Syndromic encephalocele in a fetal case with a 1p35-pter deletion and a 14q32-qter duplication inherited from a maternal balanced translocation

Occipital encephalocele belongs to the family of neural tube defects, which occur in one among 2000 to 5000 live births. Syndromic encephaloceles include Meckel-Gruber syndrome and various chromosomal abnormalities. We report on a fetal case (13 WG) with bilateral cleft lip and palate, choanal atresia, occipital encephalocele, bilateral club feet, bilateral multicystic kidneys, enlarged bladder and urethral atresia. The fetal chromosome analysis showed a maternally inherited unbalanced translocation between the short arm of chromosome 1 and the long arm of chromosome 14, resulting in 1p35-pter deletion and 14q32-qter duplication (46,XY,der(1),t(1;14)(p35;q32)). Since the chromosomal breakpoints have not previously been implicated in syndromic encephalocele, this observation is of interest for the identification of other genes responsible for occipital encephalocele.     

Phenotypic features of a boy with trisomy of 16q22-->qter due to paternal Y; 16 translocation

We report on the phenotypic features of a patient with partial trisomy of the long arm of chromosome 16 due to an unbalanced Y;16 translocation (46,X,der[Y]t[Y;16] [q12;q22]pat). The patient was noted to have craniofacial anomalies and developmental delay, but no other major malformations. The father, a balanced Y;16 translocation carrier, has apparently normal fertility.     

Large interstitial deletion of chromosome 13q and severe short stature: clinical report and review of the literature

We report a 16 year old African American female with an interstitial deletion of chromosome 13 comprising approximately 40% of the long arm of this chromosome [karyotype 46,XX, del(13)(q14.12q31.2)]. We believe that this case is interesting because of the large size of the chromosome deletion, the severe growth retardation seen in the proband and her prolonged survival.     

A patient with a de novo t (6;9) and an interstitial duplication of (9)(q21.2q22.1).

We report on a 4-year-old child with psychomotor retardation, general hypotonia and only mild dysmorphic features. Her chromosome constitution was 46,XX, t (6;9) (q27;q22.1), dup (9) (q21.2q22.1). This de novo interstitial duplication was confirmed using fluorescence in situ hybridisation (FISH) with band-specific probes. This is the second report of a patient with an interstitial duplication of this region of the long arm of chromosome 9. It is concluded that in a child with an abnormal phenotype and a de novo (apparently) balanced translocation, the possibility of a small duplication or deletion should be considered.     

Tall stature and minor facial dysmorphisms in a patient with a 17.5 Mb interstitial deletion of chromosome 13 (q14.3q21.33): clinical report and review

We present a 4-year-old boy with developmental delay and several into minor dysmorphic features due to an interstitial deletion of 17.5 Mb on the long arm of chromosome 13 [46,XY,del (13)(q14.3q21.33)]. The deletion was detected initially during routine cytogenetic screening and further analyzed on a genome-wide BAC array. In contrast to several previous papers reporting a short stature, our patient was tall with a 1 year advanced skeletal age. In this paper, we compare growth and clinical features of this patient with previously reported cases, with a similar interstitial deletion on the long arm of chromosome 13.     

Abnormalities of chromosome involving 1q in uterine endometrial carcinomas

Cytogenetic studies were performed on endometrial specimens from four patients with hyperplasia, six with adenocarcinoma and one with mixed mesodermal tumor. Except for one cell, all 65 cells from the hyperplastic specimens had a normal female karyotype. However, a total of 92 cells from the 5 adenocarcinoma specimens had chromosomal abnormalities, though all 20 cells from a specimen of a well differentiated adenocarcinoma showed a normal karyotype. The chromosome number and morphology of the aneuploid cells had minimal changes. The modal number of chromosomes was pseudodiploid in one case and hyperdiploid in four. Three kinds of structural abnormalities involving chromosomes 1q were identified as of clonal origin: del. 1 (p21) in 2 cases, t. dic (1;16) (p21;q24) in one case and i (1q) markers in 2 cases. Since the carcinoma cells had two chromosomes 1 of normal morphology, the presence of the marker chromosome led to a partial trisomy or tetrasomy of the long arm of a chromosome 1. This involvement of the long arm of chromosome 1, therefore, may be assumed to represent a karyotypic change in the characteristics of adenocarcinoma of the endometrium. Complex karyotypes with many rearranged chromosomes were observed in cells from the mixed mesodermal tumor. The karyotypic differences between endometrial carcinoma and the mixed mesodermal tumor suggest that the genesis (and its mechanism) of the former may differ from that of the latter.     

