Partial 3p trisomy and different rearrangements involving chromosome 3 in the proposita's family

A case of partial 3p trisomy is reported here. A review of published cases (8 ♂, 2 ♀, 7 families) shows a characteristic pattern of anomalies, constituting one more syndrome of multiple congenital anomaly and mental retardation (MCA/MR) characterized by microcephaly, brachycephaly, frontal bossing, temporal indentation, square face, hypertelorism or telecanthus, epicanthus, short nose with a large tip, prominent cheeks, long and protruding philtrum, large and downturned mouth, protruding mid-upper lip, micro- or retrognathia, short neck, congenital heart defects, gastrointestinal malformation, penile hypoplasia, neuromotor or mental retardation, and predominance of whorls on digits. The proposita had a 46,XX,der(11),t(3;11)(p21;q25) karyotype. The mother was a carrier of a de novo 3;11 balanced translocation. Chromosome mosaicism was detected in a female sibling of the proposita: 46% of her cells were 46,XX and 54% had a 46,XX,t(3;20)(p21;q13) karyotype - ie, a de novo 3;20 balanced translocation. We discuss the origin of this mosaicism and the possible meaning of the breaks involving the same region of chromosome 3 (region 3p21) in the members of the proposita's family.     

Clinical delineation of proximal and distal partial 13q trisomy

The most relevant phenotypic features seen in both proximal and distal partial trisomy 13 have been identified from a review of 35 cases. Clinical delineation of either proximal or distal partial trisomy 13 has been demonstrated through the use of conspicuous phenotypic differences. The findings of persistent foetal Hb and increased number of nuclear projections on neutrophils are consistent findings associated with partial trisomy of a proximal segment of chromosome 13 and are diagnostic for trisomy of a partial segment of chromosome 13 that contains bands 13q12 and 13q14. The physical features of polydactyly and hemangioma have been mapped to bands 13q31 and 13q32----13qter and provide a differential diagnosis for a distal trisomic segment of chromosome 13 that may include bands 13q22----13qter. A segment of chromosome 13 has been identified that does not produce any detectable phenotypes in the triplicated state. The possible role of a triplicated 13q segment in altering expression of structural and regulatory systems elsewhere in the genome has been examined. Distinct clinical syndromes involving either a partial proximal or partial distal trisomic segment of chromosome 13 may be phenotypically defined.     

Duplication 3p syndrome: Report of a new case and review of the literature

A review of the 17 previously reported cases of duplication 3p and study of a new patient who has a duplication of the chromosome segment 3p21→pter show a remarkably consistent phenotype among these patients and suggest some generalizations about prognosis. The manifestations include low birth weight, short stature, microcephaly, characteristic “square” face with temporal indentations, hypertelorism and/or telecanthus, epicanthus with a broad nasal bridge and large nasal tip, and down-turned corners of the mouth. Cleft lip/palate and eversion of the lips are common. The jaw is typically small and receding and the neck short. Congenital heart disease, gastrointestinal malformations, abnormalities on intravenous urography, and defective masculinization of the male infants are frequently observed. A predominance of whorls is present on the fingers. Nearly half of the cases died before 6 months. All affected children surviving beyond 1 year have been mentally retarded.     

Delineatino of the da-Silva syndrome

We present a 6-month-old boy with agenesis of the corpus callosum, hypertonicity, severe growth and psychomotor retardation, microcephaly, large prominent ears, and delayed bone age. Similarity of his manifestations to these in 3 sibs described by da-Silva in 1988 suggests initial delineation of the da-Silva syndrome. © 1994 Wiley-Liss, Inc.     

FG syndrome: Report of three new families with linkage to xq12-q22.1

FG syndrome is a rare X-linked recessive form of mental retardation, first described by Opitz and Kaveggia in 1974 in five related males with mental retardation, disproportionately large heads, imperforate anus, and congenital hypotonia. Partial agenesis of the corpus callosum was noted in at least one of the initial cases and has been seen in a number of subsequently-reported cases. The associated congenital hypotonia with joint hyperlaxity tends to progress to contractures with spasticity and unsteady gait in later life. The presence of subtle facial abnormalities and the characteristic behavior in midchildhood facilitate diagnosis at this age, particularly when there are other affected male relatives in the maternal family. Recently, Briault et al. [1997[ mapped a gene for FG syndrome to the Xq12-q21.31 region. We describe three additional families (six additional patients) with FG syndrome on whom we have conducted linkage analysis. Our findings support the localization of a gene for the FG syndrome in Xq12-q21. In addition, we have noted skewed X-inactivation in carrier females, as well as new associated findings in affected males of sagittal craniosynostosis and split hand malformation. Am. J. Med. Genet. 80:145–156, 1998. © 1998 Wiley-Liss, Inc.     

