Joubert Syndrome with Orofaciodigital Defects

Joubert Syndrome with Orofaciodigital Defects A report of Joubert syndrome in an infant, with literature review ABSTRACT Joubert Syndrome and related disorders (JSRD) are a group of rare autosomal recessive disorders with a hallmark molar tooth sign (MTS) visible on axial magnetic resonance images of the brain. Joubert syndrome with Oro-facial-digital defects (JS-OFD) represents a rare subtype of JSRD. This syndrome is often difficult to diagnose because of its wide range of genotypic-phenotypic variations. Despite its profound oro-facial manifestations, dental literature describing the syndrome is scarce. This is a case report of an 8-year-old boy who reported to the out-patient department of pediatric dentistry with the chief complaint of abnormal front teeth. The child exhibited facial dysmorphism, strabismus, polydactyly of hands and feet along with oro-dental features of a high arched palate and high lingual frenum attachment. MRI report stated the presence of molar tooth sign. Key Words: Joubert syndrome and related disorders, Oro-facial-digital syndrome type VI, molar tooth sign INTRODUCTION Joubert syndrome (JS) was first described by Marie Joubert in 1968 in four siblings with agenesis of the cerebellar vermis who presented with episodic hyperpnoea, abnormal eye movements, ataxia and intellectual disability [1,2]. Several years later, it was discovered that JS results from maldevelopment of the midbrain and cerebellar vermis, producing a pathognomonic MTS on MRI [3]. The common term Joubert Syndrome and Related Disorders (JSRD) was then coined for the group of conditions presenting with the MTS [4]. The incidence of this clinical entity has not been precisely determined, however, it may range between 1/80,000 and 1/100,000 live births [2] with only about 200 cases that have been reported worldwide[5]. CASE REPORT An 8 year old boy reported to the outpatient Department of Pedodontics and Preventive Dentistry at the Faculty of Dental Sciences, M.S. Ramaiah University of Applied Sciences, Bangalore for the evaluation of abnormal front teeth. History revealed that he was a second child of a second degree consanguineous marriage. Figure I is the pedigree chart depicting the patient’s family history. The mother reported delayed attainment of developmental milestones and the child being a â€Å"slow-learner†. On intra-oral examination, the child was in the early mixed dentition stage; the teeth present were first permanent molars, permanent mandibular central incisors, erupting maxillary permanent central incisors , primary left central incisor, primary canines of all the quadrants, primary mandibular lateral incisors and first and second primary molars of all the quadrants. The crown of the primary left central incisor (61) was conical in shape and a developing anterior cross-bite was noticed due to palatally erupting 11 and 21. A high-arched palate and high lingual frenum attachment were also seen. Extra-orally, the patient exhibited facial dysmorphism in form of depressed nasal bridge, broad nasal tip, upper lip notch and his upper lip was short compared to the broad and thick lower lip. Prominent bilateral epicanthal folds, widely spaced eyes (hypertelorism) and a unilateral squint (strabismus) of the right eye were profound facial characteristics. His cranial morphology and hair were apparently normal. Bilateral post-axial polydactyly of both the hands and feet were noticed. The remainder of the systemic evaluation was insignificant. However, the patient showed poor muscular control due to delayed gross as well as fine motor development. On review of the patient’s medical records, it was seen that the possibility of Joubert Syndrome was considered on detection of inferior vermian agenesis and polydactyly on antenatal ultrasonography performed at 28 weeks of intra-uterine life. Eye movements and respiration were reviewed and found to be normal. Foetal MRI was done at another medical center and they considered the possibility of Dandy-Walker anomaly. At 5 months of age, neurologic evaluation was conducted and nystagmus along with very brisk deep tendon reflexes (DTRs 3+ category) was noticed; following which, magnetic resonance imaging (MRI) of the brain was advised. The MRI reports indicated complete agenesis of the cerebellar vermis which resulted in median approach of the two cerebellar hemispheres. Superior cerebellar peduncles appeared thin and distinctly defined across the pontomesencephalic cisterns giving the characteristic â€Å"molar tooth sign†. Also the 4th ventricle was slightly dilated and h ad assumed a â€Å"bat-wing† appearance. Inspite of the all the MRI findings being suggestive of â€Å"Joubert sydrome†, neither was any definitive diagnosis made nor any neurological follow-up maintained. With respect to