Palate Abnormalities Research Articles

Case Report of Lipoid Pneumonia: An Unusual Etiology of a Lung Cavity

Lipoid pneumonia is an uncommon non-infectious condition that results from the accumulation of lipids of animal, vegetable or mineral origin, in the lungs. Most often it is a result of aspiration from altered swallowing or cough mechanism. Children with palatal abnormalities debilitated older adults or adults with neurological or gastrointestinal disorders are commonly affected. Lipoid pneumonia should be considered as a differential for a lung cavity lesion, especially in patients at risk for aspiration. Such lesions can persist on long-term follow up. However, infection and malignancy should be ruled out.

Novel heterozygous mutation in TBX1 in an infant with hypocalcemic seizures.

.Patients with 22q11.2 deletion syndrome have characteristic facial appearance, palate abnormalities, hypoparathyroidism, thymic hypoplasia, and congenital heart disease. The 22q11.2 region includes TBX1 and 30 other genes. Analysis of Tbx1 transgenic mice showed that TBX1 was associated with the 22q11.2 deletion syndrome. In humans, TBX1 mutations have been reported in 22q11.2 deletion-negative patients with velocardiofacial syndrome or DiGeorge syndrome. Genotype-phenotype correlations are not fully understood in these patients. We report the case of an infant with a novel heterozygous TBX1 mutation who experienced hypocalcemic seizures. This patient had no palate abnormalities, cardiac anomalies, or the typical facial appearance observed in 22q11.2 deletion syndrome. The presence of thymic hypoplasia prompted us to perform G-banding, fluorescent in situ hybridization, and subsequent TBX1 analysis. We emphasize the importance of diagnosing thymic hypoplasia in hypocalcemic infants without 22q11.2 deletion for detecting TBX1 mutations.

The 22q11.2 deletion syndrome: Cancer predisposition, platelet abnormalities and cytopenias.

The 22q11.2 deletion syndrome (DS) is associated with variable phenotypic expression as findings range from severely affected individuals with the classical triad of DiGeorge and velocardiofacial syndromes, including congenital heart disease, immunodeficiency, hypocalcemia, and palatal abnormalities, to subtly affected adults who only come to attention following the diagnosis of a more severely affected child. The multiple manifestations can affect all organ systems, including the hematologic system resulting in baseline lower platelet counts for individuals with 22q11.2DS and increased platelet size. In addition, there may be an associated increased risk of bleeding. Individuals with 22q11.2DS are also at increased risk of autoimmune cytopenias that can complicate the evaluation or management of other manifestations. Finally, there may be an increased risk of malignancy, although the mechanism for this risk is not fully understood. This review summarizes the currently available data on hematologic/oncologic manifestations of 22q11.2DS and reports on our findings within a large cohort of individuals with the deletion.

Pediatric healthcare costs for patients with 22q11.2 deletion syndrome.

BackgroundThe 22q11.2 deletion syndrome is a variably expressed disorder that can include cardiac, palate, and other physical abnormalities, immunodeficiency, and hypocalcemia. Because of the extreme variability in phenotype, there has been no available estimate of the total medical expenditure associated with the average case.MethodsWe have developed a model to estimate the cost from the time of diagnosis to age 20. Costs were based on patients seen at a specialty center but also considered those components of care expected to have been provided by external healthcare facilities. Expense was based on billed medical charges extracted from the electronic medical billing system for all patients with a diagnosis of DiGeorge or velocardiofacial syndrome from 1993–2015. Expenditures included maternal prenatal care directly related to an affected pregnancy, molecular/cytogenetic diagnosis, consultations, surgery, and/or other treatment and management. Most mental health services (except inpatient), therapy related to cognitive, behavioral, speech, pharmacy, and nonmedical costs (special education, vocational, respite, lost earnings) were not included.ResultsData were available for 642 patients with 50.7% diagnosed prenatally or in the first year of life. The average cost for a patient was $727,178. Costs were highest for patients ascertained prenatally ($2,599,955) or in the first year of life ($1,043,096), those with cardiac abnormalities or referred for cardiac evaluation ($751,535), and patients with low T‐cell counts ($1,382,222).ConclusionThis study demonstrates that there are significant medical costs associated with 22q11.2 deletion syndrome.

