Parental factors in prenatal decision making and the impact of prenatal genetic counseling: a study on Turkish families.

OBJECTIVE: This study explored the social factors affecting prenatal decision making, the impact of genetic counseling on prenatal decision making, and how genetic counseling is perceived by Turkish women. METHOD: A standardized questionnaire was given to 231 patients, before and after genetic counseling, at Hacettepe University Ihsan Dogramaci Children's Hospital in 2007-2008. RESULTS: The level of education was an important factor both in prenatal decision making and in the patients' perception of genetic counseling. Decisions of pregnancy termination differed by geographic region of referral and history of healthy children but the differences were not statistically significant. The decisions were not influenced by poor obstetric history, number and sex of previous children, and disability of previous children. CONCLUSION: The level of education and the geographic region of referral in Turkey had an effect on the prenatal decisions and on the amount of prenatal genetic counseling received by the individuals.

Searching for Copy Number Changes in Nonsyndromic X-Linked Intellectual Disability.

Intellectual disability (ID) has a prevalence of 2-3% with 0.3% of the population being severely retarded. Etiology is heterogeneous, owing to numerous genetic and environmental factors. Underlying etiology remains undetermined in 75-80% of mildly disabled patients and 20-50% of those severely disabled. Twelve percent of all ID is thought to be X-linked (XLID). This study covers copy number analysis of some of the known XLID genes, using multiplex ligation-dependent probe amplification (MLPA) in 100 nonsyndromic patients. One of the patients was found to have duplication in all exons of MECP2 gene, and another had duplication in the fifth exon of TM4SF2/TSPAN7 gene. Affymetrix® 6.0 whole-genome SNP microarray confirmed the duplication in MECP2 and showed duplication of exons 2-7 in TM4SF2/TSPAN7, respectively. MECP2 duplication has recently been recognized as a syndromic cause of XLID in males, whereas duplications in TM4SF2/TSPAN7 are yet to be determined as a cause of XLID. Being an efficient, rapid, easy-to-perform, easy-to-interpret, and cost-effective method of copy number analysis of specific DNA sequences, MLPA presents wide clinical utility and may be included in diagnostic workup of ID, particularly when microarrays are unavailable as a first-line approach.

Opinions of Turkish physicians towards termination of pregnancy for fetal disorders.

Termination of pregnancy (ToP) raises ethical dilemmas. Although ToP for fetal disorders is commonly approved by health professionals, their opinions and attitudes are influenced by a diversity of cultural contexts. The aim of the study is to investigate Turkish physicians' opinions on ToP for fetal disease and the hypothesis is that their opinions are influenced by whether they face any disabilities of affected children or not. We aimed to survey by a questionnaire the opinions of Turkish physicians towards ToP for untreatable fetal disorders. A group of 250 subjects was included in the study. Physicians' approval of parents' decision for ToP was higher for disorders that they encounter more frequently during their daily work. Their opinions were not statistically different when compared for gender and marital status, however, having children of their own caused significant differences for some of the disorders. Approximately 65% of the participants responded that families alone should have the right to decide on ToP. The results confirm that health professionals may have differences in perception of severity of diseases, based on their clinical experience. Physicians encountering affected children more likely approve ToP for that particular disease.

Identification of point mutations and large rearrangements in the BRCA1 gene in 667 Turkish unselected ovarian cancer patients.