dental treatment rendered, the patient was found to be lacking cooperative ability, but keeping in mind the extreme sensitivity to the respiratory depressant effects of anesthetic agents, sedation and GA was ruled out. Considering this inability, after extraction of his primary central incisor (61), a lower inclined plane appliance was planned to correct the developing cross-bite. Patient did not cooperate for fabrication of a fixed appliance. Upper and lower primary impressions were made, a removable lower inclined plane appliance with Adams clasps on 75 and 85 was fabricated and delivered to the patient. However, the patient showed poor compliance with the appliance and refused to wear it beyond the third day. Following this, we considered the correction of the cross-bite by constructing a bonded resin-composite inclined plane [6, 7]. The labial surface of the mandibular incisors was etched with 37% phosphoric acid (Scotchbondâ„ ¢ Multi-purpose Etchant, 3M, USA) for 15 seconds, rinsed and dried. An adhesive system (Adperâ„ ¢ Single Bond 2, 3M, USA) was applied and cured for 20s using a visible light cure unit (_______). Composite resin (Filtekâ„ ¢ Z350XT, 3M, USA) was formed into an inclined block 45 degree to the longitudinal axis of the teeth. The height was adjusted so as to maintain the only contact between both arches at the level of these incisors. The inclined plane was polished using a polishing disc. The child was motivated to maintain good oral hygiene and the parents were instructed regarding the maintenance of a soft diet. The child was recalled after 1 day and then 1 week to clinically evaluate the treatment progress. At 1 week interval, edge-to-edge bite was achieved while complete correction of the crossbite took place in 2 weeks. Following this, the composite inclined plane was removed using a diamond point at low speed, the enamel surface was polished and topical fluoride application was done. The child is under regul ar follow-up at our hospital. DISCUSSION The spectrum of Joubert Syndrome and Related Disorders (JSRD) comprises all disorders presenting the molar tooth sign (MTS) on brain imaging. JSRD include Joubert syndrome [OMIM#213300], along with any related condition(s) presenting with the MTS, like Varadi-Papp syndrome (or Orofaciodigital type VI, [OMIM%277170]), COACH syndrome [OMIM#216360], Dekaban-Arima syndrome [OMIM%243910], Malta syndrome and a few cases with Senior- Loken syndrome [OMIM#266900]. Till date no major gene has been consistently associated with Oro-facio-digital Syndrome type VI (OFD VI) however, mutations in the TMEM216 gene are known to be seen occasionally[]. All JSRD genes isolated so far, encode for proteins of the primary cilium and thus these disorders fall in the â€Å"ciliopathies† group of disorders [9]. Previously in literature, JS-OFD has also been referred to as Oro-facio-digital Syndrome type VI (OFD VI) or Varadi-Papp Syndrome [10, 11,12]. However, recently, Brancati et al. have discouraged the continued use of such eponyms in favor of a more practical, clinical-genetic classification. They have proposed a classification of JSRDs into six subgroups based on the main organ(s) involvement and the established genotype-phenotype correlates [2]. They classified JSRDs into: Pure JS JS with ocular defect (JS-O) JS with renal defect (JS-R) JS with oculorenal defects (JS-OR) JS with hepatic defect (JS-H) JS with oro-facio-digital defects (JS-OFD) . A diagnosis of JSRD should be suspected in all infants presenting with hypotonia, abnormal eye movements (in particular oculomotor apraxia, but also nystagmus) and developmental delay. The occurrence of abnormalities in the respiratory pattern, i.e. hyperpneas alternating with periods of apnea, reinforces the clinical suspicion of the disease. In these children, a brain MRI is sufficient to confirm or exclude the diagnosis, based on the detection of the MTS. Once a diagnosis of JSRD has been made, children should enter a diagnostic protocol to assess the possible multiorgan involvement[2]. Presence of MTS is considered pathognomic for diagnosis of JS-OFD (or OFD VI). MTS is characterized by presence of a hypoplastic or completely absent cerebellar vermis, which is indicated by the hallmark â€Å"Molar Tooth Sign† found on axial view of brain MRI scan. MTS has not been described in any other type of oro-facial-digital syndrome and its presence allows differentiation of OFD VI from other types [9]. In addition, several other oral, dental and digital malformations are typical of JS-OFD. These have been enlisted in Table I. Recently, Poretti et al. [9] have suggested a diagnostic criterion for OFD VI. The criterion being MTS and one or more of the following: tongue hamartoma(s) and/or additional frenula and/or upper lip notch; mesoaxial polydactyly of one or more hands or feet; hypothalamic