Kahvecioglu D, Atasay B, Berberoglu M
… +10 more, Yildiz D, Cakir U, Akduman H, Erdeve O, Siklar Z, Magdelaine C, Lienhardt-Roussie A, Akar M, Ozbek MN, Arsan S
Martínez-Barrera LE, Morán-Barroso VF, Perezpeña-Díazconti M
… +3 more, Zuñiga-Rodríguez FG, Manzano-Sierra C, García-Delgado C
Genet Couns
· 2014 · PMID 25365855
Escobar syndrome (ES) or multiple pterygia syndrome (MIM#265000) is an infrequent condition characterized by facial dysmorphism, multiple webbing (pterygia), congenital contractures (arthrogryposis) and other internal an...Escobar syndrome (ES) or multiple pterygia syndrome (MIM#265000) is an infrequent condition characterized by facial dysmorphism, multiple webbing (pterygia), congenital contractures (arthrogryposis) and other internal anomalies. We describe an 8-days-old male newborn from consanguineous parents with ES who also presented heterotaxia syndrome and esophageal atresia, anomalies that not have been previously reported as associated to ES.
Zeidler S, Oudesluijs GG, Schoonderwaldt EM
… +1 more, Van Bever Y
Genet Couns
· 2014 · PMID 25365854
Disruption in early pregnancy can cause severe and multiple congenital anomalies in a foetus. Three sequences, Limb-body wall complex (LBWC), amniotic band sequence (ABS) and body-stalk anomaly (BSA) are thought to be ca...Disruption in early pregnancy can cause severe and multiple congenital anomalies in a foetus. Three sequences, Limb-body wall complex (LBWC), amniotic band sequence (ABS) and body-stalk anomaly (BSA) are thought to be caused by disruption. This case report describes a foetus with severe multiple congenital anomalies, that fit the diagnoses of all three sequences, which might advocate these syndromes are a spectrum of one sequence.
Eyüpoğlu FC, Sünnetçi D, Cine N
… +4 more, Savli H, Okten A, Açikgöz EG, Sönmez FM
Genet Couns
· 2014 · PMID 25365853
Small supernumerary ring chromosomes (sSRC) represent a subset of small supernumerary marker chromosomes (sSMC) where r(8) is relatively common. The phenotype sSRC(8) ranges from almost normal to variable degrees of abno...Small supernumerary ring chromosomes (sSRC) represent a subset of small supernumerary marker chromosomes (sSMC) where r(8) is relatively common. The phenotype sSRC(8) ranges from almost normal to variable degrees of abnormalities in mosaic or non-mosaic conditions. We present a new patient of de novo mosaic supernumerary ring chromosome 8 which has trisomy of a region of chromosome 8p11.21-q21.13. Mosaicism for a ring chromosome was showed by routine karyotyping that revealed a karyotype of mos47,XY,+r(?) [47]/46,XY [36] and we performed array comparative genomic hybridization (array-CGH) in order to precisely define the extension about chromosomal origin of the duplicated region in a patient. Array-CGH analysis confirmed that the sSRC derived a 43.921 Mb genomic gain of chromosome 8 (p11.21-q21.13). Common clinical features of the patient included multiple congenital anomalies, developmental delay, thoracolumbar scoliosis, mild pulmonary stenosis, laryngomalacia, hypospadias and atypical facial appearance. With this study a patient involving mosaic trisomy 8p11.21-q21.13 along with clinical properties, is described and compared to previously reported cases involving partial trisomy 8q.
Zorlu P, Eksioglu AS, Ozkan M
… +2 more, Tos T, Senel S
Genet Couns
· 2014 · PMID 25365852
Wolf-Hirschhorn syndrome is caused by a deletion of the distal portion of the short arm of chromosome 4, and is characterized by psychomotor retardation, seizures, congenital malformations, and typical facial appearance...Wolf-Hirschhorn syndrome is caused by a deletion of the distal portion of the short arm of chromosome 4, and is characterized by psychomotor retardation, seizures, congenital malformations, and typical facial appearance including 'Greek warrior helmet' appearance of the nose. The form and the severity of clinical manifestations vary according to the size and location of the deletion. Major complications are severe growth retardation, developmental delay, seizures, feeding difficulties due to hypotonia, and predisposition to respiratory infections. Patients will benefit from supportive therapy and special education. It is important in terms of prognosis to provide counseling to families in this respect. We present here a case with Wolf-Hirschhorn Syndrome in order to remind its rarity and the ability of the patients' progress in the areas of motor skills, speech, social interaction.
