Partial trisomy of chromosome 5 was first described by Lejeune et al. in 1964 on the short arm (12). The vast majority of the partial trisomy 5 cases include 5p duplications; however we reported a small supernumerary mar...Partial trisomy of chromosome 5 was first described by Lejeune et al. in 1964 on the short arm (12). The vast majority of the partial trisomy 5 cases include 5p duplications; however we reported a small supernumerary marker chromosome. General symptoms include developmental delay, mental retardation, seizures, respiratory difficulties, congenital heart defects, abdominal muscle hypoplasia and dysmorphic features such as macrocephaly, enlarged anterior fontanelle, dolichocephaly, upslanting palpebral fissures, epicanthal folds, hypertelorism, abnormal ears, midface hypoplasia, short nose, broad nasal bridge and microretrognathia. Arachnodactyly and club foot may be seen as cytoskeletal abnormalities and, hypotonia may be determined in neurological exam. Here we reported a case with developmental delay, attention deficit hyperactivity disorder, mild mental retardation and dysmorphic features, caused by a new small supernumerary marker chromosome, generating partial trisomy 5pI 2-q 11.2. To our knowledge, this small supernumerary marker chromosome has not been reported before. Severe type of partial trisomy 5 includes seizures, congenital heart defects, hypotonia and failure to thrive. Previously reported partial trisomy 5 cases, who showed severe phenotype, had usually duplicated 5p13 region. Therefore, patients, who do not have duplicated 5p13, showed mild phenotype. Also, duplication of the long arm of chromosome 5, may contribute to the milder phenotype and the longer survival in partial trisomy 5 patients. Attention deficit hyperactivity disorder, which we described in the present case, may be a result of partial trisomy 5, because it includes ADHD4 gene. This case may help better understanding the karyotype/phenotype correlation related to partial trisomy 5.
Okur M, Eroz R, Bektas MS
… +4 more, Gulsen S, Bahadir A, Turker Y, Gunes C
Genet Couns
· 2016 · PMID 30204958
The aim of the study was to compare the effects of three eNOS gene polymorphisms associated with congenital heart defects, between Down syndrome patients with and without cardiac anomalies. Transthoracic echocardiographi...The aim of the study was to compare the effects of three eNOS gene polymorphisms associated with congenital heart defects, between Down syndrome patients with and without cardiac anomalies. Transthoracic echocardiographic examinations and eNOS single-nucleotide polymorphisms were investigated on seventy-five patients, prospectively. The frequencies of mutant alleles in the eNOS promoter (the -786T/C polymorphism) and exon 7 mutant alleles (the 894G--->T polymorphism) were significantly higher in Down syndrome patients with and without cardiac anomalies. The frequency of the intron GIOT polymorphism did not significantly differ between patients with and without cardiac anomalies. We found a significant relationship between eNOS gene polymorphisms and the congenital heart defects in patients with Down syndrome. Screening for the presence or absence of eNOS polymorphisms may be useful to obtain preliminary data on the risk of congenital heart defects in patients with Down syndrome.
Niemann-Pick disease (NPD) type B is a lysosomal storage disorder caused by a deficiency of acid sphingomyelinase (ASM). We report the clinical follow-up of a 16-year-old Mexican mestizo woman with a NPD type B phenotype...Niemann-Pick disease (NPD) type B is a lysosomal storage disorder caused by a deficiency of acid sphingomyelinase (ASM). We report the clinical follow-up of a 16-year-old Mexican mestizo woman with a NPD type B phenotype who presented hepatosplenomegaly, persitstenly low high-density lipoprotein (HDL) cholesterol and thrombocytopenia, without central nervous system involvement. After of a dengue fever episode with severe anemia and pancytopenia, leading to a bone marrow study n which foamy histiocytes were noticed and diagnosis of NiemannPick disease was suspected; and confirmed by biochemical and molecular tests. The missense c.1343 A>G (p.Tyr448Cys, formerly Y446C) and c. 1426C>T (p.Arg476Trp, formerly R474W) mutations in the SMPD1 gene were identified. These mutations have never been reported in the Mexican population. Since the c.1343 A>G (Y446C) mutation has been previously reported in a Japanese patient with NPD type A, we suggest an attenuator effect of c.1426C>T (R474W) allele (previously associated with the NPD type B phenotype). In conclusion, this is the first description of the concomitant occurrence of Y446C and R476W mutations in a Mexican patient with NPD type B, showing the importance of increased awareness and availability of specialized diagnostic tests in the diagnosis of rare inherited metabolic diseases.
Nur BG, Clark OA, Cetin Z
… +3 more, Toylu A, Karauzum SB, Mihci E
Genet Couns
· 2016 · PMID 29485826
Isochromosome 18p is a rare chromosomal disorder that occurs with a frequency of approximately one in every 180,000 live births, and affects both genders equally. MOst cases result from a de novo formation. In the litera...Isochromosome 18p is a rare chromosomal disorder that occurs with a frequency of approximately one in every 180,000 live births, and affects both genders equally. MOst cases result from a de novo formation. In the literature, there are currently only a small number of reports that describe the phenotypic and clinical features of Isochromosome 18p. In this article, we report six cases that displayed the phenotypic and clinical features of Isochromosome 18p, and which were subsequently confirmed by conventional karyotyping and fluorescence in situ hybridization. We also discuss the clinical features of these patients in the context of the cases previously reported in the literature.
