Down syndrome due to partial trisomy 21q

A patient is reported with a typical Down syndrome phenotype, caused by patrial trisomy of chromosome 21. Based on the present case and data from the literature, it is suggested that the Down phenotype is due to the trisomy of the distal portion of the band (q22) of chromosome 21.     

Down syndrome: characterisation of a case with partial trisomy of chromosome 21 owing to a paternal balanced translocation (15;21) (q26;q22.1) by FISH.

A patient with a typical Down syndrome (DS) phenotype and a normal karyotype was studied by FISH. Using painting probes, we found that the patient had partial trisomy of chromosome 21 owing to an unbalanced translocation t(15;21) (q26; q22.1) of paternal origin. To correlate genotype with phenotype as accurately as possible, we localised the breakpoint using a contig of YACs from the long arm of chromosome 21 as probes and performed FISH. We ended up with two YACs, the most telomeric giving signal on the der (15) in addition to signal on the normal chromosome 21 and the most centromeric giving signal only on both normal chromosomes 21. From these results we could conclude that the breakpoint must be located within the region encompassing YACs 280B1 and 814C1, most likely near one end of either YAC or between them, since neither YAC814C1 nor 280B1 crossed the breakpoint (most likely between marker D21S304 and marker D21S302) onband 21q22.1. The same study was performed on the chromosomes of the father and of a sister and a brother of the patient; all three carried a balanced translocation between chromosomes 15 and 21 and had a normal phenotype. We also performed a prenatal study using FISH for the sister. The fetus was also a carrier of the balanced translocation.     

Mental and psychomotoric retardation in two brothers with pure partial trisomy 7q32‐q34 due to a maternal insertion (14;7)

We present two brothers with mental retardation, seizures disorder, generalized muscular hypertonia, kyphoscoliosis, minor anomalies and a prominent midface. GTG‐banded chromosome analysis showed a derivative chromosome 14 without clues toward the origin of the rearrangement. Microdissection of the derivative chromosome 14 and subsequent reverse painting demonstrated partial trisomy 7q32–q34 as the unbalanced product of a maternal insertion (14;7). Thus, we identified two cases with pure trisomy 7q32–q34 that allowed further delineation of this aneusomy syndrome. Am. J. Med. Genet. 91:291–297, 2000. © 2000 Wiley‐Liss, Inc.     

Partial trisomy 6q, due to balanced maternal translocation (6;22) (q21; p13) or (q21; pter)

We report a stillborn infant with partial trisomy 6q who had several major congenital malformations not previously associated with this chromosomal aberration. These included occipital encephalocele, ambiguous genitalia with imperforate anus, omphalocele and unilateral hydronephrosis. The infant's karyotype was 46, XY,-22, der(22), t(6;22)(q21; p13) or (q21;pter)mat. The mother and maternal grandmother are balanced translocation carriers.     

Mental and psychomotoric retardation in two brothers with pure partial trisomy 7q32-q34 due to a maternal insertion (14;7)

We present two brothers with mental retardation, seizures disorder, generalized muscular hypertonia, kyphoscoliosis, minor anomalies and a prominent midface. GTG-banded chromosome analysis showed a derivative chromosome 14 without clues toward the origin of the rearrangement. Microdissection of the derivative chromosome 14 and subsequent reverse painting demonstrated partial trisomy 7q32-q34 as the unbalanced product of a maternal insertion (14;7). Thus, we identified two cases with pure trisomy 7q32-q34 that allowed further delineation of this aneusomy syndrome.     

