 Hello everyone, myself Dr. Arfi, a third-year resident going to present my case series on a genetic disorder that is Jobert's syndrome. Aim of my paper will be to study a rare genetic disorder for its various clinical presentation to discuss its variable phenotypic presentation and radiological pattern and also to see if there is a correlation between severity of symptoms and the radiological findings. Introduction. Jobert's syndrome is a rare genetic heterogeneously inherited disorder named after Marie Jobert in 1969. It is characterized by brain stem and cerebellar malformation and multi-systemic affection involving nervous, ocular, gastrointestinal and urogenital system in varying proportion. It belongs to a primedicellular disease, primedicellular, which are, which are immotile celia, helps in receiving and transmitting signals. They play an important role in growth and function of the neuronal cells, skeleton, retina photoreceptors, kidney tubules and collecting ducts and also liver. Jobert's syndrome, here I would also like to discuss that celia related disorders are mainly categorized into motile celopathies such as catagener syndrome, which most of us are aware about and immotile celopathies that we might not have heard much about and these includes Jobert's syndrome, nephronyptasis, Beedle-Burtard syndrome and Meckel's syndrome. Jobert's syndrome and other immotile celopathies show pleotropy and overlapping phenotypes. The term Jobert's syndrome related disorder has been adopted to describe various pathological entities with the neuro radiological feature of mola to sign while involving other organs as well. Here in this presentation, we would discuss two cases in a family and both of them having similar complaints but with different severity. Family history revealed second-degree concern to universe marriage. No other prime members in the family were affected. My first case is a six-year-old child who was brought to OPD in the Department of Pediatrics, Jawaharlal Nehru Medical College for evaluation of developmental delay. According to her mother, she could not sit, stand or speak. However, there is spontaneous cry and smile. She also has gaze instability. There is no history of any abnormal facial-like movements. Further questioning to the patient's mother also revealed that she had weak cry since birth which rose the suspicion of some abnormality. NCCT head was also performed at the age of six months which came out to be normal. Currently, she has poor and delayed developmental milestones. She is not able to stand or sit on her own or with support. She was delivered by an uncomplicated caesarean at nine months of period for indication was laid for gestational age. She did not cry at the time of her birth. The postnatal history was negative for any prolonged admission at neonatal ICU. On examining the child, she appeared thin and fragile. She could not stand or sit. Mild facial dysmorphia was noted with a depressed nasal bridge and deepened orbital sockets. She is unable to follow command and does not follow her gaze on specific object. Ocular examination revealed bilateral horizontal pendulum stagmus without myopia. The cardiovascular examination was normal. A pulmonary examination revealed a prominent excretory visa without just in drawing. Examination finding of the cranial nerves were also normal. Motor examination revealed hypotonia with normal tendon reflexes. After examining the child, she was advised by the clinician to undergo MRI brain. As CT head at the age of six months came out to be normal and this is the MRI brain of the child where in the first two images, the axial and the coronal images, we can see that there is a genesis of the cerebellar vermice and there is deep and interpredicular fossa. For the curds at the level of midbrain and cerebellum shows thickened abnormally horizontally placed superior cerebellar peduncles giving the molar tooth sign. The appearance of the fourth ventricle gave the batwing appearance also called as umbrella sign. Here I would also like to discuss other signs such as buttock sign which is also described for jobbers syndrome and coronal image where there is a midline cleft scene separating the two cerebellar hemispheres due to absent cerebellar vermice. Other signs such as shepherd crook sign is also described in such vital views of the posterior fossa where the brain stem and ponds makes the shaft of the crook and abnormal superior cerebellar peduncles and cerebellar hemispheres make the arc of the crook. In my fifth image, sagittal T1-vitted image, there is thinning of the posterior body and spleenium of the corpus chelosum which was an additional finding. My second case is a three-year-old boy with the same symptoms and signs as his sister with different severity. He has developmental delay however less severe than his sister. He could sit or stand with support. He also had gaze abnormality. He could speak by syllables. No history of Cicerolec activity was there. Birth is to reveal that he was delivered by Cesarean at the age of nine months. Indication was caught around the neck with meconium aspiration. He weighed approximately 2.4 kg. He didn't cry immediately after birth and was on ventilator for 24 hours. Neurological examinations were normal. Rest of the findings were also normal. After his sister was diagnosed with jobbers syndrome and looking after his sign and symptoms, he was also advised MRI brain and it was very striking that the features were similar to his sister's sisters. Here in the first two images, we can see that there is a genesis of the cerebellar hemisphere. As we have seen in our first case, there is deep intubidumcular fossa. Molar tooth sign is also appreciated. However, umbrella sign was not seen. In the sagittal image, the corpus callosum appeared to be normal for his age. Coming to the discussion part, jobbers syndrome is a rare disorder of central nervous system with the incidence of one per one lakh children. Only few cases have been reported till now worldwide and by 2009, approximately 200 cases have been reported. Both sporadic and autosomal recessive pattern of inheritance has been described. Dr. Mary Jobert and co-workers in 1969 for the first time described four siblings with a texia, cognitive impairment, eye movement abnormalities, cerebellar vermice genesis, and episodic tachypnea in a French Canadian family. Marriott R in 1997 described this mid-brain hindbrain malformation on MRI as a result of hyperplasia of the midline cerebellar vermice resembling the cross-section of a molar tooth appearance, which is pathognomic for Jobert syndrome. In the same year, it was reported that there is association between Jobert syndrome and renal cystic disorders and liver