OBJECTIVE: The aim of this study was to evaluate the prevalence and spectrum of a known founder mutation, 5382insC and large genomic rearrangements (LGRs) in BRCA1 in ovarian cancer patients in Turkey. The additional aim was to determine the genetic testing strategy in Turkish breast/ovarian cancer family. METHODS: Six hundred and sixty-seven ovarian cancer patients from five large geographical regions in Turkey, 61 of which had family history of breast/ovarian cancer, were tested for the mutation 5382insC by mutagenically separated polymerase chain reaction and direct sequencing of the entire coding sequence and the splicing sites. Additionally, multiplex ligation-dependent probe amplification (MLPA) was performed for large mutational scanning of BRCA1 gene in unselected ovarian cancer. RESULTS: In this study, BRCA1 point mutations were observed in 1% of all patients and 9.8% of familial cases: 5382insC, unique novel missense variant-G1748S and unclassified splice site variant IVS20+5A>T. 5382insC was observed in two patients. However, G1748S, previously unreported, was found in four patients and thus led to the conclusion that this mutation may be unique to Turkey. A splice site variant, IVS20+5A>T, was detected in three patients, with two of them including G1748S and IVS20+5A>T, together. Using MLPA, six different distinct LGRs in BRCA1 were observed: the deletion of E1A-1B-2, E11, E17-19, E18 and E18-19 and duplication of E5-9. The prevalence of LGRs in this study was 40.9% among patients with family history. The deletion of E1A-1B-2 was the common mutation, and patients with this deletion were referred to us from four different geographical regions in Turkey. Therefore, it was hypothesized that this deletion covering E1-2 is common in Turkey. CONCLUSION: LGRs in BRCA1 were strongly associated with positive family history among the Turkish population. On the basis of these findings, it can be recommended that a low-cost screening for LGRs in BRCA1 may be the first-line mutation detection method in families with strong breast/ovarian cancer history in Turkey.

Kabuki syndrome and trisomy 10p.

Kabuki syndrome (KS) (MIM 147920) is a multiple congenital anomalies/mental retardation syndrome of unknown cause. There is multisystem involvement of anomalies, including 1) unique facial features, 2) postnatal growth retardation, 3) mild-to-moderate mental retardation, 4) skeletal anomalies and 5) dermatoglyphic abnormalities. Kabuki syndrome remains a clinical diagnosis despite significant research on detection of the genetic cause. We present 10 patients with Kabuki syndrome with a brief overview of the syndrome. An additional male patient and his affected aunt, both with trisomy 10p due to unbalanced segregation of a familial translocation, are also discussed for overlapping features and differential clinical diagnosis of the two conditions. Considering a significant overlap in clinical pictures of Kabuki syndrome and trisomy 10p in these two patients, as well as the previous patients with chromosomal abnormalities, we conclude that chromosome analysis is an important step in clinical work-up of patients with Kabuki syndrome.

Homozygous FGF3 mutations result in congenital deafness with inner ear agenesis, microtia, and microdontia.

Homozygous mutations in the fibroblast growth factor 3 (FGF3) gene have recently been discovered in an autosomal recessive form of syndromic deafness characterized by complete labyrinthine aplasia (Michel aplasia), microtia, and microdontia (OMIM 610706 - LAMM). In order to better characterize the phenotypic spectrum associated with FGF3 mutations, we sequenced the FGF3 gene in 10 unrelated families in which probands had congenital deafness associated with various inner ear anomalies, including Michel aplasia, with or without tooth or external ear anomalies. FGF3 sequence changes were not found in eight unrelated probands with isolated inner ear anomalies or with a cochlear malformation along with auricle and tooth anomalies. We identified two new homozygous FGF3 mutations, p.Leu6Pro (c.17T>C) and p. Ile85MetfsX15 (c.254delT), in four subjects from two unrelated families with LAMM. The p.Leu6Pro mutation occurred within the signal site of FGF3 and is predicted to impair its secretion. The c.254delT mutation results in truncation of FGF3. Both mutations completely co-segregated with the phenotype, and heterozygotes did not have any of the phenotypic findings of LAMM. Some affected children had large skin tags on the upper side of the auricles, which is a distinctive clinical component of the syndrome. Enlarged collateral emissary veins associated with stenosis of the jugular foramen were noted on computerized tomographies of most affected subjects with FGF3 mutations. However, similar venous anomalies were also detected in persons with non-syndromic Michel aplasia, suggesting that a direct causative role of impaired FGF3 signaling is unlikely.