Chromosomal 10Q26 trisomy resulting from paternal T(9;10)(PTER;Q26.1).

Distal 10q trisomy is a well defined but rare syndrome, and almost always the result of an unbalanced translocation. Clinical evaluation and cytogenetic molecular analyses were performed in a 6-year-old boy with developmental delay and facial dysmorphism including marked blepharophimosis. His karyotype showed an unbalanced translocation between chromosomes 9 and 10, resulting in trisomy of the distal part of the long arm of chromosome 10q26. A balanced translocation of the segment between chromosomes 9 and 10 with breakpoints at 10q26.1 and 9pter or p24.3 was found in his father, who had normal phenotype. Unlike most cases of partial 10q trisomy which have concurrent partial monosomy of one other translocated chromosome, fluorescence in situ hybridization studies revealed this case to be a pure 10q26 trisomy. The translocated 10q segments in most cases of 10q trisomy originate from the father. Imprinting effect may exist in this chromosomal syndrome; distal 10q trisomy from paternal reciprocal translocations is more compatible with life.     

A family study of complex chromosome rearrangement involving chromosomes 1, 8, and 11 and its reproductive consequences

Complex chromosome translocations are structural chromosomal rearrangements involving three or more chromosomes and more than two breakpoints. A complex chromosome rearrangement was detected in a phenotypically normal female patient that was referred to the hospital for genetic counseling due to reproductive failure. A cytogenetic evaluation was performed, according to standard method of chromosomal analysis, using G-banding technique. The patient’s karyotype showed a balanced complex chromosome rearrangement (BCCR) involving chromosomes 1, 8, and 11 with three breakpoints 1p31, 8q13, and 11q23. The karyotype designed according to ISCN (2013), is 46,XX,t(1;8;11)(p31;q13;q23) (8qter→8q13::1p31→1qter;8pter→8q13::11q23→11qter;11pter→11q23::1p31→1pter). Additionally, the proband’s mother and brother were tested, resulting in the same exact translocation. In this study, we describe all possible meiotic segregations regarding this translocation, as well as the clinical phenotypes which could arise, if unbalanced products of conception survive. This is a rare case of familial complex chromosome rearrangement, giving a view for its reproductive consequences.     

Allelic deletion mapping on chromosome 6q and X chromosome inactivation clonality patterns in cervical intraepithelial neoplasia and invasive carcinoma

OBJECTIVE: Loss of heterozygosity (LOH) profiles and X chromosome inactivation patterns are analyzed in 42 patients with cervical intraepithelial neoplasias (CIN), including low-grade (CIN1) and high-grade (CIN2, CIN3) lesions, and 22 patients with invasive cervical carcinomas. METHOD: Laser capture microdissection was utilized to procure pure matched normal and lesional cells from each case. Sixteen microsatellite markers on four chromosomal arms, 6q21-q25.1, 8p21, 13q12.3--q13, and 17q12--q21, were amplified for LOH, as well as the HUMARA locus for X chromosome inactivation analysis. Eight additional markers spanning the long arm of chromosome 6 were utilized in all cases showing LOH on this arm and in which further tissue material was available for microdissection. RESULTS: Fifty-five percent of carcinomas showed deletions on chromosome bands 6q21--q25.1, 43% on 13q12.3--q13, and 40% on 17q12--q21. Deletions on 6q were identified in CIN3 (40%), CIN2 (37%), and CIN1 (10%), on 13q in CIN3 (33%) and CIN2 (33%), and rarely on chromosomal arm 17q. Finer 6q mapping revealed that marker D6S310 (q22) represented the centromeric and marker D6S255 (q25--q16) the telomeric boundary of deletion. A second, telomeric area of deletion at marker D6S281 (q27) was also identified. Monoclonal X chromosome inactivation patterns were identified in 12/13 cancers, 13/14 CIN3, 5/10 CIN2, and 0/6 CIN1. CONCLUSIONS: Two areas of deletion on chromosome 6q were identified in cervical tumors, suggesting the presence of tumor suppressor gene(s) inactivated in this neoplasia. LOH on this arm were identified early during cervical tumor progression. LOH on 13q and 17q also occur in cervical cancers. X chromosome inactivation patterns suggest that CIN develops into a monoclonal lesion during progression from CIN1 to CIN3.     

