4p trisomy secondary to paternal translocation t(4p-;15q+)

A new case of trisomy 4p is reported. The patient was a boy with dysmorphism, growth failure and developmental retardation. Craniofacial features included microcephaly with a flat forehead, a prominent glabella, hyperteleorism, a broad, concave nasal bridge, a bulb-shaped nose, a wide mouth with a prominent upper lip and a short philtrum, low-set ears, a low hairline, micrognathia, and a short neck. Abdominal muscles were normal. Cryptorchidism with a hypoplastic scrotum and a micropenis were found, as well as forced flexion of the fingers and talipes equinus. The intravenous urogram disclosed ptosis of the right kidney. Developmental retardation was severe with an IQ under 50. RHG banding techniques on peripheral lymphocytes disclosed 4p14 pter duplication. The karyotype was 46,XY inv dup(4-p) (p14----pter). The mother's karyotype was normal. The father had a translocation between the short arm of chromosome 4 and the long arm of chromosome 15; his karyotype was 46,XY, t(4;15) (p14;q26). Thus, the child had trisomy for a segment of the short arm of chromosome 4 (p14----pter) and monosomy for the terminal band of the long arm of chromosome 15 (15q26). The first case of trisomy 4p was reported in 1970 by Wilson et al. Since then, there have been 46 additional reports in the medical literature. Although children with trisomy 4p share a number of features, the phenotypic manifestations of this chromosomal abnormality are variable and nonspecific, making clinical diagnosis difficult.     

Familial XX chromosomal maleness does not arise from a Y chromosomal translocation

To determine the mechanism for the coexistence of XX chromosomal maleness and true hermaphroditism in the same family, we performed cytogenetic and molecular genetic analyses, using DNA probes from the short arm of the Y chromosome. These studies excluded the following possible mechanisms: (1) an inherited, mitotically unstable Y chromosome that results in chromosomal mosaicism, (2) an inherited Y-to-X or Y-autosomal translocation, (3) recurrent Y-to-X translocation, and (4) incomplete inactivation of the X chromosomal homolog for the testicular determining factor. We conclude that the disorder of sexual differentiation observed in this family can be best explained by a dominant autosomal gene with variable expressivity.     

Unusual dysmorphic features in five patients with Noonan's syndrome: a brief review

Noonan's syndrome is a relatively common, multiple congenital anomaly syndrome, genetically inherited as an autosomal dominant disorder with variable penetrance. It is defined by a characteristic phenotype, congenital heart disease, ocular defects and mild mental retardation. Molecular studies have confirmed that it is a heterogeneous disorder and there may be evidence for an autosomal recessive mode of inheritance.1 The gene responsible for Noonan' syndrome has been mapped to the long arm of chromosome 12.2,3 The human deltex gene (DLT x 1), mapping to chromosomal region 12q24 in the vicinity of the Noonan's syndrome critical region is being evaluated as a candidate gene for this disorder.4 Various types of musculoskeletal abnormalities have been reported, including short stature, craniofacial dysmorphism, short or webbed neck and fetal pads in fingers and toes.5 We report five cases with the unusual physical features of overriding toes and simian creases. Such abnormalities can be considered among the minor manifestations of the syndrome.     

Partial trisomy 1 (1q31-41) caused by intrachromosomal insertion in 1p31.3 in a newborn infant and a sister of the mother

Insertions of chromosomal material which are due to 3 breaks are rare events. In this observation a segment of the long arm of chromosome 1q31-41 was shifted to 1p31.3 on the short arm and after recombination had caused trisomy of this segment in 2 cases. Main phenotypical feature is colobomatous microphthalmia. Other traits in which both patients differ considerably are non specific. Any correlation between duplications of the long arm of chromosome 1 and phenotypical expression has not yet been recognized.     

Deletion of the short arm of the X chromosome: A hereditary form of Turner syndrome

In the mothers of two girls with Turner syndrome due to a deletion of the short arm of an X chromosome, the same chromosomal anomaly was detected. Both mothers and daughters had short stature but normal pubertal development. Short parents and normal pubertal development do not exclude Turner syndrome in a girl with small stature.     

