Palate Abnormalities Research Articles

Otitis media in five cats associated with soft palate abnormalities

The medical records of five cats that were diagnosed with otitis media and soft palate abnormalities, three of which had concurrent otitis interna, were reviewed retrospectively. The animals presented with...

Hypoglossia with Mandibular and Palatal Abnormalities

ABSTRACT Tongue is the most mobile organ of the body with multiple functions, such as speech, mastication, taste and swallowing. Numerous congenital and developmental disorders of the tongue have been reported in literature. Hypoglossia, also known as microglossia, is one of the rare anomalies. Usually hypoglossia is associated with many other systemic abnormalities but rarely found as an isolated entity. Lack of tongue development leads to decreased mandibular growth. The aim of this article is to report a rare case of isolated hypoglossia and resultant micrognathia. Presence of palatal and faucial pillar abnormalities with hypoglossia which is extremely rare is also highlighted in our report. How to cite this article Shetty S, Anusha RL, Thomas PS, Babu SG. Hypoglossia with Mandibular and Palatal Abnormalities. Int J Phonosurg and Laryngol 2012;2(2):85-87.

Chromosome 22q11.2 deletion syndrome in African‐American patients: A diagnostic challenge

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with numerous and variable clinical manifestations including conotruncal heart abnormalities, palatal anomalies, hypoparathyroidism, immune deficiency, and cognitive deficits. The clinical suspicion of this syndrome is often heightened by the presence of characteristic facial features. A previous report highlighted the under-diagnosis of this condition in African Americans, thought to be related to a paucity of typical facial features. We ascertained the largest cohort (n = 50) of African-American individuals with 22q11DS reported thus far, across five genetics centers in the United States and report on their facial and other phenotypic features. About 3/4 of our cohort has at least one dysmorphic facial feature. Auricular abnormalities, especially small ears, are the most common dysmorphic facial feature followed by nasal and ocular abnormalities. Skeletal findings are seen in about 2/3 of our cohort, higher than the typical frequency reported in 22q11DS. Cardiac anomalies, developmental delay, and palatal abnormalities are seen at a lower frequency in our cohort. Thus, it is evident that the features traditionally associated with 22q11DS are difficult to recognize in African-American individuals with this syndrome, due to both altered frequencies of major anomalies and a non-classic facial appearance. Therefore, a high index of suspicion is needed to recognize 22q11DS in African-American individuals.

Minor physical anomalies and neurological soft signs in patients with schizophrenia and their siblings

Neurological soft signs (NSSs) and minor physical anomalies (MPAs) are consistently found at higher rates in individuals with schizophrenia compared to healthy controls. However, limited research has been conducted on these traits among the biological relatives of these patients. We aimed to identify the possible origins of these traits in schizophrenia by exploring them in patients with schizophrenia, their healthy siblings and normal controls. Ninety-six patients with schizophrenia, their 66 non-psychotic siblings and 52 healthy subjects were studied. Measures included the Neurological Evaluation Scale, a structured examination for detection of minor physical anomalies, stroop and verbal fluency tests for cognitive assessment, and scales for assessment of disease severity in patients; the Scale for the Assesment of Negative Symptoms and the Scale for the Assesment of Positive Symptoms. Increased rates of NSSs and high MPA scores were found in both the patients and their siblings as compared to normal controls. MPAs in several body regions were similar (eyes, ears, hands and feet) or correlated (innercanthal width and head circumference) between patients and their respective siblings. However, there was little similarity in palate and tongue anomalies between these subjects. These results suggest that NSSs and MPAs might represent two distinct markers of risk for schizophrenia. MPAs at different locations may also represent distinct pathological processes, such that palate and tongue abnormalities are more likely to represent non-familial rather than familial factors compared to other abnormalities.

The role of cephalometry in assessing velopharyngeal dysfunction in velocardiofacial syndrome

To report our experience with cephalometry in evaluating velopharyngeal dysfunction (VPD) in velocardiofacial syndrome (VCFS) and its utility in assessing the role of cervical spine abnormalities in VPD, prior to surgical correction of VPD. Clinical charts and cephalometric radiographs done prior to surgery for VPD were retrospectively analyzed to ascertain velopharyngeal measurements and cervical spine abnormalities. Twenty-six patients (age: 6-23 years) with molecularly confirmed VCFS. Wake Forest University Health Sciences (1997-2005). Cranial base angle, nasopharyngeal depth, velum length, and Need ratio at rest, velar dimple location, and velopharyngeal length during phonation; information on presence/absence of submucous cleft palate and cervical spine abnormalities were also obtained. The relationship between C1 anterior arch abnormalities and Need ratio was examined. Seventy-three percent of the VCFS patients had excessive nasopharyngeal depth, 80% had an abnormal Need ratio, 50% had a short velum, 81% had a submucous or occult submucous cleft palate, 90.5% had a cervical spine abnormality (C1 anterior arch abnormalities in 38%) and 11.5% had platybasia. There was a significant difference in the Need ratio between patients with and without C1 anterior arch abnormalities. Cephalometry can be used to delineate factors such as C1 vertebral abnormalities, excessive pharyngeal depth, and short velum that contribute to VPD in VCFS. This would help otolaryngologists better understand the anatomy prior to surgical treatment of VPD. This is the first study to highlight the frequent occurrence of C1 anterior arch abnormalities in VCFS.