Hanhart Syndrome (OMIM 103300) is an extremely rare syndrome with some congenital malformations. It is characterized by hypoglossia, adactylia/hypodactylia, peromelia of arms and/or legs and micrognathia. The severity of...Hanhart Syndrome (OMIM 103300) is an extremely rare syndrome with some congenital malformations. It is characterized by hypoglossia, adactylia/hypodactylia, peromelia of arms and/or legs and micrognathia. The severity of the symptoms can differ from patient to patient. Some affected individuals may have only a part of these clinical features. In this case report, we want to present a Turkish girl with hypoglossia, micrognathia and peromelia who was diagnosed according to the clinical and radiographic findings.
VACTERL association includes vertebral anomalies, anal atresia, cardiac defects, tracheao-esophageal fistula, renal anomalies, and limb abnormalities. It is defined by the presence of at least three of these congenital m...VACTERL association includes vertebral anomalies, anal atresia, cardiac defects, tracheao-esophageal fistula, renal anomalies, and limb abnormalities. It is defined by the presence of at least three of these congenital malformations. The incidence has been estimated to be 1/10.000-1/40.000 live births. We report on a preterm infant with VACTERL presentin with respiratory complicatons due to the presence of severe tracheomalacia and bronchomalacia. He also had an annular pancreas.
Selim L, Van Coster R, Mehaney D
… +11 more, Hassan F, Vanlander A, Smet J, De Latter E, Vandemeulebroecke K, Mohamed Abdou D, Nakhla G, Mostafa M, Habets D, Bakker J, Abdel Bary A
Genet Couns
· 2016 · PMID 29485812
BACKGROUND: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare autosomal recessive disorder. The disease is caused by mutations in the thymidine phosphorylase gene. This article reports the clinical, b...BACKGROUND: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare autosomal recessive disorder. The disease is caused by mutations in the thymidine phosphorylase gene. This article reports the clinical, biochemical and molecular findings in three Egyptian patients with Mitochondrial Neurogastrointestinal Encephalopathy sundrome from two different pedigrees. SUBJECTS AND METHODS: The three patients were subjected to thorough neurologic examination. Brain Magtnetic Resonance Imaging. Histochemical and biochemical assay of the mitochondrial respiratory chain complexes in muscle homogenate was performed (1/3). Thymidine Phosphorylase enzyme activity was performed in 2/3 patients and Thymidine Phosphorylase gene sequencing was done (2/3) to confirm the diagnosis. RESULTS: All patients presented with symptoms of severe gastrointestinal dysmotility with progressive cachexia, neuropathy, sensory neural hearing loss, asymptomatic leukoencephalopathy. Histochemical analysis of themuscle biopsy revealed deficient cytochrome C oxidase and mitochrondrial respiratory chain enzyme assay revealed isolated complex 1 deficiency (1/3). Thymidine Phosphorylase enzyme activity revealed complete absence of enzyme activity in 2/3 patients. Direct sequencing of Thymidine Phosphorylase gene revealed c.3371 A>C homozygous mutation. Molecular screening of both families revealed heterozygous mutation in both parents and 4 siblings. CONCLUSIONS: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare mitochondrial disorder with an important diagnostic delay. In case of pathogenic mutations in Thymidine Phosphorylase gene in the family, carrier testing and prenatal diagmosis of at risk members is recommended for early detection. The possibility of new therapeutic options makes it necessary to diagnose the disease in an early state.
Vohwinkel syndrome (VS), also known as keratoderma hereditaria mutilans, is a rare keratinization genetic disorder characterized by palmoplantar keratoderma, skeletal dysmorphisms and varying degrees of sensorineural dea...Vohwinkel syndrome (VS), also known as keratoderma hereditaria mutilans, is a rare keratinization genetic disorder characterized by palmoplantar keratoderma, skeletal dysmorphisms and varying degrees of sensorineural deafness. Its mode of inheritance is autosomal-dominant, with mutations in loricrin and connexin 26 (GJB2) genes that manifest during infancy and boceme more evident during adulthood. We herein report a case of VS in a 23-year-old female exhibiting sensorineural hearing loss, palmar keratoderma and homozygous deletion mutation delE120 (c.358-360delGAG) in the GJB2 gene. VS, is a rare genetic disorder, should be considered in patients with palmoplantar keratoderma and hearing loss and should be investigated connexin 26 (GJB2) gene mutation.
Lurie IW, Novikova IV, Tarletskaya OA
… +2 more, Lazarevich AA, Gromyko OA
Genet Couns
· 2016 · PMID 29485808
We present a fetus with typical manifestations of distal monosomy 13q (oligodactyly, heart defect, anal atresia, hypoplastic kidneys) and der( 13)t( 1 ; 13)(q42;q21)pat. He also had exencephaly which at this developmenta...We present a fetus with typical manifestations of distal monosomy 13q (oligodactyly, heart defect, anal atresia, hypoplastic kidneys) and der( 13)t( 1 ; 13)(q42;q21)pat. He also had exencephaly which at this developmental stage is an embryological precursor of anencephaly. Detailed analysis of neural tube defects (NTD) in publications about distal monosomy 13q showed that most defects affect cranial aspect of the neural tube (anencephaly, exencephaly, encephaloceles) with a relative small proportion of spina bifida. There are strong evidences that the gene(s) responsible for the origin of NTD in distal monosomy 13q has to be located within 13q33q34 segments. However, our analysis showed that NTD are much more common for the patients (fetuses) having larger deletions (with breakpoints at 13q22 or more proximal). These data suggest that the 13q22 segment includes a regulatory element somehow controlling function of the "distal" NTD-related gene(s).