Hypoplastic left heart in a female infant with partial trisomy 4q due to de novo 4;21 translocation

We present a female infant with mild dysmorphic features and congenital heart defect: hypoplastic left heart with aortic atresia and hypoplastic aortic arch, ventricular septal defect, and a nonrestrictive atrial communication. Chromosome analysis showed an unbalanced translocation that contained additional material from 4q translocated onto 21q. This resulted in partial trisomy 4 and monosomy for the 21q telomeric region. The derivative chromosome was characterized using G-banding, M-FISH, and whole chromosome painting. The karyotype was described as 46,XX,der(21)t(4;21)(q25;q22.3).ish(wcp4+;wcp21+). Additional analyses with FISH probes specific for 21q 22.3, 21q22.2, 21q21.1, and 21q11.2 did not indicate any chromosome 21 duplication within the derivative chromosome 21. Monosomy for the telomeric portion of 21q was demonstrated using a tel 21q probe (Oncor). The patient underwent stage 1 Norwood procedure to manage her heart defect. Poor feeding and failure to thrive complicated the postsurgical period. The child subsequently underwent funduplication and feeding tube placement, and at 4.5 months of age presented with microcephaly and developmental delay. Hypoplastic left heart was previously reported with increased frequency in relatively common numeric chromosomal aberrations, such as monosomy X, trisomies 21, 18, and 13, and in various structural chromosomal defects. Our report presents new evidence for the co-occurrence of hypoplastic left heart with a duplicated portion of chromosome 4 distal to 4q25. In addition, monosomy for the telomeric region of chromosome 21 may have implications in the phenotype.     

Familial t (4;21)(q2.4;q2.2) leading to unbalanced offspring with partial duplication of 4q and of 21q without manifestations of the Down syndrome

We report on an infant with a malformation syndrome who had a combination of partial duplication of 4q and 21q as the result of a maternal unbalanced translocation. She has duplication of the proximal portion of chromosome 21, without manifestation of the Down syndrome.     

Partial trisomy 20 (20q13) and partial trisomy 21 (21pter leads to 21q21.3).

A patient with a double partial trisomy 20 and 21 with mild mental retardation and multiple congenital anomalies is presented. Despite trisomy for a substantial portion of chromosome 21, the patient showed only minor stigmata compatible with Down syndrome.     

Subtle translocation (18;21) confirmed by FISH in a patient with Down syndrome

The patient presented with the typical features of Down syndrome: hypotonia, brachycephaly, flattened occiput, bilateral prominent medical epican-thic folds, flat nasal bridge, protruding tongue, low-set dysplastic ears, short broad hands, bilateral clinodactyly and simian crease. The karyotype of this child was originally reported as normal. High-resolution chromosomes revealed extra material on the long arm of chromosome 18. The mother's karyotype showed a reciprocal translocation between the long arm of 18 and the long arm of 21 at band q23 and q22.1, respectively. FISH performed separately with two different 21q cosmid probes gave two signals on the mother's metaphases and three signals on the prob-and. These findings confirmed that the proband is trisomic for the long arm of chromosome 21 at loci D21S65 and D21S19.     

Duplication 8q syndrome due to familial chromosome ins(10;8)(q21;q212q22)

We describe a kindred in which an ins(10;8)(q21;q212q22) chromosome rearrangement has been segregating for at least four generations. The risk for balanced carriers to have offspring with duplication of 8q212→8q22 is about 0.31. Individuals with unbalanced chromosomes are mildly to moderately mentally retarded and have a similar unusual appearance. Other manifestations include highly arched or cleft palate (8/9), micrognathia (6/9), sloped shoulders (4–6/9), convulsions (4/9), camptodactyly (3/9), pectus excavatum (2/9), elbow contractures (1/9), and postaxial polydactyly (1/9). The appearance and habitus resemble the mosaic trisomy 8 syndrome, although other anomalies of mosaic trisomy 8, such as vertebral, patellar, and renal defects, were not demonstrated.     

Partial trisomy 18 in a family with a translocation (18;21)(q21;q22).

A family is described in which 2 sibs had similar congenital abnormalities. Chromosome investigation of the mother and another child disclosed they were carriers of a translocation t(18;21)(q21;q22). The karyotype of one of the abnormal infants was determined and was found to be consistent with partial trisomy 18,46,XY,-21,+der (21),t(18;21) ((18pter leads to 18q21::21q22 leads to 2 lqter)mat.     

Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion 5(p15.1q35.1)

A male infant with karyotype 46,XY,rec(5),dup q,inv(5)(p15.1 q35.1)pat is presented. The proband showed growth and developmental retardation, complex cardiovascular abnormalities, inguinal hernia and microcephaly in addition to facial appearance and cat-like cry characteristic of the cri-du-chat syndrome. Growth and developmental retardation, and microcephaly noted in this patient were markedly more serious than those observed in patients either with partial monosomy 5p or with partial trisomy 5q alone.     

Familial partial monosomy 5p and trisomy 5q; three cases due to paternal pericentric inversion 5 (p151q333)

A family is described in which the mother's 9 pregnancies ended in the birth of 2 healthy girls, 4 spontaneous abortions and 3 infants with multiple congenital malformations as bird-headed appearance, pre- and postnatal growth deficiency, microcephaly, micrognathia with small mouth and cat-like cry. Two of the three affected sibs had complex cardiac malformations incompatible with life; the third had a bicuspid aortic valve. Chromosomal investigation revealed an abnormal karyotype: 46,XX,rec(5),dupq,inv(5)(p151q333)pat, leading to a partial monosomy 5p and partial trisomy 5q. A large pericentric inversion of chromosome 5 was found in the father: 46,XY,inv(5)(p151q333) as well as in the firstborn healthy female sib. The clinical features partly fit the partial monosomy 5p as well as the partial trisomy 5q syndrome.     

Partial trisomy 3q due to a de novo translocation t(X;3) (p21;q12)

A patient with several congenital malformations, principally in the face, cardiovascular system and genitalia, was found to have the karyotype 46 ,X,der(X),t,X;3)(Xqter← p21::3ql2-←3qter). A comparison of the clinical and cytogenetical findings with similar cases in the literature led to the conclusion that a partial trisomy 3q is the most likely cause for the symptoms in this patient.     

Prenatal diagnosis of partial trisomy 21 associated with maternal balanced translocation 46xx der 21 t(21q;22q) with pericentric inversion of chromosome 9

This communication reports prenatal diagnosis of partial trisomy 21 resulting from balanced translocation (21q;22q) in a 36-year-old gravida 7, para 1 woman. The lady had only one living child and there was history of recurrent spontaneous first trimester abortions. Triple test was abnormal in the present conception. In addition, the woman had pericentric inversion of chromosome 9, a finding scarcely reported previously with carrier status in Indian literature. A few cytogeneticists consider this as a normal variant. However, many reports in the recent literature link pericentric inversion of chromosome 9 with infertility, recurrent abortions and a number of other abnormal conditions. A review of the relevant literature pertinent to the case is provided.     

一例1q部分三体4q部分单体导致Pierre Robin序列征的遗传学分析

目的:对1例临床诊断为Pierre Robin序列征的患儿进行细胞及分子遗传学分析,寻找遗传学病因。方法:应用外周血染色体核型分析、核苷酸多态性微阵列检测和荧光原位杂交技术,分别对1例表型为下颌小、舌后坠、上呼吸道阻塞、上颚裂开、颈短的患儿及其正常表型的父母进行检测。结果:患儿核型为46,XY,der(4)add(4)...     

Interrupted aortic arch in a child with trisomy 5q31.1q35.1 due to a maternal (20;5) balanced insertion

Complex congenital heart defects (CHD) are associated with a variety of single gene abnormalities and chromosomal rearrangements. Of the various forms of CHD, aortic arch interruption, a conotruncal heart defect, is relatively uncommon. Here we report a male neonate with aortic arch interruption type B, secundum atrial septal defect, perimembranous ventricular septal defect, patent ductus arteriosus, aortic and subaortic stenosis, and trisomy 5q31.1q35.1 resulting from a maternal balanced insertion (20;5). Chromosomal deletions, including deletion 22q11, have been reported with interrupted aortic arch (IAA); however, to our knowledge this is the first report of a trisomy of distal chromosome 5q associated with aortic arch interruption. Here we compare this child's features to other cases of trisomy 5q31.1q35.1, and review other causes of IAA. We conclude that gene dosage in this chromosomal region likely influences aortic arch development.