Correlation of resting and exercising endoscopic findings for horses with dynamic laryngeal collapse and palatal dysfunction

To correlate resting and exercising endoscopic grades of laryngeal function in horses undergoing high-speed treadmill endoscopy (HSTE) using the Havemeyer grading system. To correlate dorsal displacement of the soft palate (DDSP) seen at rest with palatal function during exercise. Records of horses that underwent HSTE examination (1999-2009) were reviewed. Resting laryngeal function score and other abnormalities noted on resting endoscopy were recorded as were results of HSTE. Results of resting and exercising endoscopic findings were correlated. 281 horses underwent HSTE. There was significant correlation between grade of laryngeal function at rest (grades 1-4) and exercise (ρ=0.53, P<0.001) and between resting subgrades 3.1, 3.2 and 3.3 and exercising grades of laryngeal function (ρ=0.43, P=0.0017). DDSP was observed at rest significantly more often in horses that developed DDSP during HSTE than those without DDSP during HSTE (RR=4.1, P<0.001). The sensitivity and specificity of DDSP seen during resting endoscopy as a test for DDSP occurring during exercise were 25.5 and 95.1% respectively (positive predictive value 0.57, negative predictive value 0.83). The results of the current study support the use of the Havemeyer system for grading laryngeal function in the resting horse, and corroborate findings of previous studies correlating resting and exercising palatal abnormalities. Studies that use the presence of spontaneous DDSP during resting endoscopic examination as an inclusion criterion for investigating efficacy of treatments for DDSP are likely to have a low proportion of horses with false positive diagnoses.

Detection of lip, alveolar ridge and hard palate abnormalities using two‐dimensional ultrasound enhanced with the three‐dimensional reverse‐face view

The aim of this study was to assess conventional two-dimensional (2D) ultrasound enhanced with a three-dimensional (3D) ultrasound technique, the 'reverse-face' view (3D-RF) in prenatal evaluation of the involvement of the lips, alveolar ridge and secondary palate in suspected isolated orofacial clefting. One hundred and twenty-four cases of suspected orofacial clefting diagnosed by a routine 2D ultrasound scan were referred for specialist ultrasound at 20-34 weeks' gestation for a detailed assessment of the lips and palate using both 2D and 3D ultrasound. For the 3D examination the lips and alveolar ridges were examined both in profile and in the frontal plane. The palate was then assessed in the reverse coronal view by rotating the face through 180° on the vertical axis to produce the 3D-RF view. Antenatal diagnoses were compared with postnatal findings. Left and right lip and alveolar ridge defects were counted separately according to the Kernohan 'striped Y' classification. Of 124 patients, 110 had isolated facial clefts and were available for follow-up; in 10, 3D-RF views were not successfully obtained, leaving 100 cases for assessment. The sensitivity of the 2D enhanced with 3D-RF technique for the diagnosis of cleft of the lip was 116/122 (95%), false-positive rate (FPR) 7.7%; for alveolar ridge was 87/103 (84.5%), FPR 7.2%; and for hard palate was 61/68 (89.7%), FPR 15.6%. The data reported represent the largest series of orofacial abnormalities diagnosed by 2D ultrasound and enhanced with 3D imaging to refine the detection of clefts of the hard palate. The technique is feasible in 90% of patients in whom almost 90% have a correct classification of clefts of the lip, alveolar ridge and palate.

The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field

We described the morphology of the sella turcica in individuals with velocardiofacial syndrome (VCFS), also known as chromosome 22q11.2 deletion syndrome, and compared the morphology with that of a control group of individuals from the Oslo University Craniofacial Growth Archive. The aim was to measure the cranial base angles in individuals with VCFS and, if possible, to discover the developmental field that may be involved in the condition. The study included 33 patients with VCFS from the Copenhagen Cleft Palate Center, Denmark. The genotype was confirmed by fluorescence in situ hybridization. The morphology of the sella turcica was described and measurements of the cranial base angles were performed on lateral cephalometric radiographs. The VCFS individuals had larger deviations in the morphology of the sella turcica compared to individuals from the Oslo University Craniofacial Growth archive. The deviations were mostly in the posterior part of the dorsum sellae. Individuals with VCFS had increased cranial base angles. The results of this study combined with the information in the literature on the main defects in VCFS (palatal abnormalities, cardiac anomalies, thymic hypoplasia or aplasia, hypothyroidism, and posterior brain abnormality), suggest involvement of a specific developmental field.

Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.

Mesomelic dysplasia with acral synostoses Verloes–David–Pfeiffer type: Follow‐up study documents progressive clinical course

Verloes-David-Pfeiffer mesomelia-synostoses syndrome is an autosomal-dominant form of mesomelic dysplasia comprising typical acral synostoses combined with ptosis, hypertelorism, palatal abnormality, CHD, and ureteral anomalies. Since the original reports in 1995, two other patients have been described with this syndrome, one of them the patient reported in 1998 by Day-Salvatore. In this article, we report on the follow-up of some of the original cases and review the literature. We confirm that the Verloes-David-Pfeiffer syndrome (VDPS) is a progressive skeletal disorder that despite repeated corrective surgical intervention leads to severe limb deformities. No mutations were detected in the FLNB gene. To date, the cause and the pathogenesis of VDPS remain unknown. The latter is characterized in this study as a syndromic type of skeletal dysplasia because besides congenital malformations and multiple acromelic synostoses arising prenatally, VDPS manifests in postnatal life as a severe osteochondrodysplasia.

FISH spots microdeletion in heart defects

AbstractThe 22q11.2 microdeletion is found in most of DiGeorge and velocardiofacial syndromes. These individuals have a wide range of anomalies including congenital heart disease, palatal abnormalities, characteristic facial features, hypocalcaemia, immune deficiency, and learning difficulties. Congenital heart disease, particularly conotruncal malformations are associated with 29% of deletions. This syndrome may be inherited as an autosomal dominant trait, but the majority of patients (93%) have a de novo deletion. To access the presence of the microdeletion in those individuals whose phenotipic changes suggested abnormalities in chromosome 22, a study has been made in several children with congenital heart defects.

Differential developmental toxicities of di‐n‐hexyl phthalate and dicyclohexyl phthalate administered orally to rats

The objective of this study was to evaluate the developmental toxic potential of di-n-hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague-Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg(-1) per day, by gavage, on gestational days (GD) 6-20. Maternal food consumption and body weight gain were significantly reduced at 750 mg kg(-1) per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused dose-related developmental toxic effects, including marked embryo mortality at 750 mg kg(-1) per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and significant decreases in fetal weight at 500 and 750 mg kg(-1) per day. Significant delay of ossification and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg(-1) per day. DCHP produced fetal growth retardation at 750 mg kg(-1) per day, as evidenced by significant reduction of fetal weight. DnHP and DCHP induced a significant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a significant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg(-1) per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP.

Physical Manifestations of Neurodevelopmental Disruption: Are Minor Physical Anomalies Part of the Syndrome of Schizophrenia?

The well-documented excess of minor physical anomalies (MPAs) among individuals with schizophrenia generally supports the neurodevelopmental model, which posits that both genetic and environmental factors contribute to structural and functional brain changes in the intrauterine and perinatal periods that predispose one to developing schizophrenia. This review synthesizes select areas of research findings on MPAs to address the question, Are MPAs part of the syndrome of schizophrenia? Although MPAs are not specific to schizophrenia, their presence in some patients indicates that aberrations in the development of the nervous system contribute to risk for the disorder. The broadly defined, heterogeneous MPA construct may be of limited value in further elucidating the specific pathophysiology of schizophrenia, though particular anomalies, such as those pertaining to nasal volumes, palatal abnormalities, or craniofacial morphology, may be informative. Given the availability of more sophisticated microarray technologies, and in light of recent findings on spontaneous mutations in patients with schizophrenia, it is possible that MPAs will prove to be useful in identifying etiologic subtypes and/or the loci of genetic risk factors. It remains to be determined whether MPAs-which, of course, are fixed markers present throughout childhood and adolescence well before the onset of the prodrome and psychosis-may have utility in terms of risk stratification for future preventive efforts. Taken together, research findings on MPAs indicate that these minor anomalies are indeed part of some schizophrenia syndromes, representing a stable systemic or physical set of manifestations of the underlying neurodevelopmental processes that lead to the illness.

