. In contrast, in the coronal view of the posterior brain, the 4V-CP was visualized in all cases with DWM at 12-13 weeks, with a moderate decrease in the visualization rate at 15-16 weeks (87.5%) and at 20-21 weeks (75%). In the coronal view, the 4V-CP was classified as being outside the cyst in all DWM cases at 12-13 weeks and in 87.5% and 75% of cases at 15-16 and 20-21 weeks, respectively. In fetuses with BPC, the 4V-CP was visualized in all cases in both the midsagittal and coronal views at 12-13 weeks and in 100% and 96.6% of cases, respectively, at 15-16 weeks. In the coronal view, the 4V-CP was classified as being inside the cyst in 28 (96.6%), 27 (93.1%) and 25 (86.2%) cases at 12-13, 15-16 and 20-21 weeks, respectively. The medial segment of the 4V-CP was visualized near the inferior part of the vermis. CONCLUSIONS: Our study shows that longitudinal ultrasound assessment of the 4V-CP and its temporal changes from 12 to 21 weeks is feasible. The 4V-CP is located inside the cyst, just below the vermis, in BPC and outside the cyst, inferolaterally displaced and distant from the vermian margin, in DWM, consistent with the pathogenesis of the two conditions. The position of the 4V-CP is a useful sonographic marker that can help differentiate between DWM and BPC as early as in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Taenia-tela choroidea complex and choroid plexus location help distinguish Dandy-Walker malformation and Blake pouch cysts.

BACKGROUND: Dandy-Walker malformation and Blake pouch cysts can have overlapping imaging features. The choroid plexus and associated taenia-tela choroidea complex are displaced inferolaterally in Dandy-Walker malformation and below the vermis in Blake pouch cysts. OBJECTIVE: To determine the normal fetal and postnatal MR appearance of the choroid plexus and taenia-tela choroidea complex, and whether their location can help distinguish Dandy-Walker malformation from Blake pouch cysts. MATERIALS AND METHODS: In this retrospective study, we evaluated brain MR exams from normal-appearing fetuses (gestational age 19-38 weeks) and infants, fetal and postnatal exams in Blake pouch cysts and Dandy-Walker malformation, and ambiguous cases equivocal for mild Dandy-Walker malformation and Blake pouch cysts. We documented choroid plexus and the taenia-tela choroidea complex location and axial and sagittal angles in each case. Then we contrasted and compared the original and updated fetal diagnoses based on taenia-tela choroidea complex and choroid plexus positions. RESULTS: The choroid plexus location and the taenia-tela choroidea complex location and angles varied significantly among normal exams, Blake pouch cyst exams and Dandy-Walker malformation exams (P<0.01). Dandy-Walker malformation showed inferolateral displacement of the taenia-tela choroidea complex and choroid plexus distant from the vermis. Adding the taenia-tela choroidea complex and choroid plexus into the assessment improved diagnostic accuracy, especially in ambiguous cases. CONCLUSION: The location of the taenia-tela choroidea complex and choroid plexus provided additional diagnostic neuroimaging clues that could be used in conjunction with other conventional findings to distinguish Dandy-Walker malformation and Blake pouch cysts. Normal, Blake pouch cyst, and Dandy-Walker malformation cases differed with regard to taenia-tela choroidea complex and choroid plexus position. Inferolateral taenia-tela choroidea complex displacement distant from the vermian margin was characteristic of Dandy-Walker malformation.

A rare mutant of OFD1 gene responsible for Joubert syndrome with significant phenotype variation.

Joubert syndrome (JBTS), a rare genetic disorder resulted from primary cilium defects or basal-body dysfunction, is characterized by agenesis of cerebellar vermis and abnormal brain stem. Both genotypes and phenotypes of JBTS are highly heterogeneous. The identification of pathogenic gene variation is essential for making a definite diagnosis on JBTS. Here, we found that hypoplasia of cerebellar vermis occurred in three male members in a Chinese family. Then, we performed whole exome sequencing to identify a novel missense mutation c.599T > C (p. L200P) in the OFD1 gene which is the candidate gene of X-linked JBTS (JBST10). The following analysis showed that the variant was absent in the 1000 Genomes, ExAC and the 200 female controls; the position 200 Leucine residue was highly conserved across species; the missense variant was predicted to be deleterious using PolyPhen-2, PROVEAN, SIFT and Mutation Taster. The OFD1 expression was heavily lower in the proband and an induced male fetus compared with a healthy male with a wild-type OFD1 gene. The in vitro expression analysis of transiently transfecting c.599T or c.599C plasmids into HEK-293T cells confirmed that the missense mutation caused OFD1 reduction at the protein level. And further the mutated OFD1 decreased the level of Gli1 protein, a read-out of Sonic hedgehog (SHH) signaling essential for development of central neural system. A known pathogenic variant c.515T > C (p. L172P) showed the similar results. All of these observations suggested that the missense mutation causes the loss function of OFD1, resulting in SHH signaling impairs and brain development abnormality. In addition, the three patients have Dandy-Walker malformation, macrogyria and tetralogy of Fallot, respectively, the latter two of which are firstly found in JBTS10 patients. In conclusion, our findings expand the context of genotype and phenotype in the JBTS10 patients.