Brambila-Tapia AJ, Neira VA, Vásquez-Velásquez AI
… +5 more, Jimenez-Arredondo RE, Chávez-González EL, Picos-Cárdenas VJ, Fletes-Rayas AL, Figuera LE
Genet Couns
· 2014 · PMID 25365851
The 9p trisomy is a relatively frequent disorder, while pure 9p trisomies are less frequent and usually derived from 9;22 translocations, duplications or 9p extra chromosomes. Here we report a patient with pure trisomy 9...The 9p trisomy is a relatively frequent disorder, while pure 9p trisomies are less frequent and usually derived from 9;22 translocations, duplications or 9p extra chromosomes. Here we report a patient with pure trisomy 9p derived from a terminal balanced unreciprocal translocation. The patient derived to the genetic service by psychomotor delay, presented at 2 years and 11 months: short stature, open anterior fontanelle, dysplastic ears, facial dysmorphisms, long and broad first toes with hypoplastic nails, central nervous system and skeletal alterations. The patient karyotype was: 46,XY,der(10)t(9;10) (p13.1;qter)mat while the mother karyotype was: 46,XX,t(9;10)(p13.1;qter). The presence of the subtelomeric region of 10q showed by FISH as well as the duplication of 9p subtelomere was further confirmed with multiplex ligation dependent probe amplification (MLPA) for the subtelomeric region of all chromosomes. The mechanism of formation seems to be due to a telomere break in 10q leading to loss of telomeric functions, permitting the 9p fusion; this has been supported with molecular probes showing telomere shortening in interstitial telomeric repeats, which are unable to prevent chromosome fusion. This is one of the few cases reported with terminal translocations (not jumping) preserving the subtelomeric region and highlights the importance of subtelomeric probes in terminal arrangements, and the utility of molecular probes, such as MLPA in defining this kind of abnormalities. In the clinical context, the patient presented a high proportion of 9p trisomy features which is expected considering the large 9p segment involved and the presence of the critical region 9p22.
Here we describe clinical and cytogenetic data on a female child whom had been referred to our laboratory suspected to have Turner syndrome since she had webbed neck. Cytogenetic analysis revealed that she had deletion a...Here we describe clinical and cytogenetic data on a female child whom had been referred to our laboratory suspected to have Turner syndrome since she had webbed neck. Cytogenetic analysis revealed that she had deletion at 11q23.2 to 11q terminal so her karyotype was ascertained as 46,XX,del(11)(q23.2). Her parents had normal karyotypes. In addition to many clinical features of del(11q ) syndrome the case had poor vision which is not common for this syndrome. Clinical features of this case and a few published cases will be reviewed briefly.
Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene and has three phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in newborns, failure to thrive...Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene and has three phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in newborns, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) in older children, and recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2) in adults. NICCD presents in the first few weeks of life with cholestatic hepatitis syndrome, multiple aminoacidemia and hypergalactosemia. To date almost all reported patients were from East Asia and only few cases from Caucasian origin have been described. We report the first Bulgarian case of NICCD. Mutation screening of the SLC25A13 gene revealed the compound heterozygous mutations c.1081C>T (p.R361*) and c.74C>A (p. A25E) which confirmed the diagnosis of NICCD. The nonsense mutation c.1081C>T (p.R361*) is novel.
Puvabanditsin S, Memon N, Chekmareva M
… +2 more, Di Stefano V, Mehta R
Genet Couns
· 2014 · PMID 25365848
We report a neonate with prenatal ultrasound imaging features suggestive of CLOVES syndrome, confirmed postnatally by clinical and imaging findings of the constellation of truncal overgrowth, cutaneous capillary malforma...We report a neonate with prenatal ultrasound imaging features suggestive of CLOVES syndrome, confirmed postnatally by clinical and imaging findings of the constellation of truncal overgrowth, cutaneous capillary malformations, lymphatic and musculoskeletal anomalies. The clinical, radiological and histopathological findings noted in our patient help differentiate from other overgrowth syndromes such as Proteus syndrome. We report perinatal findings and add new clinical findings of this rare syndrome.