The trisomy 4p syndrome: Case report and review

We report a further case of trisomy 4p: a 5-year-old mentally retarded boy with characteristic facial features, eye abnormalities, flexion contractures, several bone anomalies, and hyperactivity. In a review of 27 cases (11♂, 16♀, 22 families) the cytogenetic and clinical data were tabulated and analyzed. Diagnosis is established by karyotype: there is always partial or apparently “total” trisomy of the short arm of chromosome 4. In 19 families a parent carried either a balanced translocation (16 times) or a pericentric inversion (3 times); 3 patients had de novo duplication of 4p. In several cases, additional deletions or trisomies were present. From the analysis of all cases, but particularly of the “pure” trisomies, the phenotypic spectrum of this condition was observed and found to be a specific multiple congenital anomaly/mental retardation (MCA/MR) syndrome. Its main features are a characteristic facial appearance, postnatal growth retardation, severe psychomotor retardation with or without seizures, microcephaly, and various major and minor anomalies.     

两例分别由父源性平衡易位和母源性插入易位导致8p部分三体智力低下患儿的临床表型和遗传学分析

目的 明确两例智力低下患儿8号染色体短臂异常性质和来源,分析其染色体改变与表型的相关性.方法 首先应用常规G显带分析2例患儿及父母外周血染色体改变,然后应用比较基因组杂交芯片(array comparative genomic hybridization,array CGH)对其中1例常规核型分析的结果进行精确定位.结果 例1母亲的染色体改变为8p和3q的平衡插入易位,该患儿继承了母亲的1条衍生3号染色体,核型为46,XX,der(3) inv ins (3;8)(q25.3;p23.1p11.2)mat,导致8p部分三体.Array CGH分析显示重复区域为8p11.21-8p22,片段大小为26.9 Mb,该患儿主要表现为智力低下,未见其他8p三体的典型临床特征.例2父亲的核型为8p和11q的平衡易位,该患儿继承了父亲的1条衍生11号染色体,核型为46,XX,der(11)t(8;11)(p11.2;q25)pat,临床表现为智力低下,特殊面容,同时伴有先天性心脏病和骨骼异常,与典型8p三体表型相似,但面容特征不典型.结论 8p部分三体是2例患儿异常表型的主要原因,但与典型的8p三体相比,表型存在异质性;父母染色体分析可以帮助明确易位的性质从而有利于再发风险评估;与传统的细胞遗传学分析方法相比,arrayCGH在染色体异常分析中具有更高的分辨率和准确性.

Abstract：

Objective To determine the origin of aberrant chromosomes involving the short arm of chromosome 8 in two mentally retarded children, and to correlate the karyotype with abnormal phenotype. Methods Routine G-banding was performed to analyze the karyotypes of the two patients and their parents, and array comparative genomic hybridization (array CGH) was used for the first patient for fine mapping of the aberrant region. Results The first patient presented with only mental retardation. The father had normal karyotype. The mother had an apparent insertion translocation involving chromosomes 8 and 3 [46,XX, inv ins (3;8) (q25.3;p23.1p11.2)], the karyotype of the child was ascertained as 46,XX,der(3) inv ins (3;8)(q25.3;p23.1p11.2). Array CGH finely mapped the duplication to 8p11.21-8p22, a 26.9Mb region. The other patient presented with mental retardation, craniofacial defects, congenital heart disease and minor skeletal abnormality. The mother had normal karyotype. The father had an apparently balanced translocation involving chromosome 8p and 11q, the karyotype was 46,XY, t(8;11)(p11.2;q25). The karyotype of the child was then ascertained as 46,XX,der(11)t(8;11)(p11.2;q25). Conclusion These results suggested that partial trisomy 8p was primary cause for the phenotypic abnormalities of the two patients, whereas a mild phenotypic effect was observed in patient 1. Parental karyotype analysis could help define the aberrant type and recurrent risk evaluation. In contract to routine karyotype analysis, aberrant regions could be mapped by array CGH with higher resolution and accuracy.     

Variable phenotype associated with duplication of different regions of 2p

Previous reports suggest that duplication of the distal part of 2p causes a distinct syndrome. Of the 20 published cases, all resulted from a parental translocation. We report here clinical and cytogenetic data on three patients with dup(2p) and few, if any, of the physical findings of the syndrome. Our data suggest that dup(2p) is associated with an extremely variable phenotype which may be quite mild in some cases. It is also possible that many of the nonspecific developmental anomalies thought to be part of the syndrome may be caused by the accompanying deletion.     

Mosaic trisomy 22: A case presentation and literature review of trisomy 22 phenotypes

In a case of mosaic trisomy 22 the trisomic cells were detected primarily in fibroblasts. Results of initial lymphocyte chromosome analysis were normal. However, mosaicism was suspected because the patient had hypomelanosis of Ito, hemiatrophy, failure to thrive, and mental retardation. Mosaicism was confirmed in cultured fibroblasts. Repeat cytogenetic analysis of peripheral blood demonstrated a low level of trisomic metaphase cells, which was confirmed by interphase fluorescent in situ hybridization (FISH) analysis. Molecular studies supported maternal disomy in the child's disomic cells. The phenotype of this condition overlaps that of non-mosaic trisomy 22 chromosome mosaicism in general and to some extent the Ullrich-Turner syndrome phenotype. Improved cytogenetic and molecular techniques now allow better delineation of aneuploidy syndromes. Molecular and FISH studies added information about this case (mosaicism and uniparental disomy) not appreciated by routine cytogenetic analysis of lymphocytes. The detection of low-level mosaicism and/or uniparental disomy in such cases may change the clinical classification and our understanding of pathogenesis and recurrence risk of these disorders. Am. J. Med. Genet. 71:406–413, 1997. © 1997 Wiley-Liss, Inc.     

