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San Giovanni Rotondo, Italy

Ozen S.,Pediatric Endocrinology Unit | Aldemir O.,Medical Genetic Unit
Genetic Counseling | Year: 2012

The patient is a 2.8 years old male who is extremely obese and severe hyperphagic from birth. He had seizures attacks and apnea from the second week of his life. He has red hair and serum cortisol and ACTH levels are very low. We examined our patient as a hypocortisolism due to ACTH deficiency and central hypothyrodism. After the corticosteroid replacement therapy hair color changed to brown. We performed molecular genetic analysis at the Institue for Experimental Pediatric Endocrinology laboratory in Berlin, Germany by Krude H. and found compound heterozygous mutations. As a result the case is diagnosed as POMC deficiency. Source

Paciorkowski A.R.,Washington University in St. Louis | Thio L.L.,Washington University in St. Louis | Thio L.L.,Pediatric Epilepsy Center | Rosenfeld J.A.,Signature | And 18 more authors.
European Journal of Human Genetics | Year: 2011

Infantile spasms (ISS) are an epilepsy disorder frequently associated with severe developmental outcome and have diverse genetic etiologies. We ascertained 11 subjects with ISS and novel copy number variants (CNVs) and combined these with a new cohort with deletion 1p36 and ISS, and additional published patients with ISS and other chromosomal abnormalities. Using bioinformatics tools, we analyzed the gene content of these CNVs for enrichment in pathways of pathogenesis. Several important findings emerged. First, the gene content was enriched for the gene regulatory network involved in ventral forebrain development. Second, genes in pathways of synaptic function were overrepresented, significantly those involved in synaptic vesicle transport. Evidence also suggested roles for GABAergic synapses and the postsynaptic density. Third, we confirm the association of ISS with duplication of 14q12 and maternally inherited duplication of 15q11q13, and report the association with duplication of 21q21. We also present a patient with ISS and deletion 7q11.3 not involving MAGI2. Finally, we provide evidence that ISS in deletion 1p36 may be associated with deletion of KLHL17 and expand the epilepsy phenotype in that syndrome to include early infantile epileptic encephalopathy. Several of the identified pathways share functional links, and abnormalities of forebrain synaptic growth and function may form a common biologic mechanism underlying both ISS and autism. This study demonstrates a novel approach to the study of gene content in subjects with ISS and copy number variation, and contributes further evidence to support specific pathways of pathogenesis. © 2011 Macmillan Publishers Limited All rights reserved. Source

Margari L.,University of Bari | Lamanna A.L.,University of Bari | Craig F.,University of Bari | Simone M.,University of Bari | Gentile M.,Medical Genetic Unit
European Journal of Pediatrics | Year: 2014

Abnormalities of the sex chromosomes (47, XXY, 47 XYY, 45,X/46,XY mosaicism) are frequently associated with Autism Spectrum Disorders (ASD), but the male predisposition to these disorders has not been clearly explained. Previously, the role of the X chromosome was considered important in the ASD mainly because autistic symptoms were detected in genetic syndromes involving X chromosome (fragile X syndrome, Rett syndrome, Klinefelter syndrome). Instead, few studies have analyzed the possible role of the Y chromosome in the ASD. This study explores the role of the Y chromosome in ASD through a systematic literature review about the association between ASD and XYY syndrome and a description of two new cases with this association. The literature review considered studies published in peer-reviewed journals, included in the MEDLINE and PubMed databases, that examined the association between ASD and XYY syndrome. Few studies reported the occurrence of ASD in children with XYY karyotype and the majority of them did not reported a well-defined autism diagnostic category associated with an extra Y chromosome, but several clinical conditions that are generically described as language and social impairment. Conclusion: This study underlines the underestimated role of the Y chromosome in ASD, and we postulate that all the ASD associated with the XYY karyotype may presumably fall within mild degree of ASD as in our cases. © 2014 Springer-Verlag Berlin Heidelberg. Source