Coexistent mosaic monosomy 21 and fragile X syndrome in a mentally retarded male patient.

Fragile X syndrome (FXS) is a well-recognized mental retardation syndrome with characteristic facial features and behavioural phenotype. Monosomy 21 is a rare cytogenetic aberration for which clinical features were incompletely defined since full monosomy 21 is incompatible with life. A 5-year-old male patient with FXS and low-grade mosaicism for full monosomy 21 (46,XY[96%]/45,XY,-21[4%]) is presented. He had lack of speech and severely impaired social skills, hyperactivity, stereotypical hand movements, a special interest towards moving colourful items and a short attention span for other objects around. He had macrocephaly, a rather long face, prominent occiput and prominent midface, retrognathia, down-slanting palpebral fissures, hypertelorism and cup-shaped, posteriorly rotated and low-set ears. Full monosomy in the aberrant cell line was proven by whole chromosome painting. FXS was previously reported to accompany sex chromosome aneuploidies; however, to the best of our knowledge, the present patient is the first FXS patient with an aberration involving autosomes. He contributes to the current knowledge on monosomy 21 phenotype, having dysmorphic facial findings despite the concurrent phenotypic expression of the FXS. As a last conclusion, cytogenetic analysis must be done to all mentally retarded patients with minor dysmorphic features.

Distal partial trisomy 1q: report of two cases and a review of the literature.

We report on two cases with partial trisomy 1q syndrome. One case was a mid-trimester fetus with multiple malformations that was prenatally diagnosed with a de novo distal partial trisomy 1q. Prenatal ultrasound at 24th gestational week demonstrated the presence of cleft lip and palate, increased biparietal diameter and decreased abdominal circumference. Cytogenetic analysis (GTG banding) and subsequent fluorescence in situ hybridization (FISH) using whole chromosome paint 1 and multicolor banding (MCB) demonstrated an aberrant karyotype 46,XY,dup(1)(q31q43 approximately 44). The second case was a newborn male infant with multiple congenital malformations. He had a derivative chromosome 18 as a result of a maternal insertion involving chromosomes 1 and 18. Further analyses including MCB showed his karyotype as 46,XY,ins(18;1)(q22;q23q31.1 approximately 32). The present cases and a review of the literature suggest that partial trisomy of the long arm of chromosome 1 is a distinct clinical entity.

A multidisciplinary approach to the management of individuals with fragile X syndrome.

BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Since the identification of the responsible gene (FMR1) and its protein (FMRP), there has been enormous progress in both clinical and pathogenetic research on the neurobehavioural aspects of the condition. However, studies regarding other medical problems anticipated in individuals with FXS are limited. A multidisciplinary study evaluating various causes of morbidity in the same group has not been published yet. METHODS: Twenty-four boys with FXS full mutation were recruited out of a larger group of 103 diagnosed in one centre over the past 10 years. Ear nose and throat, eye and cardiac examinations were performed in addition to routine cognitive, behavioural, neurological and speech and language assessments. RESULTS: The average IQ score was 49.8 +/- 20 (range 25-90). There were four patients (18%) with IQ above 70. Using DSM-IV, attention deficit hyperactivity disorder was diagnosed in five boys out of 22 examined (23%), while 32% were diagnosed with pervasive developmental disorder. The seizure frequency was 17%. A psychiatric disorder was diagnosed in six out of eight boys with electroencephalogram abnormalities (75%). Minimal conductive hearing loss was found in five (5/22) patients. There was significant delay in both expressive and receptive language skills. Ocular findings were refractive errors (13%) and strabismus (4.4%). Mitral valve prolapsus (MVP) was observed in 3/22 (13.7%) patients and aortic annulus dilatation was present in 2/22 (9%) patients. CONCLUSIONS: Frequency of psychiatric diagnoses made with DSM-IV were in parallel to those reported in the literature. Comorbidity of seizures and psychiatric disorders was noteworthy. The percentage of 'high-functioning' full mutation males supports the previous observations. Ear nose and throat and eye examination revealed remarkably lower prevalence of abnormal findings than reported. MVP was slightly less frequent compared with the single study in the literature. Age at the time of examination had an effect on the outcome of cardiac evaluation. These findings will guide us in future management of the group of patients followed in our institution. The protocol applied provides an applicable outline for multidisciplinary institutional settings dealing with individuals with FXS.

CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial carcinoma.

The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for endometrial hyperplasia (EH) and endometrial carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and ECa and control subjects using allele-specific polymerase chain reaction-based method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with EH, indicating that persons carrying any Val allele are at increased risk for developing EH. In the ECa group, patients were also more likely to have CYP1A1 Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a statistically significant increase in relative risk association with any Val genotype between patients and controls, suggesting that individuals carrying any Val genotype are at increased risk for developing ECa. We concluded that variant alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility. Further studies with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.

Thermolabile methylenetetrahydrofolate reductase enzyme genotype is frequent in type 2 diabetic patients with normal fasting homocysteine levels.

OBJECTIVE: To investigate the plasma homocysteine concentrations with regard to nutritional, metabolic and genetic factors and to find out the frequency and impact of thermolabile methylenetetrahydrofolate reductase (T-MTHFR) polymorphism in patients with type 2 diabetes mellitus. DESIGN: A cross-sectional study. SUBJECTS: A total of 94 subjects with type 2 diabetes mellitus and 91 healthy age- and sex-matched nonsmoking volunteers were recruited. MAIN OUTCOME MEASURES: Age, sex, duration and complications of diabetes mellitus, metabolic variables, fasting plasma homocysteine levels, and presence of T-MTHFR polymorphism were evaluated for all participants. Presence of T-MTHFR polymorphism was analysed to define any possible role in diabetes progress, complications and metabolic milieu. RESULTS: Fasting homocysteine levels were similar in diabetic patients and controls. Prevalence of homozygous polymorphism of thermolabile MTHFR gene (TT) was encountered more frequently in patients with diabetes mellitus than the healthy controls (P = 0.004). Subgrouping of the patients with respect to MTHFR genotype revealed similar metabolic variables and frequency of chronic complications of diabetes mellitus in groups. Patients with TT genotype revealed longer diabetes duration when compared with the patients having heterozygous mutation of thermolabile MTHFR or normal homozygous MTHFR genotypes (P = 0.046). CONCLUSIONS: Type 2 diabetic patients have similar fasting plasma homocysteine levels with that of age- and sex-matched healthy people. There is no correlation between diabetic complications and this amino acid metabolite. On the contrary, thermolabile variant of MTHFR genotype is found to be more frequent in diabetic patients especially in those who have experienced a longer duration of disease.

Prenatal diagnosis of laryngeal atresia.

Prenatal diagnosis of congenital atresia of the larynx is difficult but is possible by the findings of increased lung echogenicity and size coexisting with fetal ascites in ultrasonography. Sonographic findings may not always be typical. We report on a case of congenital laryngeal atresia diagnosed prenatally by the findings of fetal hydrops and hyperechogenic lungs. Our case presented with oligohydramnios. We also review syndromes that demonstrate laryngeal anomalies.

Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together /=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.

Tumour necrosis factor alpha G-->A -238 and G-->A -308 polymorphisms in juvenile idiopathic arthritis.