Immunodeficiency in a child with partial trisomy 6p

AIM: We present a mentally retarded boy with partial trisomy of the short arm of chromosome 6 as a result of an interstitial tandem duplication of 6p12.2-p21.31 and immunodeficiency. Patients with mental retardation because of a chromosomal disorder or eponymous syndrome often experience recurrent respiratory tract infections as a result of their associated anatomical or neurological abnormalities. However, associated immune defects may also significantly contribute to their susceptibility to infections. Timely recognition and appropriate treatment of their immunodeficiency will greatly improve quality of life in these patients. CONCLUSION: Immunodeficiency may be the direct cause of recurrent respiratory tract infections in patients with mental retardation because of a chromosomal disorder or eponymous syndrome, even in the face of feeding difficulties and multiple episodes of aspiration, as is illustrated in this boy with partial trisomy 6p.     

Autoimmune Thyroiditis in a Case of 18p- Syndrome

A case of a 16-year-old female with autoimmune thyroiditis and a deletion of the short arm of a chromosome 18 (46, xx, 18p-) is described. Evidence for other autoimmune phenomena was also present. The association between this chromosomal aberration and autoimmune disease is reviewed.     

Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion.

The triad of aniridia, ambiguous genitalia, and mental retardation (AGR triad) is the characteristic clinical feature of three unrelated patients with previously unreported chromosome 11 short arm interstitial deletions. A Wilms' tumor in one patient establishes one cause for the aniridia-Wilms' tumor association. The genetic heterogeneity of aniridia, the AGR triad, and Wilms' tumor are demonstrated, and Wilms' tumor is indicated to be a neoplastic birth defect which can result from a variety of embryologic insults, some of which may be chromosomal or heritable.     

A Case of Wolf-Hirschhorn Syndrome and Hypoplastic Left Heart Syndrome

Wolf-Hirschhorn Syndrome (WHS) is a genetic syndrome that includes a typical facial appearance, mental retardation, growth delay, seizures, and congenital cardiac defects. A deletion of the terminal band of the short arm of chromosome 4, with a breakpoint at the 4p15 to 4p16 region, is the most common genetic mutation causing WHS. Congenital heart disease associated with WHS typically includes atrial and ventricular septal defects, though there are a few case reports of associated complex congenital heart disease. Here we report a case of an infant with a large 4p deletion, with a breakpoint at the 4p12 region, and hypoplasic left heart syndrome. We discuss a possible link between the size of the chromosomal deletion in WHS and the severity of the cardiac defect.     

Partial trisomy of chromosome 3 resulting from paternal translocation

The authors report a case of a 3 year-old patient presenting with partial trisomy of the short arm of chromosome 3. According to 21 previously published cases, the main features characterizing this chromosomal abnormality which is mainly observed in males are: cranio-facial dysmorphy, cardiac and genito-urinary malformations, psychomotor retardation. Cytogenetic studies always show an inherited balanced translocation allowing a possible prenatal diagnosis.     

Interstitial deletion of the short arm of chromosome 20 in arteriohepatic dysplasia (Alagille syndrome)

An autosomal dominant transmission of arteriohepatic dysplasia, or Alagille syndrome, with reduced penetrance and variable expressivity has been suggested from familial pedigrees, but the nature of the genetic defect and its chromosomal localization are not firmly established. We report the case of an 8-year-old boy with arteriohepatic dysplasia, in whom high-resolution chromosome study showed a partial deletion of the short arm of chromosome 20, which encompasses subbands p11.23 to p12.3. In situ hybridization and Southern blotting localized four restriction fragment length polymorphism probes within the deletion and another one distal to the deletion. Because one patient has already been reported to have arteriohepatic dysplasia and deletion of the short arm of chromosome 20, and six additional patients with such a deletion had major features of Alagille syndrome, this syndrome should now be assigned to chromosome 20p.     