hamartoma. These criteria allow the diagnosis to be made even in the absence of oral findings and/or polydactyly. The validity of these criteria needs to be reassessed in additional cohorts of patients and after the identification of major genetic determinants of OFD VI. Along with presence of the pathognomic MTS, our patient showed bilateral postaxial polydactyly of hands and feet. Mesoaxial hand polydactyly is extremely rare and specific for OFD VI among the JSRD phenotypes, but not consistent in OFD VI because different forms of polydactyly have been previously reported [13,14,15,16]. Moreover, it is to be noted that the syndrome is known to show a high degree of genotypic-phenotypic variations and it’s often difficult to arrive at a conclusive diagnosis. Thus, it can be said that the reported case probably represents variability within OFD VI. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings [9]. Steinlinet al. [17] suggested that outcomes in JS can be divided into three courses: first, children who die young; second, patients who survive but have severe developmental delay with the development quotient (DQ) being less than 30 along with a variety of visual and motor handicaps; and third, patients whose developmental quotients fall within the mildly delayed range (60-85). A remarkable finding in the case reported was, the level of cognitive development; with intelligence quotient (IQ) being 90 which falls in the â€Å"average† IQ range according to the Stanford-Binet Intelligence Scale: Fifth Edition (SB5)[18]. So far, normal cognitive functions (without formal IQ assessment) have only been reported in one patient, attending a regular school [ 19]. Despite the fact that Joubert syndrome is very rare in India, an early diagnosis is necessary for genetic counseling and treatment planning. Treatment is mainly symptomatic and includes possible medico-surgical supportive interventions. Also, the diagnosis is important for future procedures that require anesthesia. Of particular caution is that these patients are sensitive to respiratory depressant effects of anesthetic agents like opiates and nitrous oxide. Hence, anesthesia using inhalational induction, controlled ventilation, avoidance of opioids, and close postoperative monitoring is recommended 20]. The prognosis is almost always poor, leading to early death and those who survive usually require supportive care throughout life. Annual evaluation of the growth status, vision and general wellness is recommended. Periodic neuropsychological follow-up should be maintained. REFERENCES Joubert M, Eisenring JJ, Andermann F: Familial dysgenesis of the vermis: a syndrome of hyperventilation, abnormal eye movements and retardation. Neurology 1968, 18:302-303. Brancati F, Dallapiccola B, Valente EM. jJoubert Syndrome and related disorders. Orphanet J Rar Diseases 2010 5:20. Maria BL, Hoang KB, Tusa RJ, Mancuso AA, Hamed LM, Quisling RG, Hove MT, Fennell EB, Booth-Jones M, Ringdahl DM, Yachnis AT, Creel G, Frerking B: Joubert syndrome revisited: key ocular motor signs with magnetic resonance imaging correlation. J Child Neurol 1997, 12:423-430. Gleeson, J. G., Keeler, L. C., Parisi, M. A., Marsh, S. E., Chance, P. F., Glass, I. A., Graham Jr, J. M., Maria, B. L., Barkovich, A. J. and Dobyns, W. B.. Molar toothsign of the midbrain–hindbrain junction: Occurrence in multiple distinct syndromes. Am J Med Genet 2004, 125A:125–134. Choh SA, Choh NA, Bhat SA, Jehangir M. MRI findings in Joubert syndrome.Indian J Pediatr.2009; 76:231–5. Bayrak S, Tunc ES. Treatment of Anterior Dental Crossbite Using Bonded Resin-Composite Slopes: Case Reports. Eur J Dent 2008; 2:303-307. Sari S,Gokalp H,Aras S. Correction of anterior dental crossbite with composite as an inclined plane. Int J Paediatr Dent2001 May; 11(3):201-8. Edvardson S,Shaag A,Zenvirt S,Erlich Y,Hannon GJ,Shanske AL,Gomori JM,Ekstein J,Elpeleg O. Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation. Am J Hum Genet. Jan 8, 2010; 86(1): 93–97 Poretti A, Vitiello G, Hennekam RCM, Arrigoni F, Bertini E, Borgatti R, Brancati F, D’Arrigo S, Faravelli F, Giordano L, Huisman TAGM, Iannicelli M, Kluger G, Kyllerman M, Landgren M, Lees MM, Pinelli L, Romaniello R, Scheer I, Schwarz CE, Spiegel R, Tibussek D, Valente EM, Boltshauser E. Delineation and Diagnostic Criteria of Oral-Facial-Digital Syndrome Type VI. Orphanet J Rar Diseases 2012, 7:4. 10. Patra S ,Purkait R,Samanta T,Bhadra R. Varadi Papp syndrome, an unusual variant of oral-facial-digital syndrome: Report of a rare case. Ann Indian Acad Neurol. 