Repair of Oropharyngeal Stenosis With Bilateral Buccal Myomucosal Flaps

Oropharyngeal stenosis (OPS) is a rare postoperative complication of adenotonsillectomy that can be a source of considerable patient distress and morbidity. Circumferential scarring of the soft palate and tonsillar pillars leads to narrowing of the oropharyngeal aperture. This case report describes the novel use of bilateral buccal myomucosal flaps for the repair of postoperative OPS in a 20-year-old woman presenting with dysphagia, odynophagia, dyspnea, and intermittent hypernasal speech. Postoperatively, the patient noted immediate improvement of her symptoms. At 1-month follow-up, she noted complete resolution of her symptoms with no dysphagia, nasal regurgitation, speaking difficulty, dyspnea, or gagging. The buccal flaps were well healed and completely intact, maintaining appropriate height of the tonsillar pillars. The buccal myomucosal flap is an effective tool for numerous palatal and oropharyngeal abnormalities and, as described in this case study, is a reliable, safe, and effective technique that can be considered for the reconstruction of postsurgical OPS.

Diagnosing subtle palatal anomalies: Validation of video-analysis and assessment protocol for diagnosing occult submucous cleft palate

IntroductionSubmucous cleft palate (SMCP) classically involves bifid uvula, zona pellucida, and notched hard palate. However, patients may present with more subtle anatomic abnormalities. The ability to detect these abnormalities is important for surgeons managing velopharyngeal dysfunction (VPD) or considering adenoidectomy. ObjectivesValidate an assessment protocol for diagnosis of occult submucous cleft palate (OSMCP) and identify physical examination features present in patients with OSMCP in the relaxed and activated palate positions. MethodsStudy participants included patients referred to a pediatric VPD clinic with concern for hypernasality or SMCP. Using an appropriately encrypted iPod touch, transoral video was obtained for each patient with the palate in the relaxed and activated positions. The videos were reviewed by two otolaryngologists in normal speed and slow-motion, as needed, and a questionnaire was completed by each reviewer pertaining to the anatomy and function of the palate. Results47 patients, with an average age of 4.6 years, were included in the study over a one-year period. Four videos were unusable due to incomplete view of the palate. The most common palatal abnormality noted was OSMCP, diagnosed by each reviewer in 26/43 and 30/43 patients respectively. Using the assessment protocol, agreement on palatal diagnosis was 83.7% (kappa = 0.68), indicating substantial agreement, with the most prevalent anatomic features being vaulted palate elevation (96%) and visible notching of hard palate (75%). ConclusionThe diagnosis of subtle palatal anomalies is difficult and can be subjective. Using the proposed video-analysis method and assessment protocol may improve reliability of diagnosis of OSMCP.

Clinical spectrum of DiGeorge syndrome – Experience of a single center

Objective: DiGeorge Syndrome (DGS), caused by a submicroscopic deletion in chromosome 22 (22q11.2), is the most common microdeletion syndrome in humans with an incidence of 1/400 live births. The condition is inherited in an autosomal dominant manner, though almost 90 % is due to a de novo mutation. Its phenotype ranges from mild to severe and it comprises congenital heart disease, palatal abnormalities, characteristic facial features, immune deficiency, developmental delay, parathyroid hypoplasia and renal, ocular, and skeletal malformations. Methods: We illustrate the presentation modalities of DGS in different ages through 4 clinical cases, patients that presented in the Pediatric Neurology Department in the last 10 years. Two patients had classical phenotypes and the others had global developmental delay and dysmorphic features; their diagnosis was confirmed after screening with arrayCGH. Results: Patient 1, a 4 year old boy with characteristic facial features, severe hipogammaglobulinemia and an interrupted Aortic arch. Patient 2, a 5 year old boy with characteristic DGS facial features, palatoschisis, hypotonia and global developmental delay. Both patients were diagnosed in the first month of life. Both phenotypes, highly suggestive since birth of classical DGS were confirmed through FISH (microdeletion of 22q11.2 and TBX1 gene). Patient 3, male, aged 14 has dysmorphic features, language and cognitive delay and anxiety disorder. Patient 4, female, aged 16, has pronounced facial dysmorphism both typical for DGS and unspecific features and severe developmental delay. They presented intellectual delay of unknown causes, both showing particular features, language delay and psychiatric disorders. An extended genetic screening with arrayCGH showed 22q11.21 deletions, demonstrating the broad phenotype of DGS. Conclusion: We emphasize the importance of genetic screening in cases of developmental delay which can lead to an early diagnosis and the formulation of an early intervention plan in order to prevent and limit the complications associated with DGS.