Successful Isotretinoin Treatment of Acne in a Patient with Apert Syndrome

Sir, Apert syndrome (acrocephalosyndactyly type I), first described in 1906 by the French physician Eugene Apert, is a rare autosomal dominant congenital disorder characterized by the premature obliteration of the craniofacial sutures and syndactyly of the hands and feet (1). In most patients it is caused by a localized mutation in the gene encoding for the fibroblast growth factor receptor (FGFR2), which is responsible for the development of embryonic skeleton, epithelial structures and connective tissue (2). An incidence of 1:160,000 live births was found in a British study (1), but a higher birth prevalence (1:65,000 or 15.5 per million) was estimated several decades later (3). More than 98% of cases are caused by a new mutation, which is of paternal origin, and association with older paternal age has been implicated. The irregular obliteration of the cranial sutures results in different craniofacial deformities, hypertelorism, dental and palatal abnormalities and a tendency towards proptosis of the eyes (1, 4). Several other skeletal deformities as well as cardiovascular, urogenital, gastrointestinal, respiratory and skin abnormalities have been described. Increased intracranial pressure may lead to hydrocephalus, abnormal brain development, and different levels of mental retardation, blindness and death. Early neurosurgical intervention is therefore essential for a good prognosis in these patients (4). Since 1970 Apert syndrome has been discussed also in dermatological literature; Solomon et al. (5) were the first to describe pilosebaceous abnormalities in these patients. Early appearance of widespread and severe acne, resistant to conventional therapies, is a common feature in these patients. We describe here a patient with Apert syndrome and severe acne who had a good response to treatment with isotretinoin, and discuss previous reports of the use of oral isotretinoin in this syndrome.

22q11.2 Distal Deletion: A Recurrent Genomic Disorder Distinct from DiGeorge Syndrome and Velocardiofacial Syndrome

Microdeletions within chromosome 22q11.2 cause a variable phenotype, including DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). About 97% of patients with DGS/VCFS have either a common recurrent approximately 3 Mb deletion or a smaller, less common, approximately 1.5 Mb nested deletion. Both deletions apparently occur as a result of homologous recombination between nonallelic flanking low-copy repeat (LCR) sequences located in 22q11.2. Interestingly, although eight different LCRs are located in proximal 22q, only a few cases of atypical deletions utilizing alternative LCRs have been described. Using array-based comparative genomic hybridization (CGH) analysis, we have detected six unrelated cases of deletions that are within 22q11.2 and are located distal to the approximately 3 Mb common deletion region. Further analyses revealed that the rearrangements had clustered breakpoints and either a approximately 1.4 Mb or approximately 2.1 Mb recurrent deletion flanked proximally by LCR22-4 and distally by either LCR22-5 or LCR22-6, respectively. Parental fluorescence in situ hybridization (FISH) analyses revealed that none of the available parents (11 out of 12 were available) had the deletion, indicating de novo events. All patients presented with characteristic facial dysmorphic features. A history of prematurity, prenatal and postnatal growth delay, developmental delay, and mild skeletal abnormalities was prevalent among the patients. Two patients were found to have a cardiovascular malformation, one had truncus arteriosus, and another had a bicuspid aortic valve. A single patient had a cleft palate. We conclude that distal deletions of chromosome 22q11.2 between LCR22-4 and LCR22-6, although they share some characteristic features with DGS/VCFS, represent a novel genomic disorder distinct genomically and clinically from the well-known DGS/VCF deletion syndromes.

Effect of Maternal Restraint Stress on Fetal Development of ICR Mice

The present study was conducted to elucidate the susceptibility of embryos and fetuses at different gestational stages to the maternal stress in mice. Groups of pregnant ICR mice were subjected to daily 12-h restraint stress, taped in the supine position on a plastic board, on gestational days (GD) 1-4, 5-8, 9-12 and 13-16, respectively. Caesarean sections were performed on gestational day 18, and the fetuses were weighed and examined for morphological defects. During the daily restraint for 4 days, the maternal body weights markedly decreased. Although the body weights recovered gradually after termination of the stress, the recovery was not full until the final stage of pregnancy. Interestingly, restraint stress caused growth retardation of the fetuses, leading to a significant decrease in their body weights, and increased early and late resorptions of embryos and fetuses according to the stress periods. Although the preceding (GD1-4) and concurrent (GD5-8) stresses did not affect embryonic implantation, restraint stress on GD9-12 caused cleft palate. Whereas vertebral abnormalities, mainly bipartite ossification, were observed only in animals stressed on GD5-8, abnormalities of sternebrae, exhibiting asymmetric or bipartite ossification, were enhanced by the stress at all of the gestational stages. On the other hand, the incidence of other malformations including renal malposition and costal abnormalities was not increased by stress at any of the 4 stages. Taken together, the results suggest that intensive restraint stress influences the maternal body weight resulting in growth retardation and increased mortality of embryos and fetuses, in addition to gestational stage-specific ventricular dilatation, cleft palate and sternal abnormalities.