2013 Apr-Jun; 16(2): 289–291. Z Adà ¡m, Z Papp Prenatal diagnosis of orofaciodigital syndrome Varadi-Papp type.JUMOctober 199615:714. Atahan Guven, M., Ceylaner, S., Prefumo, F. and Uzel, M. (2004), Prenatal sonographic findings in a case of Varadi–Papp syndrome. Prenat Diagn, 24:989–991. Rabah M. Shawky,Heba Salah Abd-Elkhalek Elabd,Shaimaa Gad,Radwa Gamal,Shaimaa Abdelsattar Mohammad. Oral–Facial–Digital Syndrome type VI with self mutilations, Egypt J Med Hum Genet (2014), http://dx.doi.org/10.1016/j.ejmhg.2014.05.006 Mauceri L, Greco F, Baieli S, Sorge G. Varadi-Papp syndrome: report of a case. Clin Dysmorphol 2000; 9:289–90. Al-Gazali LI, Sztriha L, Punnose J, Shather W, Nork M. Absent pituitary gland and hypoplasia of the cerebellar vermis associated with partial ophthalmoplegia and postaxial polydactyly: a variant of orofaciodigital syndrome VI or a new syndrome? J Med Genet 1999; 36:161–6. Haug K, Khan S, Fuchs S, Ko ¨ nig R. OFD II, OFD VI, and Joubert syndrome manifestations in 2 sibs. Am J Med Genet 2000; 91:135–7. Steinlin M, Schmid M, Landau K, Boltshauser E. Follow-up in children with Joubert syndrome. Neuropediatrics 1997, 28(4): 204-11. Kaufman, Alan S.IQ Testing 101. Ed. Springer Publishing, New York; 112,2009. Munke M, McDonald DM, Cronister A, Stewart JM, Gorlin RJ, Zackai EH. Oral-facial-digital syndrome type VI (Varadi syndrome): further clinical delineation. Am J Med Genet 1990, 35:360-369. Habre W, Sims C, D’Souza M. Anaesthetic management of children with Joubert syndrome.Paediatr Anaesth1997; 7:251–3.

Esquivils Like Water For Cholocate versus Mernissis Dreams of Trespass :: essays research papers

In both Fatima Mernissi’s novel, Dreams of Trespass, and Laura Esquivil’s Like Water for Chocolate, women are oppressed my invisible rules and boundries that are given to them by tradition and society. The female characters in both of these novels are given hardly any freedom and are expected to follow these unwritten laws or they will bring shame upon their families. However, in both of the novels we see that the lead female characters are able to gain power and break the frontiers that oppress them, by using the unwritten laws to their advantage. Ironically, they overcome their oppression by using that that oppresses them to their advantage. In Like Water for Chocolate, the protagonist, Tita, is oppressed by Mexican tradition. In Mexico, the youngest daughter of a family is not allowed to marry because her chief role in life should be to take care of her mother when she is too old to do so herself. Since Tita is the youngest daughter of her family, she is not allowed to marry the man she loves, Pedro, and is forced to spend her life cooking and caring for her mother while Pedro marries her sister. But as the novel goes on, cooking helps her break free from the restraint of her mother and tradition. Cooking is considered to be one for the things that she is oppressed by because she is forced to devote her life to it, but in actuality cooking helps her gain freedom and express emotion. She alters the traditional dinner recopies and is able to create food that is filled with so much passion that it allows her to communicate her love to Pedro. Every time Pedro tastes or smells one of her dishes he becomes overwhelmed with w armth and love. An example of this happening is when Tita prepares stuffed quail shortly after the death of Nacha, the family’s cook. â€Å"He (Pedro) couldn’t help closing his eyes in voluptuous delight and exclaiming ‘It is a dish for the gods’ (Like Water for Chocolate, page 51). Another time when Tita’s cooking strengthens her bond with Pedro is when she is cooking right after Pedro’s son is born. â€Å"Pedro, hearing her from the living room, experienced a sensation that was new to him. The sound of the pans bumping against each other, the smell of the almonds browning in the griddle, the sound of Tita’s melodious voice, singing as she cooked, had kindled his sexual feelings. Esquivil's Like Water For Cholocate versus Mernissi's Dreams of Trespass :: essays research papers In both Fatima Mernissi’s novel, Dreams of Trespass, and Laura Esquivil’s Like Water for Chocolate, women are oppressed my invisible rules and boundries that are given to them by tradition and society. The female characters in both of these novels are given hardly any freedom and are expected to follow these unwritten laws or they will bring shame upon their families. However, in both of the novels we see that the lead female characters are able to gain power and break the frontiers that oppress them, by using the unwritten laws to their advantage. Ironically, they overcome their oppression by using that that oppresses them to their advantage. In Like Water for Chocolate, the protagonist, Tita, is oppressed by Mexican tradition. In Mexico, the youngest daughter of a family is not allowed to marry because her chief role in life should be to take care of her mother when she is too old to do so herself. Since Tita is the youngest daughter of her family, she is not allowed to marry the man she loves, Pedro, and is forced to spend her