DiGeorge anomaly in a patient with isochromosome 18p born to a diabetic mother

The DiGeorge anomaly (DGA) is an etiologically heterogeneous developmental field defect in which cardiovascular malformations, hypocalcemia, thymic hypoplasia, and characteristic dysmorphisms are major clinical features. The 22q11.2 deletion is the most common single etiology of DGA, although a number of other chromosomal abnormalities and teratogens, including maternal diabetes, have been implicated as well. We present a patient, born to a diabetic mother, with interrupted aortic arch type B (IAA‐B), neonatal hypocalcemia, thymic hypoplasia, and dysmorphic features including microcephaly, thick, overfolded helices, and anteriorly‐placed anus. Cytogenetic studies showed the presence of a marker chromosome, identified by fluorescence in‐situ hybridization (FISH) as an isochromosome 18p [i(18p)]. We did not detect a 22q11.2 deletion by FISH using a cosmid probe corresponding to locus D22S75. The patient is the first example of either DGA or IAA‐B in a patient with i(18p). We review the genetic abnormalities associated with DGA, and discuss the potential contributions of maternal diabetes and i(18p) in our patient. © 2005 Wiley‐Liss, Inc.

[1]  J. Fryns,et al.  Partial trisomy 1, karyotype 46,XY,12-,t(1q, 12p)+ , 1973, Humangenetik.

[2]  A. Schinzel.  Catalogue of Unbalanced Chromosome Aberrations in Man, 2nd Edition , 2004, Chromosome Research.

[3]  A. Chapelle,et al.  A deletion in chromosome 22 can cause digeorge syndrome , 2004, Human Genetics.

[4]  R. Abu-sulaiman,et al.  Congenital Heart Disease in Infants of Diabetic Mothers: Echocardiographic Study , 2004, Pediatric Cardiology.

[5]  S. Minoshima,et al.  Role of TBX1 in human del22q11.2 syndrome , 2003, The Lancet.

[6]  P. Pradat,et al.  The Epidemiology of Cardiovascular Defects, Part I: A Study Based on Data from Three Large Registries of Congenital Malformations , 2003, Pediatric Cardiology.

[7]  P. Pradat,et al.  The Epidemiology of Cardiovascular Defects, Part 2: A Study Based on Data from Three Large Registries of Congenital Malformations , 2003, Pediatric Cardiology.

[8]  J. Graham,et al.  Infants of diabetic mothers are at increased risk for the oculo-auriculo-vertebral sequence: A case-based and case-control approach. , 2002, The Journal of pediatrics.

[9]  C. Loffredo,et al.  Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants. , 2001, Teratology.

[10]  W. Robinson,et al.  Grandmaternal origin of an isochromosome 18p present in two maternal half-sisters. , 2001, American journal of medical genetics.

[11]  C. Loffredo,et al.  Interrupted aortic arch: an epidemiologic study. , 2000, Teratology.

[12]  K. Tokel,et al.  Occurrence of an aortic arch anomaly in two siblings born to a diabetic mother. , 2000, The Turkish journal of pediatrics.

[13]  B. Emanuel,et al.  Characterization of 10p deletions suggests two nonoverlapping regions contribute to the DiGeorge syndrome phenotype. , 1998, American journal of human genetics.

[14]  J. Towbin,et al.  A genetic etiology for interruption of the aortic arch type B. , 1997, The American journal of cardiology.

[15]  G. Sholler,et al.  Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13--implications for cytogenetics and molecular biology. , 1996, American journal of medical genetics.

[16]  C. Pignata,et al.  Progressive deficiencies in blood T cells associated with a 10p12-13 interstitial deletion. , 1996, Clinical immunology and immunopathology.

[17]  M. Digilio,et al.  Maternal diabetes causing DiGeorge anomaly and renal agenesis. , 1995, American journal of medical genetics.

[18]  W. Schempp,et al.  De novo isochromosome 18p in two patients: cytogenetic diagnosis and confirmation by chromosome painting , 1994, Clinical genetics.

[19]  R. Novak,et al.  Coincident DiGeorge anomaly and renal agenesis and its relation to maternal diabetes. , 1994, American journal of medical genetics.