The aim of this study was to present the first case with Down syndrome in conjunction with de novo isochromosomes of both short and long arm of the chromosome 21. Cytogenetics, molecular cytogenetics and molecular geneti...The aim of this study was to present the first case with Down syndrome in conjunction with de novo isochromosomes of both short and long arm of the chromosome 21. Cytogenetics, molecular cytogenetics and molecular genetic analysis were performed on chorionic villus sampling at 12 weeks of gestation of a 42-years-old pregnant woman. According to cytogenetics, molecular cytogenetics and molecular genetic analysis the karyotype was designated as: 47,XY,i(21) (qter --> q10::q10 --> qter),+i(21) (pter --> p10::p10 --> 10pter).ish i(21)(qter --> q10::q10 --> qter)(CEP13/21+,WCP21+),+i(21) (pter --> p10::p10 --> pter)(CEP13/21+,WCP21+). Quantitative Fluorescent Polymerase Chain Reaction (QF-PCR) analysis revealed that isochromosome 21q was maternal in origin. After the detailed genetic counseling, the family decided termination of the pregnancy. This is the first report of co-existence of an isochromosome 21p and an isochromosome 21q in a case with Down syndrome. Our case shows the importance of the molecular cytogenetics and molecular genetic analysis in cases with isochromosomes of the acrocentric chromosomes and supernumerary marker chromosomes regarding to highlight of the formation mechanisms of co-existence of these two rearrangements.
Hemihyperplasia-multiple lipomatosis syndrome (HMLS) is characterized by subcutaneous lipomatosis and an asymmetric overgrowth (hemihyperplasia). We report an extremely rare case of HMLS associated with hydrocephalus, em...Hemihyperplasia-multiple lipomatosis syndrome (HMLS) is characterized by subcutaneous lipomatosis and an asymmetric overgrowth (hemihyperplasia). We report an extremely rare case of HMLS associated with hydrocephalus, emphasizing the clinical features and differential diagnosis.
The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal...The VATER/VACTERL association is typically defined by the presence of at least three of the following congenital malformations: vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, and limb abnormalities (13). We report a rare case of a monochorionic twin gestation in which one of the infants had VACTERL association. Antenatal ultrasound showed bilateral renal dysplasia and cardiac anomaly (ASD) in twin A. Twin A was noted to have the following anomalies: a single umbilical artery, limb anomaly (right hand preaxial polydactyly), vertebral anomalies (T9 and T11 butterfly vertebras, bilateral renal agenesis, bladder agenesis, anal and urethral atresia. A normal-sized stomach and normal amount of amniotic fluid were observed during the prenatal period with no other anomalies. Twin B (male) was healthy and no cardiac, renal, or congenital anomalies were demonstrated on ultrasound and physical examination. Infant A was also diagnosed as having VACTERL association because he had five of the core anomalies (V, A, C, R, L) of VACTERL association. Butterfly vertebra is an uncommon congenital spinal anomaly. To the best of our knowledge, our patient is the second case VACTERL association with butterfly vertebra in the literature.
Pariltay E, Durmaz A, Durmaz B
… +6 more, Aykut A, Onay H, Ak H, Aydin HH, Ozkinay F, Cogulu O
Genet Couns
· 2014 · PMID 25059023
New array technologies have facilitated the analysis of submicroscopic chromosomal imbalances and structural variants. Copy number variation (CNV) analysis can reveal genetic imbalances in up to 10% of cases involving in...New array technologies have facilitated the analysis of submicroscopic chromosomal imbalances and structural variants. Copy number variation (CNV) analysis can reveal genetic imbalances in up to 10% of cases involving intellectual disability (ID), with or without multiple congenital anomalies (MCA). Here we present 4 cases, diagnosed by CNV analysis using Affymetrix Genome Wide Human SNP 6.0 array, and their parents. CNVs ranging from 18 to 196 per subject, with a size range of 100kb- 6093kb, were detected in all cases. One case revealed inherited CNVs, whilst de novo ins/dels were found in the other three which may be causative factors in the development of clinical pictures. Microarray technology may help to reveal the etiology of ID and is a potentially useful diagnostic tool for patients with ID/MCA.