“C” Trigonocephaly syndrome: Report of a child with agenesis of the corpus callosum and tetralogy of Fallot,and review

We report on a new case of the Opitz “C” trigonocephaly syndrome. Our patient had agenesis of the corpus callosum, an anomaly seen only twice previously, and tetralogy of Fallot, described only once before. A review shows that a combination of conotruncal heart defects and midline brain anomalies characterizes patients with this entity. © 1995 Wiley-Liss, Inc.     

Trisomy 14 mosaicism: Case report and review

Complete or partial trisomy 14 is compatible with life. However, in the former case, mosaicism is probably always present. A case of trisomy 14 mosaicism is reported. Comparisons are made with other trisomy 14, trisomy 14 mosaicism, and duplication 14q cases previously reported. As a group, they share some clinical manifestations. The phenotype consists of multiple congenital anomalies, including microcephaly, broad nose, wide mouth, high or cleft palate, micrognathia, congenital heart disease, intrauterine growth retardation, and mental retardation. The present patient also has asthma, eczema, and developmental asymmetry.     

Partial trisomy 10 mosaicism with cutaneous manifestations: report of a case and review of the literature

A female infant with partial trisomy 10 mosaicism and hypomelanosis of Ito is presented. Features include a prominent forehead, hypertelorism, large dysplastic ears, prominent nasal root, a cleft lip and alveolar ridge, bilateral metatarsus adductus, and streaks and whorls of hypopigmented skin. The skin findings were diagnostic for hypomelanosis of Ito. A peripheral blood karyotype was normal. Fibroblasts from a junctional skin biopsy revealed mosaicism for partial trisomy of chromosome 10 [46, XX/47, XX, +del(10) (q11.2q23.2)]. The physical findings of this patient are compared to five published cases of complete trisomy 10 mosaicism and 94 cases of isolated trisomy 10p and trisomy 10q.     

Infant with del(3) (p25-pter): Karyotype-phenotype correlation and review of previously reported cases

We describe a boy with monosomy for the distal part of the short arm of chromosome 3. He had a congenital heart defect, tetramelic hexadactyly, and typical craniofacial anomalies. Comparison with previously reported cases confirms that the phenotype consists of an identifiable pattern of malformation.     

Identification and characterization of a de novo partial trisomy 10p by comparative genomic hybridization (CGH)

We report the characterization of a de novo unbalanced chromosome rearrangement by comparative genomic hybridization (CGH) in a 15-day-old child with hypotonia and dysmorphia. We describe the combined use of CGH and fluorescence in situ hybridization (FISH) to identify the origin of the additional chromosomal material on the short arm of chromosome 6. Investigation with FISH revealed that the excess material was not derived from chromosome 6. Identification of unknown unbalanced aberrations that could not be identified by traditional cytogenetics procedures is possible by CGH analysis. Visual analysis of digital images from CGH-metaphase spreads revealed a predominantly green signal on the telomeric region of chromosome 10p. After quantitative digital ratio imaging of 10 CGH-metaphase spreads, a region of gain was found in the chromosome band 10p14-pter. The CGH finding was confirmed by FISH analysis, using a whole chromosome 10 paint probe. These results show the usefulness of CGH for a rapid characterization of de novo unbalanced translocation, unidentifiable by karyotype alone.     

Partial agenesis of the corpus callosum, hippocampal atrophy, and stable intellectual disability associated with Roifman syndrome

In 2006, we reported the cognitive and behavioral phenotype of the seventh case of Roifman syndrome (OMIM 300258). Aged 11 years 6 months, the patient displayed significant intellectual disability with proportionate impairments in attentional-executive, memory, and visuo-spatial abilities despite appearing socially "able." This discrepancy may be explained by good social-emotional skills masking his intellectual disability, by decline in cognitive abilities over time, or by unusual neuroradiological abnormalities not previously examined in Roifman syndrome. Here, we present results from a structural MRI scan, neurocognitive evaluations repeated 2 and 5 years post-baseline and assessments of face and emotional processing. The MRI revealed partial agenesis of the corpus callosum, bilateral hypoplastic hippocampi but bilaterally intact amygdala. No evidence was found for decline in the patient's neurocognitive profile. Emotional processing data indicated an age-appropriate pattern of reactivity to emotional stimuli and preserved facial identity recognition abilities, but impairments in recognition of negative facial expressions. The results confirmed a stable pattern of intellectual disability, and indicated that Roifman syndrome may be associated with major structural neuro-anatomical abnormalities. We suggest that the relative strengths in emotion and face processing are consistent with the patient's apparently able social behavior, and with intact amygdalar function.