Browsing by Author "Phadke, Shubha R"

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    Aarskog syndrome.
    (2002-04-27) Chaddha, Vandana; Phadke, Shubha R
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    Aetiologic spectrum of mental retardation & developmental delay in India.
    (2012-09) Aggarwal, Shagun; Bogula, Vijay Raju; Mandal, Kausik; Kumar, Rashmi; Phadke, Shubha R
    Background & objectives: The aetiology of mental retardation is varied and difficult to establish. Reports from India on the spectrum of underlying causative conditions are lacking. This retrospective study was conducted to establish the various aetiologies of mental retardation (MR) and developmental delay (DD) in patients attending a medical genetics centre in north India and to assess the contribution of genetic disorders. Methods: This retrospective study was conducted at a tertiary care centre in north India. All patients attending the centre with MR or DD from January 2007 to December 2009 were included. The aetiology of MR/DD was ascertained after clinical assessment and targeted laboratory evaluation. The spectrum of causative conditions and contribution of genetic disorders was established. Results: A total of 338 patients were included in the study, of whom definite diagnosis was established in 253 (74.8%). The various aetiological categories were: chromosomal disorders in 112 (33.1%), non chromosomal syndromes in 32 (9.5%), neurometabolic disorders in 34 (10.1%), central nervous system structural defects in 25 (7.4%), cerebral palsy in 43 (12.7%) and environmental insults in 7 (2%). Eighty five patients (25.2%) had idiopathic mental retardation. A total of 196 (58%) patients had a genetic disorder as the cause of MR/DD. Interpretation & conclusions: The aetiology of MR/DD is varied and difficult to establish in a significant proportion of patients. Chromosomal and various monogenic disorders contribute to a large number of MR/DD cases and hence a genetic work up is essential for all such patients.
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    Anotia and facial palsy: unusual features of cardiofacial syndrome.
    (2005-06-30) Girisha, K M; Phadke, Shubha R
    The authors report a child with features of Cardiofacial syndrome with anotia and facial paralysis. This is the first report of such an association.
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    Asphyxiating thoracic dystrophy with facial dysmorphism.
    (2006-12-05) Sankar, V H; Phadke, Shubha R
    Here it is reported a male newborn baby with features of asphyxiating thoracic dystrophy (ATD) with facial dysmorphism. The disproportionate rhizomelic short stature, narrow thorax, long fibulae, wide metaphysis and trident acetabule are consistent with diagnosis of ATD. In addition the baby had facial dysmorphism and broad thumbs and great toes similar to Oto-palato-digital syndrome type II (OPD II). The association of these features with ATD is not reported till date.
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    Basal ganglia changes: a diagnostic clue to Sandhoff disease.
    (2006-10-03) Girisha, K M; Phadke, Shubha R
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    Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients.
    (2014-01) Boggula, Vijay R; Shukla, Anju; Danda, Sumita; Hariharan, Sankar V; Nampoothiri, Sheela; Kumar, Rashmi; Phadke, Shubha R
    Background & objectives: Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many microdeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. Methods: A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fl uorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. Results: The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Interpretation & conclusions: Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID.
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    Computer-aided Facial Analysis in Diagnosing Dysmorphic Syndromes in Indian Children
    (Indian Academy of Pediatrics, 2019-12) Narayanan, Dhanya Lakshmi; Ranganath, Prajnya; Aggarwal, Shagun; Dalal, Ashwin; Phadke, Shubha R; Mandal, Kaushik
    Objective: To assess the utility of computer-aided facial analysis in identifying dysmorphicsyndromes in Indian children. Methods: Fifty-one patients with a definite molecular orcytogenetic diagnosis and recognizable facial dysmorphism were enrolled in the study andtheir facial photographs were uploaded in the Face2Gene software. The results provided bythe software were compared with the molecular diagnosis. Results: Of the 51 patients, thesoftware predicted the correct diagnosis in 37 patients (72.5%); predicted as the first in thetop ten suggestions in 26 (70.2%). In 14 patients, the software did not suggest a correctdiagnosis. Conclusions: Computer-aided facial analysis is a method that can aid indiagnosis of genetic syndromes in Indian children. As more clinicians start to use thissoftware, its accuracy is expected to improve.