Prenatal diagnosis of mosaicism for a del(22)(q13)

A case of prenatally detected mosaicism for a del(22)(q13) is reported. CVS was performed because of abnormal fetal ultrasound findings: cystic 'tumour' in the fetal neck and the upper thoracic aperture. Karyotypes from chorionic villi were suspicious of an aberration concerning the long arm of one chromosome 22. FISH analysis demonstrated mosaicism for a distal 22q deletion in fetal fibroblasts. The deletion was postnatally confirmed by FISH with a chromosome-specific 22q probe. The 'tumour' on autopsy turned out to be cystic thymic tissue. Apart from this, no other obvious fetal anomalies were found.     

Patient with novel interstitial deletion of chromosome 3q13.1q13.3 and agenesis of the corpus callosum

Interstitial deletions of the proximal long arm of chromosome 3 are rare. Only eight previously reported patients have deletions involving the proximal segment of 3q. Of these patients, three had agenesis of the corpus callosum and one had holoprosencephaly. We report here a patient with a small unique interstitial deletion of the long arm of chromosome 3 spanning 3q13.1q13.3. This patient has agenesis of the corpus callosum, global developmental delay, and distinctive facial features of a small nose, anteverted nares, and broad nasal root. Our patient provides further evidence that a gene involved in corpus callosum development or neuronal migration may reside in this region.     

Distal partial trisomy 1q: report of two cases and a review of the literature

We report on two cases with partial trisomy 1q syndrome. One case was a mid-trimester fetus with multiple malformations that was prenatally diagnosed with a de novo distal partial trisomy 1q. Prenatal ultrasound at 24th gestational week demonstrated the presence of cleft lip and palate, increased biparietal diameter and decreased abdominal circumference. Cytogenetic analysis (GTG banding) and subsequent fluorescence in situ hybridization (FISH) using whole chromosome paint 1 and multicolor banding (MCB) demonstrated an aberrant karyotype 46,XY,dup(1)(q31q43 approximately 44). The second case was a newborn male infant with multiple congenital malformations. He had a derivative chromosome 18 as a result of a maternal insertion involving chromosomes 1 and 18. Further analyses including MCB showed his karyotype as 46,XY,ins(18;1)(q22;q23q31.1 approximately 32). The present cases and a review of the literature suggest that partial trisomy of the long arm of chromosome 1 is a distinct clinical entity.     

A patient with de-novo partial deletion of Xp (p11.4-pter) and partial duplication of 22q (q11.2-qter)

We report on a girl with partial deletion of Xp and partial duplication of 22q. Family studies demonstrate that both the patient's mother and her nonidentical twin sister carry the corresponding balanced translocation; 46,X,t(X;22)(p11.4;q11.2). This girl has developmental delay, microcephaly, mild dysmorphisms and hearing loss but otherwise shows few of the features described in individuals with duplications of the long arm of chromosome 22. She does manifest characteristics, such as short stature and biochemical evidence of ovarian failure, which are seen in partial or complete Xp deletions and Turner's syndrome.     