Klinefelter syndrome (KS) is a common sex chromosome disorder and is characterized by small, firm testes with hyalinization of the seminiferous tubules, elevated gonadotropins and azoospermia. Among karyotypic variants o...Klinefelter syndrome (KS) is a common sex chromosome disorder and is characterized by small, firm testes with hyalinization of the seminiferous tubules, elevated gonadotropins and azoospermia. Among karyotypic variants of KS, mosaicism 47,XXY/46,XX is extremely rare. We report here a case of an 18-year-old boy with a mosaic 47,XXY/46,XX karyotype of peripheral blood diagnosed as KS. The boy presented with anterior mediastinal mass which was confirmed as combined carvenous lymphangioma and mixed germ cell tumor by histologic examination of resected tissue. He had the male phenotype, however, azoospermia was incidentally detected on sperm banking analysis, performed prior to chemotherapy for mixed germ cell tumor. He had small and firm testes, mild gynecomastia, collectively tanner stage IV, mild hypergonadotropic hypogonadism and no evidence of true hermaphroditism. This report presents a rare case of mosaicism 47,XXY/46,XX karyotype in a phenotypic male with KS and mediastinal germ cell tumors. Based on what we experienced and review of the literature, cytogenetic analysis is recommended when physicians are confronted with a young patient with mediastinal germ cell tumor.
Kavurt S, Celik IH, Ada BS
… +2 more, Bas AY, Demirel N
Genet Couns
· 2014 · PMID 25059021
Down syndrome (DS), trisomy 21, is the most common numerical chromosome abnormality among live born infants. Dysmorphic features, congenital malformations, cognitive impairment are major features. Musculoskeletal anomali...Down syndrome (DS), trisomy 21, is the most common numerical chromosome abnormality among live born infants. Dysmorphic features, congenital malformations, cognitive impairment are major features. Musculoskeletal anomalies are associated with abnormal collagen function. Ectrodactyly is characterized by a deep median cleft of the hand and/or foot. Failure of apical ectodermal ridge while developing limbs leads to ectrodactyly. Here we report a patient diagnosed with DS and ectrodactyly which were split between the third and fourth fingers and there were 4 fingers on both hands. There was no additional musculoskeletal anomaly. Karyotype analysis revealed 47,XY,+21. To the best of our knowledge our patient is the first patient with DS and ectrodactyly. Pathogenesis ofmusculoskeletal anomalies in DS and ectrodactyly seems to be different which may be coincidental or not. In conclusion, patients with ectrodactyly should be evaluated for association with syndromes, and it should be kept in mind that patients with Down syndrome may have different organ anomaly from frequently seen anomalies.
De Keyzer L, De Leenheer EM, Claes K
… +1 more, Janssens S
Genet Couns
· 2014 · PMID 25059020
Birt-Hogg Dubé syndrome is an autosomal dominant disease with variable clinical expression. It is characterized by cutaneous manifestations, renal tumors and lung cysts. Other tumors, such as adrenal tumors and tumors or...Birt-Hogg Dubé syndrome is an autosomal dominant disease with variable clinical expression. It is characterized by cutaneous manifestations, renal tumors and lung cysts. Other tumors, such as adrenal tumors and tumors originating from the neural crest cells such as meningioma and neurothekeoma have also been described. This syndrome is caused by germline mutations in the folliculin (FLCN) gene located on chromosome 17p. We report, for the first time, a patient with BHDS and a history of a vestibular schwannoma in adolescence. The diagnosis of BHDS was confirmed, by identifying a nonsense mutation in exon 10 of the FLCN gene. A vestibular schwannoma also originates from neural crest cells, just as other neural tumors, previously encountered in patients with BHDS. The reported mutations cause a truncation of the protein, folliculin. The exact role of folliculin is still undetermined. Two different theories suggest the effect of tumorigenesis. One is that folliculin plays an important role in the AMPK-mTOR pathway which leads to proliferation of cells when activated. The other is that the folliculin acts as a possible tumor suppressor gene, since there is a high frequency of second hits in the FLCN-gene. In order to confirm a possible relation of BHDS and neural crest tumors, further research is necessary in the tumorigenesis of the folliculin gene.