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    Cytochrome P450 (CYP2C9*2,*3) & vitamin-K epoxide reductase complex (VKORC1 -1639G
    (2013-01) Kaur, Anupriya; Khan, Farah; Agrawal, Suraksha S; Kapoor, Aditya; Agarwal, Surendra K; Phadke, Shubha R
    Background & objectives: Studies have demonstrated the effect of CYP2C9 (cytochrome P450) and VKORC1 (vitamin K epoxide reductase complex) gene polymorphisms on the dose of acenocoumarol. The data from India about these gene polymorphisms and their effects on acenocoumarol dose are scarce. The aim of this study was to determine the occurrence of CYP2C9*2,*3 and VKORC 1 -1639G>A gene polymorphisms and to study their effects on the dose of acenocoumarol required to maintain a target International Normalized Ratio (INR) in patients with mechanical heart valve replacement. Methods: Patients from the anticoagulation clinic of a tertiary care hospital in north India were studied. The anticoagulation profile, INR (International Normalized Ratio) values and administered acenocoumarol dose were obtained from the clinical records of patients. Determination of the CYP2C9*2,*3 and VKORC1 -1639G>A genotypes was done by PCR-RFLP (restriction fragment length polymorphism). Results: A total of 111 patients were studied. The genotype frequencies of CYP2C9 *1/*1,*1/*2,*1/*3 were as 0.883, 0.072, 0.036 and that of VKORC1 -1639G>A for GG, AG, and AA genotypes were 0.883, 0.090, and 0.027, respectively. The percentage of patients carrying any of the variant alleles of CYP2C9 and VKORC1 in heterozygous or homozygous form was 34% among those receiving a low dose of ≤20 mg/wk while it was 13.8 per cent in those receiving >20 mg/wk (P=0.014). A tendency of lower dose requirements was seen among carriers of the studied polymorphisms. There was considerable variability in the dose requirements of patients with and without variant alleles. Interpretation & conclusions: The study findings point towards the role of CYP2C9 and VKORC1 gene polymorphisms in determining the inter-individual dose variability of acenocoumarol in the Indian patients with mechanical heart valve replacement.
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    Delleman syndrome.
    (2006-02-11) Patil, S J; Phadke, Shubha R
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    Diagnosing acrocallosal syndrome.
    (2003-02-29) Gupta, Ashutosh; Thakur, Seema; Phadke, Shubha R
    A 3-month-old male child presented with typical features of acrocallosal syndrome. He satisfies Courten's diagnostic criteria for acrocallosal syndrome.