Duplication dup(1)(q32q44) detected by comparative genomic hybridization (CGH): further delineation of trisomies 1q

Partial trisomy 1q is rare and mostly the result of an abnormal segregation of parental translocation chromosomes and their homologues. Only 31 cases have been described with pure partial trisomy 1q. In the fetus presented, chromosome analysis after amniocentesis had shown an unbalanced male karyotype with an aberrant chromosome 1. A de novo terminal duplication of the long arm was suspected but could not be verified by FISH in 1994. Five years after fetal death, retrospective identification of the additional material in 1q could finally be achieved by comparative genomic hybridization (CGH) using DNA extracted from formalin-fixed and paraffin-embedded fetal tissues. A direct duplication dir dup (1)(pter-->q44::q32.1-->qter) was found. Only 6 other individuals with duplication of this segment have been described so far. Comparative delineation of a dup1q phenotype with regard to size and origin of the dup (1q) segment evidenced that large duplications as well as proximal and interstitial duplications coincide with more severe visceral malformations, severe mental retar- dation and a short life span. Terminal duplications (1q32-->qter) concur with less severe malformations and longer periods of survival, but marked mental retardation. With small terminal duplications (1q42-->qter) dysmorphisms are usually mild and intellectual performance is mostly in the normal range.     

Prenatal diagnosis of trisomy 18p and distal 21q22.3 deletion

OBJECTIVES: To present the perinatal findings and molecular cytogenetic analysis of concomitant trisomy 18p (18p11.2-->pter) and distal 21q22.3 deletion. CASE AND METHODS: A 29-year-old woman, gravida 2 para 1, underwent amniocentesis at 17 weeks' gestation because she was a carrier of a balanced reciprocal translocation, 46,XX,t(18;21)(p11.2;q22.3). Cytogenetic analysis of the cultured amniocytes revealed a karyotype of 46,XX,der(21)t(18;21)(p11.2;q22.3). The fetus had a derivative chromosome 21 with an extra short arm of chromosome 18 attached to the terminal region of the long arm of chromosome 21. Level II sonograms did not find prominent structural anomalies. The pregnancy was terminated subsequently. At autopsy, the proband displayed a mild phenotype of hypertelorism, a small mouth, micrognathia, a narrowly arched palate, low-set ears, and clinodactyly. The brain and other organs were unremarkable. Genetic marker analysis showed a distal deletion at 21q22.3 and a breakpoint between D21S53 (present) and D21S212 (absent), centromeric to the known holoprosencephaly (HPE) minimal critical region D21S113-21qter. CONCLUSION: Genetic marker analysis helps in delineating the region of deletion in prenatally detected unbalanced cryptic translocation. Fetuses with concomitant trisomy 18p and distal 21q22.3 deletion may manifest inapparent phenotypic abnormalities in utero. Haploinsufficiency of the HPE critical region at 21q22.3 may not cause an HPE phenotype.     

Prenatal diagnosis and molecular cytogenetic characterization of a de novo interchromosomal insertion of ins(1;8)(p22.1;q22q23)

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a de novo interchromosomal insertion of ins(1; 8)(p22.1; q22q23) at amniocentesis.Case reportA 34-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Conventional cytogenetic analysis revealed a chromosome 1p22.1 interstitial duplication and a chromosome 8q22-q23 interstitial deletion. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis using the DNA extracted from cultured amniocytes revealed no genomic imbalance. Metaphase fluorescence in situ hybridization (FISH) analysis on cultured amniocytes showed an interchromosomal insertion of ins(1; 8)(p22.1; q22q23) or ins(1; 8) (1pter→1p22.1::8q23→8q22::1p22.1→1qter; 8pter→8q22::8q23→8qter). The long arm of chromosome 8 between bands 8q22 and 8q23 had been directly inserted into the short arm of chromosome 1 at band 1p22.1. The karyotype was 46,XY,ins(1; 8)(p22.1; q22q23) or 46,XY,ins(1; 8)(1pter→1p22.1::8q23→8q22::1p22.1→1qter; 8pter→8q22::8q23→8qter). After genetic counseling, the parents decided to continue the pregnancy. A phenotypically normal male baby was delivered at term.ConclusionFISH and aCGH are useful for genetic counseling and molecular cytogenetic characterization of a de novo interchromosomal insertion detected by amniocentesis.     