KBG syndrome: An Australian experience.

In 2011, heterozygous mutations in the ANKRD11 gene were identified in patients with KBG syndrome. Since then, 100 cases have been described with the expansion of the clinical phenotype. Here we present 18 KBG affected individuals from 13 unrelated families, 16 with pathogenic mutations in the ANKRD11 gene. Consistent features included intellectual disability, macrodontia, and the characteristic broad forehead with hypertelorism, and a prominent nasal bridge. Common features included hand anomalies, cryptorchidism, and a large number of palate abnormalities. Distinctive findings in this series included malrotation of the abdominal viscera, bilateral inguinal herniae in two patients, basal ganglia calcification and the finding of osteopenia in three patients. Nine novel heterozygous variants were found and the genotype-phenotype correlation was explored. This report highlights the need for thorough examination and investigation of the dental and skeletal systems. The results confirm the specificity of ANKRD11 mutations in KBG and further evidence for this transcription repressor in neural, cardiac, and skeletal development. The description of further cases of KBG syndrome is needed to further delineate this condition, in particular the specific neurological and behavioral phenotype.

SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations.

The SATB2‐associated syndrome is a recently described syndrome characterized by developmental delay/intellectual disability with absent or limited speech development, craniofacial abnormalities, behavioral problems, dysmorphic features, and palatal and dental abnormalities. Alterations of the SATB2 gene can result from a variety of different mechanisms that include contiguous deletions, intragenic deletions and duplications, translocations with secondary gene disruption, and point mutations. The multisystemic nature of this syndrome demands a multisystemic approach and we propose evaluation and management guidelines. The SATB2‐associated syndrome registry has now been started and that will allow gathering further clinical information and refining the provided surveillance recommendations. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Clinical and genetic aspects of KBG syndrome.

KBG syndrome is characterized by short stature, distinctive facial features, and developmental/cognitive delay and is caused by mutations in ANKRD11, one of the ankyrin repeat‐containing cofactors. We describe 32 KBG patients aged 2–47 years from 27 families ascertained via two pathways: targeted ANKRD11 sequencing (TS) in a group who had a clinical diagnosis of KBG and whole exome sequencing (ES) in a second group in whom the diagnosis was unknown. Speech delay and learning difficulties were almost universal and variable behavioral problems frequent. Macrodontia of permanent upper central incisors was seen in 85%. Other clinical features included short stature, conductive hearing loss, recurrent middle ear infection, palatal abnormalities, and feeding difficulties. We recognized a new feature of a wide anterior fontanelle with delayed closure in 22%. The subtle facial features of KBG syndrome were recognizable in half the patients. We identified 20 ANKRD11 mutations (18 novel: all truncating) confirmed by Sanger sequencing in 32 patients. Comparison of the two ascertainment groups demonstrated that facial/other typical features were more subtle in the ES group. There were no conclusive phenotype–genotype correlations. Our findings suggest that mutation of ANKRD11 is a common Mendelian cause of developmental delay. Affected patients may not show the characteristic KBG phenotype and the diagnosis is therefore easily missed. We propose updated diagnostic criteria/clinical recommendations for KBG syndrome and suggest that inclusion of ANKRD11 will increase the utility of gene panels designed to investigate developmental delay. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms

Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2β, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we report five individuals with de novo missense substitutions in CHD4 identified through whole-exome sequencing and web-based gene matching. These individuals have overlapping phenotypes including developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. The variants, c.3380G>A (p.Arg1127Gln), c.3443G>T (p.Trp1148Leu), c.3518G>T (p.Arg1173Leu), and c.3008G>A, (p.Gly1003Asp) (GenBank: NM_001273.3), affect evolutionarily highly conserved residues and are predicted to be deleterious. Previous studies in yeast showed the equivalent Arg1127 and Trp1148 residues to be crucial for SNF2 function. Furthermore, mutations in the same positions were reported in malignant tumors, and a de novo missense substitution in an equivalent arginine residue in the C-terminal helicase domain of SMARCA4 is associated with Coffin Siris syndrome. Cell-based studies of the p.Arg1127Gln and p.Arg1173Leu mutants demonstrate normal localization to the nucleus and HDAC1 interaction. Based on these findings, the mutations potentially alter the complex activity but not its formation. This report provides evidence for the roleof CHD4 in human development and expands an increasingly recognized group of Mendelian disorders involving chromatin remodeling and modification.

Associated factors and persistence of palatal groove in preterm infants: a cohort study.

BackgroundThere is a lack of evidence on the relationship between prematurity and palatal abnormalities. The aim of this study was to evaluate the incidence of palatal groove, the associated factors and the persistence time in preterm infants from birth to 24 months of age.MethodsThe children’s data, medical history and eating habits were collected using a questionnaire answered by the legal guardian and updated every dental visit. Natal and neonatal data were obtained from the medical records. During the orofacial examination, the presence or absence of a palatal groove was observed. In order to evaluate for associations between independent variables and the palatal groove, descriptive analyses and bivariate analyses were conducted using the Mann-Whitney, Pearson’s chi-squared and Fisher’s exact tests, when appropriate. The Poisson regression analysis was used to determine risk and protective factors for the occurrence of palatal groove. The significance level was 0.05. For the persistence of palatal groove, a survival analysis was used (Kaplan Meier method).ResultsSeventy-four preterm infants were monitored. Palatal groove occurred in n = 19 (25.7 %) and persisted for an average time of 12 months. Bivariate analysis showed a significantly higher occurrence of palatal groove in girls (68.4 % vs 40 % with non-occurrence of palatal groove) as well as in infants that stayed longer in the neonatal intensive care unit (NICU) (median 37 days vs 20 days), that did not have exclusive breastfeeding (94.7 % vs 69.1 %), were intubated (median five days vs one day) or used an orogastric tube (median 33 days vs 15 days). The quantitative data for ‘NICU’, ‘intubation’ and ‘orogastric tube’ were correlated and estimated as risk factors for palatal groove formation in the unadjusted Poisson regression analysis.ConclusionsPalatal groove occur transiently in approximately one quarter of preterm infants, especially in infants that stay longer in the NICU, are intubated or use an orogastric tube.

Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia

Chromosome 22q11.2 deletion syndrome is a clinically heterogeneous condition of intellectual disability, parathyroid and thyroid hypoplasia, palatal abnormalities, cardiac malformations and psychiatric symptoms. Hyperphagia and childhood obesity is widely reported in Prader-Willi Syndrome (PWS) but there is only one previous report of this presentation in chromosome 22q11.2 deletion syndrome. We describe two further cases of chromosome 22q11.2 deletion syndrome in which hyperphagia and childhood obesity were the presenting features. This may be a manifestation of obsessive behaviour secondary to some of the psychiatric features commonly seen in chromosome 22q11.2 deletion syndrome. Serious complications may result from hyperphagia and childhood obesity therefore early recognition and intervention is crucial. Due to the similar clinical presentation of these two patients to patients with PWS, it is suggested that the hyperphagia seen here should be managed in a similar way to how it is managed in PWS.

Prevalence of 22q11.2 microdeletion syndrome in Iranian patients with cleft palate.