Characterization of Y chromosomal deoxyribonucleic acid fragments and translocations by Southern blot analysis

Hybridization of Y chromosome-specific probes to Southern blots of genomic deoxyribonucleic acid from patients with chromosomal variants permits direct and rapid characterization of the chromosomal content. We have used two single-copy Y chromosomal sequences specific for the short arm (47z and DP34) and one repeated sequence specific to the long arm (Y3.4) to study several patients with different types of sex chromosomal abnormalities, including three patients with gonadal dysgenesis and the karyotype 45,X/46,X + fragment, two females with Y autosomal translocations involving similar regions of the Y chromosome (46,XX,t(Y;14)(q11,p11) and 46,XY,t(Y;15)(q11,p11), two males with very small Y chromosomes (del(Y)(q12) and i(Yp], and a 45,X male with a small Y autosomal translocation. These techniques are more sensitive than chromosome banding and thus are an important adjunct to karyotyping for analysis of chromosomal content. For patients with gonadal dysgenesis and uncharacterized fragments, demonstration of Y chromosomal sequences identifies an important risk factor for the development of gonadoblastoma. For other patients, accurate identification of Y chromosomal content may facilitate prediction of the patient's phenotype.     

Molecular analysis of patients with Wiedemann-Beckwith syndrome I. Gene dosage on the short arm of chromosome 11

Wiedemann-Beckwith syndrome (WBS) is characterised by a specific group of congenital malformations associated with an increased concurrent risk for development of a defined group of childhood neoplasms. The mode of inheritance is complex, but recently compiled family data suggest that it is an autosomal dominant trait of varying expression. It has previously been suggested that major rearrangements on the short arm of chromosome 11 may be involved in the aetiology of the disease, particularly in the region of the insulin like growth factor II (IGF-II) gene (11p15.5). This gene is thought to be parentally imprinted in the mouse and it has been suggested that in the human, duplication of the non-imprinted locus in WBS patient might lead to diploid expression of the gene and consequent general hyperplasia. This model predicts that there should be both frequent and parental origin specific duplication of the IGF-II gene in the patients. It was the aim of this study to examine the IGF-II locus and its surrounding chromosomal environment for such lesions in a large number of WBS patients. Using restriction fragment length polymorphism analysis for four linked markers on 11p and genomic clones internal to the IGF-II locus we could find no evidence of alteration or amplification of this area in any of the 11 patients investigated. In one patient who developed a Wilms tumour we could find no evidence for loss of any material on the short arm of chromosome 11 as reported previously. We conclude that amplification of genes on the short arm of chromosome 11 is not a frequent occurrence in WBS and certainly not a prerequisite, leaving open the possibility that mutations in unknown transacting factors might affect the expression of IGF-II in these patients in the absence of lesions in the gene itself.     

Calcification of basal ganglia in a patient with partial trisomy 5q and partial monosomy 18q

A patient with partial trisomy for the distal segment of the long arm of chromosome 5 (q35.1 ← qter) with partial 18q monosomy is presented. The mother of the patient was phenotypically normal and was proved to be a carrier of a reciprocal translocation of the long arm of chromosomes 5 and 18 46,XX,t(5;18)(q35.1;q23). The patient shows mild mental retardation, short stature, mild obesity, dysmorphic face, eczema, minor malformations of the extremities, and bilateral intracranial calcification in the basal ganglia. Most of the clinical manifestations of the patient are compatible with the previously reported clinical features of partial trisomy of the distal segment of 5q. However, the calcification of bilateral basal ganglia has not been reported for this chromosomal anomaly.     

Trisomy for the distal end of the short arm of chromosome 3: a syndrome

We report a patient with a chromosomal syndrome involving trisomy for the distal three-fifths of the short arm of chromosome 3. The major clinical featues include bilateral temporal indentation, prominent cheeks, a long and prominent philtrum, protruding middle portion of the upper lip, penile hypoplasia, and an increased number of whorls on digits.     