Stagi S.,University of Florence | Lapi E.,University of Florence | Cecchi C.,University of Florence | Chiarelli F.,University of Chieti Pescara | And 3 more authors.
Hormone Research in Paediatrics | Year: 2014

Background: In adults with Williams-Beuren syndrome (WBS), a common endocrine abnormality is type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). However, few and sporadic data are available in children, adolescents, and young adults with WBS. Aim: To evaluate the frequency of IGT and T2DM in a cohort of children and young patients with WBS. Patients and Methods: We longitudinally evaluated 27 patients (9 males and 18 females, median age at study onset 13.6 years) with WBS. The median follow-up was 3.6 years. Variables of insulin resistance and β-cell function were evaluated in all subjects using an oral glucose tolerance test. The homeostasis model assessment (HOMA) of insulin resistance and the Matsuda index of insulin sensitivity were calculated. The study of the GCK and HNF1α genes was performed in patients with glucose metabolism abnormalities. 45 age- and sex-matched healthy subjects and 51 age-, sex- and BMI-matched subjects were recruited as two control groups. Results: Considering nutritional status, 7 (25.9%) patients were obese, 9 (33.3%) overweight, and 11 (40.8%) normal-weight. One (3.1%) patient had acanthosis nigricans. IGT was diagnosed in 7 (25.9%) WBS patients and T2DM in 3 (11.1%). Considering all WBS patients, the median value of HOMA was 5.23 (range 2.93-14.89; insulin 24.73 ± 14.67 μU/ml; glucose 104.98 ± 16.06 mg/dl). Considering BMI values, HOMA was 11.00 (range 6.53-12.56), 5.64 (range 3.54-7.95), and 4.54 (range 3.21-5.43), and insulin was 34.53 ± 6.84, 22.76 ± 8.91, and 19.47 ± 6.01 μU/ml in obese, overweight, and normal-weight WBS patients, respectively. Comparing the results with the two control groups, WBS patients showed higher insulin values than healthy controls (p < 0.001), but similar values as the BMI-matched control group (p = n.s.). However, WBS patients showed significantly higher values of glycemia (healthy control group, p < 0.001; BMI-matched control group, p < 0.05) and HOMA (healthy control group, p < 0.001; BMI-matched control group, p < 0.05) than the two control groups. Finally, among WBS patients there was a higher number of subjects with IGT and T2DM than among healthy controls (p < 0.0001) and the BMI-matched control group (p = 0.0002). Conclusion: Our data strongly suggest that IGT and T2DM may be frequently discovered in children, adolescents, and young adults with WBS. WBS should be included among the genetic syndromes associated with T2DM. Further studies are necessary to evaluate the etiopathogenesis of this aspect. © 2014 S. Karger AG, Basel. Source

Bedeschi M.F.,Medical Genetic Unit | Colombo L.,University of Milan | Mari F.,University of Siena | Hofmann K.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 5 more authors.
Molecular Syndromology | Year: 2011

Van den Ende-Gupta syndrome (VDEGS) is a congenital condition characterized by craniofacial and skeletal manifestations, specifically blepharophimosis, malar and maxillary hypoplasia, distinctive nose, arachnocamptodactyly, and long slender bones of the hands and feet. To date, only 24 patients have been described. It is generally thought that the syndrome is transmitted by an autosomal recessive mode of inheritance, although evidence for genetic heterogeneity has recently been presented. We report on a girl followed from birth up to 3 years of life with a set of peculiar minor anomalies, arachnocamptodactyly of hands and feet, characteristic of VDEGS in association with a 22q11.12 deletion. Recently, the VDEGS gene was mapped to the DiGeorge syndrome region on 22q11.2, and homozygous mutations in the SCARF2 gene were identified. We now report the first patient with VDEGS due to compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 splice site mutation. Copyright © 2011 S. Karger AG, Basel. Source

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