Background:22q11.2 microdeletion syndrome is the most common multiple genetic disorder associated with learning disabilities, developmental delays, immune deficiency, hypocalcemia, and cleft palate. Finding some valid criteria for screening of 22q11.2 deletion syndromes in infants would be very helpful in early diagnosis and treatment.Materials and Methods:Since 69% of individuals with 22q11.2 deletion have a palatal abnormality, we studied the prevalence of 22q11.2 deletion syndrome in 378 Iranian patients during a 5-year period, including 291 patients affected with cleft palate only without cleft lip (CPO) and 87 patients affected with velopharyngeal incompetence (VPI) and/or submucous cleft palate (SMCP). DNA copy number was analyzed with multiplex ligation-dependent probe amplification (MLPA) technique.Results:In our study, 15/378 (3.97%) patients with palatal anomalies showed 22q11.2 deletion. Interestingly, this prevalence between syndromic patients was 15/104 (14.42%).Conclusion:It seems that SMCP or VPI, in addition to one or more another features of 22q11.2 deletions, especially developmental delay, may be good criteria for molecular investigation of 22q11.2 region.

Trans-oral endoscopic partial adenoidectomy does not worsen the speech after cleft palate repair

IntroductionAdenoid hypertrophy may play a role in velopharyngeal closure especially in patients with palatal abnormality; adenoidectomy may lead to velopharyngeal insufficiency and hyper nasal speech. Patients with cleft palate even after repair should not undergo adenoidectomy unless absolutely needed, and in such situations, conservative or partial adenoidectomy is performed to avoid the occurrence of velopharyngeal insufficiency. Trans-oral endoscopic adenoidectomy enables the surgeon to inspect the velopharyngeal valve during the procedure. ObjectiveThe aim of this study was to assess the effect of transoral endoscopic partial adenoidectomy on the speech of children with repaired cleft palate. MethodsTwenty children with repaired cleft palate underwent transoral endoscopic partial adenoidectomy to relieve their airway obstruction. The procedure was completely visualized with the use of a 70° 4mm nasal endoscope; the upper part of the adenoid was removed using adenoid curette and St. Claire Thompson forceps, while the lower part was retained to maintain the velopharyngeal competence. Preoperative and postoperative evaluation of speech was performed, subjectively by auditory perceptual assessment, and objectively by nasometric assessment. ResultsSpeech was not adversely affected after surgery. The difference between preoperative and postoperative auditory perceptual assessment and nasalance scores for nasal and oral sentences was insignificant (p=0.231, 0.442, 0.118 respectively). ConclusionsTransoral endoscopic partial adenoidectomy is a safe method; it does not worsen the speech of repaired cleft palate patients. It enables the surgeon to strictly inspect the velopharyngeal valve during the procedure with better determination of the adenoidal part that may contribute in velopharyngeal closure.

22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness - all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population.

Clinical Features in Patients With 22q11.2 Deletion Syndrome Ascertained by Palatal Abnormalities.

The aim of this study was to describe clinical features in subjects with palatal abnormalities and to assess the distribution of these features among those with and without 22q11.2 deletion. Descriptive cohort. One hundred patients with palatal abnormalities and suspicion of 22q11.2 DS were included. All patients were evaluated by a clinical geneticist, who completed a standardized clinical protocol. The 22q11.2 deletion screening was performed with fluorescence in situ hybridization using the TUPLE1 probe and multiplex ligation-dependent probe amplification using the P250-A1 kit. The 22q11.2 deletion was detected in 35 patients, in whom the most frequent clinical features were congenital heart disease (15/30 - 50%), developmental delay (19/35 - 54%), speech delay (20/35 - 57%), learning disabilities (27/35 - 77%), immunologic alterations (18/29 - 62%). In addition, the most common facial dysmorphisms in this group were long face (27/35 - 77%), typical nose (24/35 - 69%), and hooded eyelids (19/35 - 54%). Comparing features in patients with or without the deletion revealed significant differences (positively correlated with the deletion) for speech delay, learning disabilities, conductive hearing loss, number of dysmorphisms, long face, and hooded eyelids. Cleft lip and palate was negatively correlated with the deletion. The presence of speech delay, learning disabilities, conductive hearing loss, long face, and hooded eyelids should reinforce the suspicion of 22q11.2 DS in patients with palatal abnormalities and would help professionals direct clinical follow-up of these patients.

Developmental trajectories in 22q11.2 deletion.