OBJECTIVES: To study G-->A -238 and G-->A -308 polymorphisms in the promoter region of the tumour necrosis factor (TNF) alpha gene in patients with juvenile idiopathic arthritis (JIA). We analysed whether there were any associations between these polymorphisms and the type of JIA and/or the clinical course of the disease in two populations. METHODS: The first group consisted of 51 Turkish JIA patients and the second consisted of 159 JIA patients from the Czech Republic. Healthy individuals (93 and 100) from each country served as controls. Subgroups of JIA were defined according to the Durban criteria. The course of the disease was defined on the basis of the physician's global evaluation of disease activity, the swollen and tender joint count and the erythrocyte sedimentation rate. RESULTS: In both JIA cohorts, the distribution of genotypes was not significantly different among the types of JIA. The G-->A -238 polymorphism did not have an effect on the patients' outcome in either group. The G-->A -308 polymorphism was significantly associated with a poor outcome in the Turkish group (P=0.005) but there was no association in the Czech patients. Some features of JIA in Turkish patients differed from those in Czech patients. CONCLUSIONS: Genetic differences may accompany the phenotypic differences found in the Turkish group. Although larger numbers of patients are clearly needed to verify this, we suggest that the G-->A -308 polymorphism may be operative in defining disease outcome in selected groups.

Evaluation of children with myelodysplastic syndrome: importance of extramedullary disease as a presenting symptom.

Thirty-three children diagnosed with primary myelodysplastic syndrome (MDS) in a single institution over an 8 year period were evaluated with special emphasis on children who presented with extramedullary disease (EMD). EMD was present at diagnosis in 12 (36%) of the 33 children with MDS. Three patients with juvenile myelomonocytic leukemia (JMML) and 2 patients with chronic myelomonocytic leukemia (CMML) presented with pleural effusion. Pericardial effusion was present in 3 of these patients, two of whom also had thrombosis. Pyoderma gangrenosum, relapsing polychondritis were the initial findings in another two cases with JMML. Lymphadenopathy (n=1), gingival hypertrophy (n=2), orbital granulocytic sarcoma (n=1) and spinal mass (n=1) were the presenting findings in 5 patients with refractory anemia with excess of blasts in transformation. Since high-dose methylprednisolone (HDMP, 20-30 mg/kg/day) has been shown to induce differentiation and apoptosis of myeloid leukemic cells in children with different morphological subtypes of acute myeloid leukemia in vivo and in vitro, 25 children with de novo MDS were treated with combined HDMP and cytotoxic chemotherapy. Dramatic improvement of EMD and decrease in blast cells both in the peripheral blood and bone marrow were obtained following administration of short-course HDMP treatment alone as observed in children with AML. HDMP, combined with low-dose cytosine arabinoside and mitoxantrone were used for the remission induction. Remission was achieved in 8 (80%) of 10 children who presented with EMD and in 9 (60%) of 15 children without EMD. Long-term remission (>6 years) was obtained in 4 (two with JMML and two with CMML), three of whom presented with EMD. In conclusion EMD can be a presenting finding in childhood MDS as observed in adults. In addition, the beneficial effect of HDMP combined with more intensive chemotherapy should be explored as alternative therapy in children with MDS not suitable for bone marrow transplantation.

Chromosomal mosaicism in a pregnant woman treated with acyclovir for herpes simplex encephalitis.

At 17th week of pregnancy, a 28-year-old woman was diagnosed as having herpes simplex encephalitis and treated with intravenous acyclovir. Follow-up by the serial ultrasound examinations, intrauterine growth retardation (IUGR) was found. During the course of disease, cordocentesis was performed to evaluate the risk of the disease and the infant's chromosomal constitution. No herpes simplex virus infection on cord blood sample was observed; however, chromosomal analysis revealed: 46,XX/47,XX,+2/47,XX,+11/47,XX,+19/48,XX,+11. After termination of pregnancy, the fetus was found as having ventricular septum defect. The presence of the triploid cell lines mocaicism involving chromosome 2 and 19 were confirmed by the analysis of fetal skin tissues. No attributable finding to herpes simplex virus infection and acyclovir treatment was found, and the presence of the triploid cell lines mocaicism were appeared to be purely coincidental.