life cooking and caring for her mother while Pedro marries her sister. But as the novel goes on, cooking helps her break free from the restraint of her mother and tradition. Cooking is considered to be one for the things that she is oppressed by because she is forced to devote her life to it, but in actuality cooking helps her gain freedom and express emotion. She alters the traditional dinner recopies and is able to create food that is filled with so much passion that it allows her to communicate her love to Pedro. Every time Pedro tastes or smells one of her dishes he becomes overwhelmed with w armth and love. An example of this happening is when Tita prepares stuffed quail shortly after the death of Nacha, the family’s cook. â€Å"He (Pedro) couldn’t help closing his eyes in voluptuous delight and exclaiming ‘It is a dish for the gods’ (Like Water for Chocolate, page 51). Another time when Tita’s cooking strengthens her bond with Pedro is when she is cooking right after Pedro’s son is born. â€Å"Pedro, hearing her from the living room, experienced a sensation that was new to him. The sound of the pans bumping against each other, the smell of the almonds browning in the griddle, the sound of Tita’s melodious voice, singing as she cooked, had kindled his sexual feelings.

A Campaign against KFC Corporation MGNT Essay

When contemplating critics of business and defenders of capitalism, the ongoing debate by The People for Ethical Treatment of Animals (PETA) against fast food restaurants should be mentioned. On January 6, 2003 a little girl named Payton Hull organized a PETA demonstration outside a KFC. The demands were for KFC to require the chicken’s suppliers to treat the chickens ethically in a humane way while processing them. In retrospect I agree with this request but in everyday life I just do not stop to think about how my food is processed. When I read and prepare to do paperwork on this subject it always tends to make my stomach a little uneasy. PETA organized and founded by Ingrid Newkirk has been very successful thus far in swaying many fast food restaurants to submit to request of transparency. KFC called the attacks â€Å"corporate terrorism†. Ingrid Newkirk even went as far as writing a nasty letter to the president of KFC stating that it was just an accident that the K FC president was born who she was instead of a chicken. Like me most consumers do not think where the chickens come from because we see the end final product. Which that being said it makes us realize that events held by PETA brings those images and staggering treatment procedures to the forefront. The organization has been successful with more than 1.2 million supporters. They create sit ins, use the internet and social media, and also go as far as using sexuality to get the point across. Former Playboy Playmates wearing bikinis pass out veggie hot dogs in Washington DC at the Annual Hot Dog Lunches. See more: Experiment on polytropic process Essay

Crime in Urban America Essay - 1051 Words

Crime in Urban America has been around for many years, it is atrocious and there are many reasons why people commit these crimes. Crime is a big issue all around the world and while there is more production of drugs and loss of jobs, the crime rate will continue to increase day by day. While there are many motives that contribute to crime the most obvious causes would be poverty which causes the poor to adapt into a violent and aggressive behavior to which later becomes ingrained into them. The environment where a person grows up in which could consist of gangs that participate in illegal activities. Abuse of drugs or alcohol attribute to crime because people commit abominable crimes while under the influence. The anger that an individual†¦show more content†¦The environment of where a person was raised is another leading cause of crime. When someone grows up in a place where they see all these bad things happening in their society it serves as a role model to them and they adapt other people’s actions. Growing up in a household where somebody does not have parents or a guardian telling them what is right from wrong leads you to do the unthinkable because they do not have any family direction showing you the right way to live life.† One of the most important environmental factors during childhood development is that of socialization or the way a child is ‘taught’ how to act†(Chemistry Web) Lack of faith causes a person to think of violence as their only way to get attention. When someone has no religious values, they think of all the bad things that are bothering them instead of the good that they can bring into their life. Gangs in an environment are a big cause of bringing crime to a society because they are the people who do the most outrageous crimes. 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