Chromosome 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic condition, is the most common microdeletion syndrome affecting 1 in 2,000-4,000 live births and involving haploinsufficiency of ∼50 genes resulting in a multisystem disorder. Phenotypic expression is highly variable and ranges from severe life-threatening conditions to only a few associated features. Most common medical problems include: congenital heart disease, in particular conotruncal anomalies; palatal abnormalities, most frequently velopharyngeal incompetence (VPI); immunodeficiency; hypocalcemia due to hypoparathyroidism; genitourinary anomalies; severe feeding/gastrointestinal differences; and subtle dysmorphic facial features. The neurocognitive profile is also highly variable, both between individuals and during the course of development. From infancy onward, motor delays (often with hypotonia) and speech/language deficits are commonly observed. During the preschool and primary school ages, learning difficulties are very common. The majority of patients with 22q11.2DS have an intellectual level that falls in the borderline range (IQ 70-84), and about one-third have mild to moderate intellectual disability. More severe levels of intellectual disability are uncommon in children and adolescents but are more frequent in adults. Individuals with 22q11.2DS are at an increased risk for developing several psychiatric disorders including attention deficit with hyperactivity disorder (ADHD), autism spectrum disorder (ASD), anxiety and mood disorders, and psychotic disorders and schizophrenia. In this review, we will focus on the developmental phenotypic transitions regarding cognitive development in 22q11.2DS from early preschool to adulthood, and on the changing behavioral/psychiatric phenotype across age, on a background of frequently complex medical conditions.

Further supporting evidence for the SATB2-associated syndrome found through whole exome sequencing.

The SATB2-associated syndrome (SAS) was recently proposed as a clinically recognizable syndrome that results from deleterious alterations of the SATB2 gene in humans. Although interstitial deletions at 2q33 encompassing SATB2, either alone or contiguously with other genes, have been reported before, there is limited literature regarding intragenic mutations of this gene and the resulting phenotype. We describe five patients in whom whole exome sequencing identified five unique de novo mutations in the SATB2 gene (one splice site, one frameshift, and three nonsense mutations). The five patients had overlapping features that support the characteristic features of the SAS: intellectual disability with limited speech development and craniofacial abnormalities including cleft palate, dysmorphic features, and dental abnormalities. Furthermore, Patient 1 also had features not previously described that represent an expansion of the phenotype. Osteopenia was seen in two of the patients, suggesting that this finding could be added to the list of distinctive findings. We provide supporting evidence that analysis for deletions or point mutations in SATB2 should be considered in children with intellectual disability and severely impaired speech, cleft or high palate, teeth abnormalities, and osteopenia.

Zespół mikrodelecji 22q11.2 (zespół DiGeorge’a) bez współistniejącej wady serca – analiza fenotypu pacjentów i problemy diagnostyczne

IntroductionDeletion of chromosome 22q11.2, which causes DiGeorge syndrome, is one of the most frequently diagnosed microdeletion syndromes in the human. It is characterised by a wide variety of symptoms. The main symptoms consist of congenital heart diseases, particularly conotruncal malformations, characteristic facial dysmorphism, palatal abnormalities, an immune deficiency and hypocalcemia.We present phenotypical analysis of 15 patients with DiGeorge syndrome without structural heart disease. A diagnosis of DiGeorge syndrome was confirmed by Multiplex Ligation-dependent Probe Amplification (MLPA) and Fluorescent in situ Hybridization (FISH) with a specific probe. ResultsFISH method was used in 10 patients in genetic diagnosis of microdeletion 22q11.2 syndrome, and MLPA method confirmed that FISH analysis was used in 5 patients. None of the patient exhibited heart disease in an ultrasound examination. Developmental delay (13/15), delay in emergence of language (8/15), palatal abnormalities (10/15) and frequent infections (11/15) were observed. All the patients presented characteristic facial features. ConclusionsIt is difficult to diagnose DiGeorge syndrome in patients who do not present heart disease. In such cases careful phenotypical analysis and microdeletions screening with MLPA method may be helpful to make a diagnosis.To establish appropriate therapy and further clinical evaluation exact and early diagnosis is crucial. There lacks diagnostic guidelines for patients with unexplained developmental delay and/or developmental malformations.