Tetrasomy 8 as a primary chromosomal abnormality in a child with acute megakaryoblastic leukemia. a case report and review of the literature.

Tetrasomy 8 is a relatively rare chromosomal abnormality in hematological disorders, and is mostly associated with myeloid malignancies and poor prognosis. In a number of cases, tetrasomy 8 has been reported as an accompanying anomaly with other chromosomal changes. In this report, we describe a 14-year-old girl with acute megakaryoblastic leukemia associated with tetrasomy 8 (primary) and trisomy 6, 19 and 20. She died 6 months after diagnosis, suggesting a relatively poor prognosis for AML with tetrasomy 8. To the best of our knowledge, this is the first report of a tetrasomy 8 abnormality associated with subtype FAB M7. Interestingly, this abnormality has not been previously reported in childhood AML patients.

Glutathione S-transferase M1 gene polymorphism in bladder cancer patients. a marker for invasive bladder cancer?

The glutathione S-transferase M1 (GSTM1) gene is polymorphic in humans, and the deficiency in enzyme activity of GSTM1 is caused by the inherited homozygous absence of the GSTM1 gene, or the "null" genotype (GSTM1, 0/0). The increased risk of bladder cancer has been shown to correspond with this gene defect. No reports, however, have been found in the literature regarding GSTM1 gene deficiency with superficial and invasive bladder cancer. In this study, we examined the association of the GSTM1-null genotype with superficial and invasive bladder cancer. Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the GSTM1 gene defect in Turkish patients with superficial bladder cancer (N = 61), invasive bladder cancer (N = 42), and control subjects (N = 202) who had no history of cancer. The GSTM1 null genotype was observed in 34.7% of the control subjects and in 54.3% of total bladder cancer patients (OR: 2.246; 95% CI: 1.384-3.645, P: 0.00094). In other words, the presence of the GSTM1-null genotype significantly increased the risk of bladder cancer development. Among invasive bladder cancers, the frequency of the GSTM1-null genotype was 64.3% (OR: 0.294, 95% CI: 0.147-0.590, P: 0.0003). This was also significantly higher than control subjects, indicating that patients carrying this genotype were at increased risk for developing invasive bladder cancer. This relationship was not statistically significant in the superficial bladder cancer group (OR: 0.585, 95% CI: 0.327-1.045, P: 0.06). Our results indicate that GSTM1 gene polymorphism should be considered as an important risk modifier in the development of bladder cancer and might be used as a predictive marker for invasive bladder cancer.

Clinical outcomes of consanguineous marriages in Turkey.

Turkey has a high rate of consanguineous marriages. Different nationwide surveys indicate that today 20-25% of marriages are consanguineous, with the rate having increased over the last 15 years. The results of many studies show that the rate of consanguinity among parents of children with rare recessive diseases is quite above Turkey's average and that the high consanguinity rate is one of the underlying factors of high infant and child mortality and fertility in Turkey.

Microdeletion of 22q11 (CATCH 22) in children with conotruncal heart defect and extracardiac malformations.

CATCH 22 is a medical acronym for cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcemia, and a variable deletion on chromosome 22q11. The deletion within the chromosome region of 22q11 may occur in patients with dysmorphologic and cardiological syndromes: DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), and conotruncal anomaly face syndrome (CAFS). In this study, using N25 (D22S75) DiGeorge chromosome region probe. fluorescence in situ hybridization (FISH) analyses were performed on 32 patients with congenital heart diseases. Twenty-nine of 32 patients had conotruncal heart disease. A 22q11 deletion was detected in two patients (6.9%) of the 29 patients with conotruncal heart disease. One of our 22qdel (+) patients had unilateral facial nerve palsy. Although it is not a frequent finding, unilateral facial nerve palsy will be included among the symptoms of CATCH 22 syndrome. After careful clinical evaluation of patients with conotruncal cardiac anomalies, only syndromic cases should be screened for this deletion.