Videomanometric Evaluation of Pharyngo‐oesophageal Dysmotility in Children With Velocardiofacial Syndrome

Videomanometric Evaluation of Pharyngo‐oesophageal Dysmotility in Children With Velocardiofacial Syndrome

Van den Ende–Gupta syndrome: Laryngeal abnormalities in two siblings

In 1992, van den Ende et al. first reported an autosomal recessive multiple congenital anomaly syndrome characterized by blepharophimosis, arachnodactyly, and congenital contractures in a Brazilian girl born to consanguineous parents. Since then, nine total patients have been reported with van den Ende-Gupta syndrome (VDEGS), and the syndrome's phenotype has been found to also include additional dysmorphic facial features, palatal abnormalities, and slender skeletal features. We present two African-American sisters born to nonconsanguineous parents who have been diagnosed with VDEGS. Both sisters developed stridor and were found to have an unusual malformation characterized by large, globular cuneiform cartilages, shortened aryepiglottic folds, a tightly coiled epiglottis, and laryngomalacia. Both patients underwent supraglottoplasty with a successful outcome. A review of the literature reveals that airway problems have been reported in a previous patient. However, no specific airway anomaly has been reported. We suggest that all patients with VDEGS and stridor undergo direct laryngoscopy with consideration for surgical correction.

Unilateral multicystic dysplastic kidney in infants exposed to antiepileptic drugs during pregnancy

Prenatal exposure to antiepileptic drugs (AEDs) increases the risk of major congenital malformations (MCM) in the fetus. AED-related abnormalities include heart and neural tube defects, cleft palate, and urogenital abnormalities. Among the various congenital anomalies of the kidney and urinary tract (CAKUT), multicystic dysplastic kidney (MCDK) disease is one of the most severe expressions. Although prenatal ultrasound (US) examination has increased the prenatal diagnosis of MCDK, the pathogenesis is still unclear. We report on four cases of MCDK in infants of epileptic women treated with AEDs during pregnancy. From October 2003 to June 2006, we observed four infants with unilateral MCDK born to epileptic women. Three patients were considered to have typical features of multicystic dysplastic kidney, and one infant was operated because of a cystic pelvic mass in the absence of a kidney in the left flank. The macroscopic appearance of this mass showed an ectopic multicystic kidney confirmed by histological findings. All patients have been studied by US scans, voiding cystourethrogram (VCUG), and radionuclide screening isotope imaging. The prenatal exposure to AEDs increases the risk of major congenital malformations from the background risk of 1-2% to 4-9%. AEDs may determine a defect in apoptosis regulation that could lead to abnormal nephrogenesis, causing MCDK. Carbamazepine (CBZ) and phenobarbital (PHB) during pregnancy should be used at the lowest dosage compatible with maternal disease. The reduction, or even suspension, of drug dosage should be achieved from the periconceptional period to the first 8 weeks of gestation to avoid any interference with organogenesis.

Behavioral problems in relation to intelligence in children with 22q11.2 deletion syndrome: A matched control study

The 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with palatal abnormalities, cardiac defects, a characteristic facial appearance, learning difficulties, and delays in speech and language development. Various behavioral disorders and psychiatric illnesses have also been reported. There is much debate as to whether the behavioral problems are caused by factors such as medical discomfort, facial abnormalities or a lower intelligence, or whether they are independently related to the genetic abnormality ("behavioral phenotype"). We examined the relationship between intelligence level and behavioral problems. A group of 69 children with 22q11DS was compared with 69 children with craniofacial anomalies (CFA) using the child behavior checklist (CBCL). The matches between individual children were based on their total IQ scores. Use of the CBCL norm scores covered the corrections for age and sex. The group of 22q11DS children showed significantly more behavioral problems than the CFA group: this was especially apparent on the CBCL subscales "withdrawn," "anxious/depressed," "delinquent behavior," "aggressive behavior," "somatic complaints," and "social problems." We found no correlation between IQ score and behavioral problems in the 22q11DS group, which was remarkable because, comparable with the general population, intellectual disabilities were a predictor of behavioral problems in the CFA group. 22q11DS children with relatively higher IQs showed more problems of an internalizing than an externalizing nature, whereas the 22q11DS children with lower IQs showed various behavioral problems. The absence of a statistically significant correlation between intelligence and behavior problems in the group of 22q11DS children is tentative evidence for a 22q11DS behavioral phenotype.