Prenatal diagnosis of a fetus with terminal deletion of chromosome 1 (q43) in first-trimester screening: is there a characteristic antenatal 1q deletion phenotype? A case report and review of the literature

The terminal deletion of chromosome 1q is a disease of rare incidence. It might be hereditary or caused by spontaneous changes within the chromosome. Phenotypic characteristics including typical facial appearance, microcephaly, psychomotor retardation and variable other anomalies are suggested to be based on the loss of macrochromosomal materials within the long arm of chromosome 1. The number of symptoms is related to the loss of genetic material. To date, only very few cases of terminal 1q deletion syndrome have been diagnosed in utero, mainly after 20 weeks of gestation. Here, we present a case of del(1q)syndrome in a first-trimester fetus. Besides other structural anomalies of the fetus, prenatal ultrasound at 13 weeks' gestation demonstrated severe microgenia and suspicion of cardiac defect. Chorionic villous sampling was performed, and cytogenetic analysis showed a de novo terminal chromosome 1 long arm deletion. We discuss the structural features of antenatally diagnosed fetuses with terminal deletion of chromosome 1 and try to give an answer to the question whether there is a characteristic antenatal 1q deletion phenotype.     

Terminal deletion of chromosome 15q26.1: case report and brief literature review.

Terminal deletions of chromosome 15q are rare events, with only six cases previously described. Here we describe a seventh case of a terminal deletion of the long arm of chromosome 15, with the present case exhibiting clinical features not previously described.     

Prenatal diagnosis and molecular cytogenetic analysis of partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter) in a fetus associated with cystic hygroma and ambiguous genitalia

OBJECTIVES: To present the prenatal diagnosis and molecular cytogenetic analysis of a fetus with nuchal cystic hygroma and ambiguous genitalia. CASE AND METHODS: Amniocentesis was performed at 16 weeks' gestation because of the abnormal fetal sonographic finding of a large septated nuchal cystic hygroma. Genetic amniocentesis revealed a terminal deletion in the long arm of chromosome 10. The paternal karyotype was subsequently found to be 46,XY,t(10;18)(q25.3;q23). The maternal karyotype was normal. The pregnancy was terminated. A hydropic fetus was delivered with a septated nuchal cystic hygroma and ambiguous genitalia. Fluorescence in situ hybridization (FISH), microarray-based comparative genomic hybridization (CGH), and polymorphic DNA markers were used to investigate the involved chromosomal segments. RESULTS: FISH study showed absence of the 10q telomeric probe and presence of the 18q telomeric probe in the derivative chromosome 10. Microarray-based CGH analysis showed loss of distal 10q and gain of distal 18q. Polymorphic DNA marker analysis determined the breakpoints. The fetal karyotype was 46,XY,der(10)t(10;18)(q25.3;q23)pat. The chromosome aberration resulted in partial monosomy 10q (10q25.3-->qter) and partial trisomy 18q (18q23-->qter). CONCLUSIONS: The present case provides evidence that partial monosomy 10q (10q25.3-->qter) with partial trisomy 18q (18q23-->qter) can be a genetic cause of fetal cystic hygroma and ambiguous genitalia. Cytogenetic analysis for prenatally detected structural abnormalities may detect unexpected inherited chromosome aberrations.     

Molecular cytogenetic characterization of a de novo unbalanced translocation leading to trisomy 17q25-->qter and monosomy 18p11.3-->pter in a girl with dysmorphic features

An 18-year-old, gravida 1 underwent percutaneous umbilical blood sampling (PUBS) because of positive triple screen, oligohydramnios and markedly short fetal bones. Chromosome analysis showed an abnormal chromosome 18 with unidentified chromatin at the end of the p-arm. Parental karyotypes were normal. FISH analyses with wcp18 showed additional material of unknown origin on the derivative chromosome 18. Further FISH analysis with subtelomeric probes showed normal signals for the long arm of chromosome 18 (18q23) while no signals were observed for the short arm (18p11.32). These findings were confirmed using a YAC probe from the short arm of 18. The infant was delivered at 30 weeks of gestation. At age 3 months, she was developmentally delayed and has multiple dysmorphic features. Further molecular cytogenetic studies including M-FISH and subtelomere probes showed that the additional material on chromosome 18 consisted of the distal 17q25-->qter region. Based on these studies the karyotype has been interpreted as 46,XX,der(18)t(17;18)(q25;p11.32). To the best of our knowledge, this is the first report of partial monosomy 18p and partial trisomy 17q in a patient with no major CNS malformations. This case shows the importance of molecular cytogenetic techniques in detailed characterization of de novo chromosome rearrangements.