fibrosis. But in our cases, it did not have any organ disorders and their ultrasonography and laboratory findings were normal. The first report and subsequent reports have been determined that Jobert syndrome has autosomal recessive inheritance and mutations in the eight ciliary basal body genes. So far, more than 30 causative genes have been found for the various subtypes of Jobert syndrome-related disorders. Backman Gekescu et al. reported TMEM67, C5ORF42, CC2D2A, CAP290, and AHI1 gene, which were more frequently found. The AHI1 gene, which is found in 10 to 15 percent of the patients, and CAP290 is found in 10 percent of the cases, and are the most common mutant gene related to Jobert syndrome-related disorders. AHI1 is abundant in brain and kidney and weakly expressed in the liver as well. The clinical features of Jobert syndrome-related disorders vary from being mild to severe, and it typically presents with the following features, such as abnormal popular findings, for example, nystagmus, strabismus, poses, hypotonia, and edexia, leading to gate abnormalities, respiratory dysregulation in the form of hyperepnea apnea episodes, which are usually present at the time of neonatal period and gradually diminishes, developmental retardation going to the abnormality of cerebellum and brainstem, and typical dysmorphic features such as hypertelurism, broad forehead, broad mouth with protrusion of tongue, or ptosis. The triad of Jobert syndrome includes hypotonia, developmental delay, and brainstem, cerebellum malformation, giving the molar tooth sign. Based on, as we have discussed, that imotile seropathies can involve multiple organs. So, based on the organ involved, Transisco etyl classified Jobert syndrome related disorders into six phenotypes. This includes pure Jobert syndrome with multiple organ involvement, Jobert syndrome with renal defect, Jobert syndrome with ocular defect, with ocular renal defects, Jobert syndrome with hepatic defects, and with orophatio-digital defects. The radiographic features include the molar tooth sign and the batwing configuration, which are the classical imaging findings. Severe hypogenesis to complete agenesis of the cerebellar hemisphere is characteristic. The superior cerebellar peduncles are thickened and have abnormal horizontal force. The lack of peduncular deputicization, which can be assessed by diffusion tensor imaging, often results in a superior vermin cleft. There can be distorted and superiorly pointing cerebellar white matter trap, especially in the posterior cerebellum. Other abnormalities could be inferior or abnormal inferior olivary nucleus, and a separate entoreal abnormalities include cortical dysplasia, corpus callosum abnormalities, as we have seen in our first case, heterotopic gray matter, and incafelocene. In coming to our case scenario, our first case was a six-year-old girl with severe developmental delay. In addition to molar tooth appearance, there was batwing appearance of the fourth ventricle with thinning of the corpus callosum. However, in our second case, with mild symptoms and malart tooth appearance, the corpus callosum appeared normal, and there was no batwing configuration. So, we have made a hypothesis that there is a possible correlation between severity of symptoms and radiological findings. However, there is limitation, as it is statistically insignificant. Further studies with more number of cases could be performed to prove this correlation statistically relevant. So, is the disease prenatally diagnosable? So, the answer is yes, it can be diagnosed with but with uncertainty. Diagnosis of Gerber syndrome is commonly made after birth. However, fewer cases of prenatal diagnosis by USG have been made, and they are more likely to be misdirected because of some nonspecific features that also manifest dandy woken malformation and cerebellum, cranioserebellum, cardiac syndrome, and many other diseases. Zool et al. in prenatal head sonography found absent for cerebellar vermice with fourth ventricle, communicating with the posterior fossa, molar tooth sign was also seen with enlarged fourth ventricle. Prenatal MRI in the same patient was done and molar tooth sign was seen with dilated cisterna magna and enlarged fourth ventricle. But the average age at diagnosis of Gerber syndrome is 33 months and therefore it should be considered a syndrome with varying phenotype, and it makes it difficult to diagnose the accurate subtype during the newborn period. However, we can get some clue for some abnormality in the brain. In highly suspected patients. Coming to the management part, in general, the prognosis of Gerber syndrome is poor. It largely depends on severity of different organ systems. Stylian et al. described variable course in these patients. Some patients die early in the infancy. Some have severe developmental handicaps and others survive with mild developmental delay. A five-year survival rate is 50% and death is usually due to defeating difficulties and respiratory infections. Treatment options are not readily available as this disease onset is during the ingestation period. Rehabilitation is the main state of management for these patients. Symptomatic and supportive therapy in the form of physiotherapy and speech therapy could help. Optimal management needs multidisciplinary approach, special consideration to respiratory and feeding disorders, cognitive and behavioral evaluation also could be helpful to these young children. Rehabilitation, therapy can improve disabilities of patients with Gerber syndrome. Gene analysis is the cornerstone of the disease. However, in our case, the poor financial status of the patient, genetic study could not be performed. Learned the genetic counseling and its prevention. Genetic counseling is important for its prevention as it is an autosomal recessive condition. The counseling should include that there is a recurrence rate of 25%. That is, there are 25% chances of having an affected child and 75% chances of having a phenotypically normal child, among which 50% will be carrier. And therefore, concern bonus marriage in the future among their children should be prohibited. So I would like to conclude my presentation with the following conclusion that Gerber syndrome is a rare disorder of central nervous system with variable clinical presentation. The classic imaging findings include molar tooth sign, which is pathognomic of Gerber syndrome and a batting configuration of the fourth ventricle, which could be seen both in CT and MRI. In our two cases, there's a positive correlation between severity of symptoms and neurological findings. However, many more studies need to be done to prove it statistically relevant. These are the references of my paper. Thank you.