A novel 1p31.3p32.2 deletion involving the NFIA gene detected by array CGH in a patient with macrocephaly and hypoplasia of the corpus callosum

Interstitial deletions or apparently balanced translocations involving bands 1p31 and 1p32 in the short arm of chromosome 1 are rarely described chromosomal imbalances. To our knowledge, there have been six cases documented to date. Five of these cases, where the NFIA gene is involved, show complex central nervous system malformations and in some cases urinary tract defects. We report another case of a microdeletion with involvement of the NFIA gene in the short arm of chromosome 1 (del(1)(p31.3p32.2)) with, amongst other features, hypoplasia of the corpus callosum, ventriculomegaly, and dysmorphic features. A microdeletion 1p31.3p32.2 which includes the NFIA gene is associated with hypoplasia of the corpus callosum, ventriculomegaly, and dysmorphic features.     

Structural chromosomal anomaly in mental retardation

This article reports the structural chromosomal anomaly in three patients with mental retardation: (i) Proband was a five year old girl with reciprocal retardation (1; 2) (p32; q11) (ii) Proband, female of 14 years. Her karyotype showed translocation (1; 3) (q42; q13). The translocations were de novo in origin (iii) Proband showed variant 13 as the giant satellite over its short arm, and this was paternal in origin. Proband, eighteen months old male child had microcephaly and seizures. These two features may be because of autosomal recessive condition. This report emphasises the need for kayotyping to provide a clear cut diagnosis and appropriate counselling.     

FAMILIAL 4/22 TRANSLOCATION WITH PARTIAL TRISOMY FOR THE SHORT ARM OF CHROMOSOME 4 IN TWO SIBS

ABSTRACT. Sartori, E., Tenconi, R., Baccichetti, C. & Pujatti, G. (Paediatric Clinic, University of Padova, Padova, Italy). Familial 4/22 translocation with partial trisomy for the short arm of chromosome 4 in two sibs. Acta Paediatr Scand 63: 631, 1974.—The further study of subjects, whose abnormal karyotype has been identified by means of the fine analysis of the chromatids with chromosome banding techniques, is necessary for a valid comparison of the clinical patterns. In this paper chromosome banding was carried out by the reverse-staining Giemsa method in the 5 living members of a family with two sibs affected by the same abnormal phenotype. Severe mental retardation, stunted growth, peculiar facies, low-set ears, turricephaly and bilateral hip dislocation or hypoplasia were the main features. The mother and a normal sister had normal karyotype. The father presented a balanced translocation between the short arm of chromosome number 4 and the long arm of chromosome 22. The two malformed children were trisomic for a segment of the short arm of chromosome number 4 (4p14.4pter). The clinical picture observed in these malformed children is quite different from that noted in the only case reported of a child affected by a trisomy for the short arm of chromosome 4 identified by autoradiography alone. This may depend on the different amount of genetic material or on the different chromosome involved in the translocation.     

Patchy white matter hyperintensity in ring chromosome 18 syndrome

Ring chromosome 18 syndrome is a chromosomal abnormality in which partial deletions occur at both ends of chromosome 18, that is, distally on the short and long arms. Previously reported brain magnetic resonance imaging (MRI) abnormalities include diffuse hyperintensity in the white matter, which has been regarded as hypomyelination because the gene for myelin basic protein production is located on the long arm of chromosome 18. We report the case of a 14‐year‐old boy with ring chromosome 18 syndrome, whose MRI showed patchy asymmetrical T2 and fluid‐attenuated inversion‐recovery hyperintensities in the deep white matter as well as diffuse hypomyelination. These patchy lesions may indicate demyelination or gliosis rather than hypomyelination. This result differs from previous reports.     

Interstitial deletions of the short arm of chromosome 4 in a patient with mental retardation and focal seizure

Interstitial deletion of the proximal short arm of chromosome 4 has rarely been described. This defect is associated with variable clinical manifestations, including mental retardation, unusual facial appearance, and minor limb abnormalities. We describe a girl diagnosed with moderate mental retardation and seizures with an interstitial deletion of the short arm of chromosome 4 [46, XX, del(4)(p12p15.2)].