[20]  E. Berry-Kravis,et al.  Two patients with overlapping de novo duplications of the long arm of chromosome 9, including one case with Di George sequence. , 1994, American journal of medical genetics.

[21]  B. Emanuel,et al.  DiGeorge anomaly with renal agenesis in infants of mothers with diabetes. , 1993, American journal of medical genetics.

[22]  J. Kirklin.  Coarctation of the aorta and interrupted aortic arch , 1993 .

[23]  J. Dumanski,et al.  Molecular genetic study of the frequency of monosomy 22q11 in DiGeorge syndrome. , 1992, American journal of human genetics.

[24]  B. Emanuel,et al.  A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. , 1992, American journal of human genetics.

[25]  V. Park,et al.  Diagnosis of tetrasomy 18p using in situ hybridization of a DNA probe to metaphase chromosomes. , 1991, American journal of medical genetics.

[26]  E. Blennow,et al.  Molecular identification of a small supernumerary marker chromosome by in situ hybridization: diagnosis of an isochromosome 18p with probe L1.84 , 1991, Clinical genetics.

[27]  C. Pignata,et al.  DiGeorge anomaly associated with 10p deletion. , 1991, American journal of medical genetics.

[28]  E. Haan,et al.  The isochromosome 18p syndrome: confirmation of cytogenetic diagnosis in nine cases by in situ hybridization. , 1990, American journal of human genetics.

[29]  R. McCarter,et al.  Maternal diabetes and cardiovascular malformations: predominance of double outlet right ventricle and truncus arteriosus. , 1990, Teratology.

[30]  M. Khoury,et al.  Clinical-epidemiologic assessment of pattern of birth defects associated with human teratogens: application to diabetic embryopathy. , 1989, Pediatrics.

[31]  L. W. Perry,et al.  Congenital cardiovascular malformations associated with chromosome abnormalities: an epidemiologic study. , 1989, The Journal of pediatrics.

[32]  D. Ledbetter,et al.  Cytogenetic findings in a prospective series of patients with DiGeorge anomaly. , 1988, American journal of human genetics.

[33]  D. Ledbetter,et al.  Prenatal diagnosis of deletion 17p13 associated with DiGeorge anomaly. , 1988, American journal of medical genetics.

[34]  D. Ledbetter,et al.  Hypoparathyroidism and T cell immune defect in a patient with 10p deletion syndrome. , 1986, The Journal of pediatrics.

[35]  J. Opitz,et al.  The DiGeorge anomaly as a developmental field defect. , 1986, American journal of medical genetics. Supplement.

[36]  P. Fernhoff,et al.  Retinoic acid embryopathy. , 1985, The New England journal of medicine.

[37]  A. Schinzel,et al.  Catalogue of Unbalanced Chromosome Aberrations in Man , 1985 .

[38]  E. Stiehm,et al.  The DiGeorge syndrome and the fetal alcohol syndrome. , 1982, American journal of diseases of children.

[39]  E. Zackai,et al.  The association of the DiGeorge anomalad with partial monosomy of chromosome 22. , 1982, The Journal of pediatrics.

[40]  G. Verellen,et al.  Association of bilateral renal agenesis and Di George syndrome in an infant of a diabetic mother. , 1982, Helvetica paediatrica acta.

[41]  M. Taylor,et al.  Multiple congenital anomalies, thymic dysplasia, severe congenital heart disease, and oligosyndactyly with a deletion of the short arm of chromosome 5. , 1981, American journal of medical genetics.

[42]  J. F. Mancer,et al.  The spectrum of the DiGeorge syndrome. , 1979, The Journal of pediatrics.

[43]  P. L. Townes,et al.  Inherited Partial Trisomy 8q (22 → qter) , 1978 .

[44]  F. O. Black,et al.  Aural abnormalities in partial DiGeorge syndrome. , 1975, Archives of otolaryngology.

[45]  L. Pinsky,et al.  A link between Turner syndrome in the male and Turner syndrome in the female with normal chromosomes , 1965 .

[46]  M. Cooper,et al.  A new concept of the cellular basis of immunity , 1965 .