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    Diagnosis and Management of Gaucher Disease in India – Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics
    (Indian Academy of Pediatrics, 2018-02) Puri, Ratna Dua; Kapoor, Seema; Kishnani, Priya S; Dalal, Ashwin; Gupta, Neerja; Muranjan, Mamta; Phadke, Shubha R; Sachdeva, Anupam; Verma, Ishwar C; K, Pramod
    Justification: Gaucher disease (GD) is amongst the most frequently occurring lysosomal storage disorder in all ethnicities. The clinicalmanifestations and natural history of GD is highly heterogeneous with extreme geographic and ethnic variations. The literature on GD haspaucity of information and optimal management guidelines for Indian patients.Process: Gaucher Disease Task Force was formed under the auspices of the Society for Indian Academy of Medical Genetics. Invitedexperts from various specialties formulated guidelines for the management of patients with GD. A writing committee was formed andthe draft guidelines were circulated by email to all members for comments and inputs. The guidelines were finalized in December 2016at the annual meeting of the Indian Academy of Medical Genetics.Objectives: These guidelines are intended to serve as a standard framework for treating physicians and the health care systems foroptimal management of Gaucher disease in India and to define unique needs of this patient population.Recommendations: Manifestations of GD are protean and a high index of suspicion is essential for timely diagnosis. Patients frequentlyexperience diagnostic delays during which severe irreversible complications occur. Leucocyte acid ?-glucosidase activity ismandatory for establishing the diagnosis of Gaucher disease; molecular testing can help identify patients at risk of neuronopathicdisease. Enzyme replacement therapy for type 1 and type 3 Gaucher disease is the standard of care. Best outcomes are achieved byearly initiation of therapy before onset of irreversible complications. However, in setting of progressive neurological symptoms such asseizures and or/ neuroregression, ERT is not recommended, as it cannot cross the blood brain barrier. The recommendations herein arefor diagnosis, for initiation of therapy, therapeutic goals, monitoring and follow up of patients. We highlight that prevention of recurrenceof the disease through genetic counseling and prenatal diagnosis is essential in India, due to uniformly severe phenotypes encounteredin our population
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    Exome sequencing & homozygosity mapping for identification of genetic aetiology for spastic ataxia in a consanguineous family.
    (2015-08) Dalal, Ashwin; Bhowmik, Aneek D; Agarwa, Divyal; Phadke, Shubha R
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    Fabry disease: A treatable lysosomal storage disorder.
    (2009-01) Phadke, Shubha R; Mandal, Kausik; Girisha, K M
    Fabry disease is a lysosomal storage disease with an X-linked inheritance pattern, which presents in childhood as acroparaesthesias. Its non-specific symptoms often lead to delays in the diagnosis. We report the case of a 13-year-old boy who presented with typical acroparaesthesia of Fabry disease, his younger brother had gastrointestinal manifestations of the disease and their mother’s symptoms suggested that she is a carrier. Enzyme replacement therapy helped in ameliorating the patient’s symptoms and preventing complications such as renal failure, stroke and cardiovascular disorders.
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    Feasibility of thalassaemia control by extended family screening in Indian context.
    (2002-03-23) Saxena, Anita; Phadke, Shubha R
    Thalassaemia is one of the most common genetic disorders in India. Its control is possible by screening of general population for carrier status and by antenatal diagnosis in couples at risk of having a child with thalassaemia. This study explored the feasibility of screening the extended family to detect carriers to prevent birth of thalassaemic children and identified the barriers to its acceptance. One hundred parents with thalassaemic child on a regular hypertransfusion programme were interviewed using a pre-designed questionnaire. The results showed that 96% of them were more willing to share information on their thalassaemic children with relatives and friends. Relatives of 62 parents accepted the risk of being a carrier, and 14 families got themselves tested for it so far. Another 34 families could not get themselves tested due to non-availability of screening facilities in the nearby town, high cost of the test, and lack of sufficient motivation. It is concluded that, by and large, parents have no reservations in sharing information on their affected children with their relatives, but the communication needs to be improved for all families to accept the risk of having a thalassaemic child. There is also a need to make the screening more readily available and to motivate high-risk groups through awareness-raising programmes.
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    Genetic counseling.
    (2004-02-01) Phadke, Shubha R
    Genetic counseling is a process of communicating medical aspects about a genetic disorder, especially the information regarding risk of occurrence as recurrence of the disease in the family and preventive options. Accurate diagnosis of the affected member is of paramount importance for genetic counseling. Special genetic investigations like DNA analysis and chromosomal analysis are essential for many cases and especially when prenatal diagnosis is necessary. It is essential for pediatricians to identify cases with genetic disorders or possibly genetic disorders. These cases should be adequately worked up to identify accurate etiology as far as possible. The investigations should be done even if they are not going to make any difference in the outcome of the child. The genetic disorders present not only in neonates, but also in children, stillbirths and fetuses. Hence, autopsy of stillbirth and fetuses terminated after prenatal diagnosis is essential for genetic counseling. The importance of genetic counseling as an integral part of management of genetic disorders has to be realized by all clinicians. Pediatricians with short training can take over the responsibility of providing counseling for common genetic disorders and may need to refer others to genetic centre for counseling and prenatal diagnosis.
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    Genetic counseling: the impact in Indian milieu.
    (2004-12-05) Phadke, Shubha R; Pandey, Amita; Puri, Ratna Dua; Patil, S J
    OBJECTIVE: To assess the impact of genetic counseling in Indian milieu. METHODS: A study of 83 Indian consultants who were provided genetic counseling was carried out to understand their expectations, satisfaction with genetic counseling and its effects on reproductive decision. RESULTS: Most of the families were referred for the diagnosis and the treatment of the disorder in the proband. The consultants understood the medical facts about risk of recurrence and were satisfied with genetic counseling. There was no change in reproductive plan after genetic counseling in most of the cases. CONCLUSION: The reproductive decision was mainly correlating with the presence or absence of normal live children in the family and availability of prenatal diagnosis.
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    Hemihyperplasia syndromes.
    (2006-07-01) Dalal, Ashwin B; Phadke, Shubha R; Pradhan, Mandakini; Sharda, Sheetal
    OBJECTIVE: Hemihyperplasia is a heterogenous group of disorders characterized by asymmetric limb growth. There is considerable confusion regarding their classification and ascertainment into various syndromes. We tried to look into the various aspects of hemihyperplasia syndromes. METHODS: Records of 17 consecutive cases of hemihyperplasia were reviewed and were ascertained into various syndromes based on available literature and diagnostic criteria. RESULTS: Of the 17 cases with hemihyperplasia, 3 cases satisfied the diagnostic criteria for Proteus syndrome. One patient each was ascertained as Klippel Trenaunay Weber syndrome and Hemihyperplasia- Multiple lipomatosis. 9 cases were classified as isolated hemihyperplasia. We found two novel associations with hemihyperplasia; namely Ehlers-Danlos syndrome like skin changes and Poland anomaly on the affected side. The remaining 3 cases had miscellaneous disorders with limb asymmetry, namely Neurofibromatosis Type I in 2 cases and Olliers disease in one case. CONCLUSION: Efforts to diagnose syndromes of hemihyperplasia help in genetic counseling.
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    Hunter Syndrome in Northern India: Clinical features and Mutation Spectrum.
    (2016-02) Narayanan, Dhanya Lakshmi; Srivastava, Priyanka; Mandal, Kausik; Gambhir, Poonam Singh; Phadke, Shubha R
    Objective: To study the clinical profile and mutation spectrum of Hunter syndrome. Methods: Evaluation of 18 cases of Hunter syndrome from 17 families was done. Mutation analysis of Iduronate sulfatase (IDS) gene was done in 9 families, and mothers of four affected children with no family history. Results: Joint contracture, hepatomegaly and radiological changes were present in all children. 6 (33%) children had normal cognitive function at presentation. Point mutations were identified in all the 9 families for whom mutation analysis was done. Among 4 mothers tested from families without any family history, 2 (50%) were found to be carriers. Conclusion: Accurate etiological diagnosis by mutation analysis of IDS gene is important in Hunter syndrome.
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    Identification of DKC1 gene mutation in an indian patient.
    (2010-03) Tamhankar, Parag M; Zhao, Meina; Kanegane, Hirokazu; Phadke, Shubha R
    Dyskeratosis congenita - X-linked variety was diagnosed in a twelve year old male child with cutaneous pigmentary changes and dystrophic changes in nails of hands and feet. His elder brother had similar nail changes and had died at twelve yr of age. We demonstrated the A353V mutation in the proband after sequencing the DKC1 gene. The mother was found to be carrier for the same mutation. She did not have any clinical manifestations. This is the commonest mutation worldwide responsible for X-linked variety of this disease and has been demonstrated for the first time in an native Indian patient.