The 11q- Syndrome with Mosaic Partial Deletion of 11q

A female child with mosaic partial deletion of 1 lq is reported. At 1 month of age she was presented with congenital glaucoma, trigonocephaly and multiple minor anomalies. She exhibited growth retardation and the typical phenotype of llq- syndrome. G-banding analysis failed to show any abnormality, although subsequent high resolution banding revealed the abnormal karyotype mos 46,XX,del(11)(q23.3 q24.2)/46,XX,del(11)(q23.3 q25). This case is a second case of mosaic llq- syndrome and her karyotype suggests that the region of 11q23.3–11q24.2 is critical in 11q- syndrome. Congenital glaucoma has never been reported as a complication of llq- syndrome.     

5q- syndrome in a child with slowly progressive pancytopenia: a case report and review of the literature

5q- syndrome is a rare myelodysplastic process occurring predominately in middle aged to elderly women. In children, myelodysplasia of all types is rare and 5q- syndrome is exceptionally rare. Only 6 cases of 5q- associated myelodysplasia have been reported in children and all 6 cases had blast counts >5% and/or additional cytogenetic abnormalities. We report a case of 5q- syndrome in a girl who presented with macrocytosis and intermittent pancytopenia at age 5. Cytogenetic studies at age 8 revealed a large interstitial deletion of chromosome 5q without other cytogenetic abnormalities. The patient was clinically stable until age 11, when she became transfusion dependent and severely neutropenic. Subsequently, she underwent a successful unrelated cord blood transplant. To our knowledge, this is the first reported pediatric case meeting the strict criteria for 5q- syndrome.     

Myelodysplastic Syndrome with Partial Deletion of the Long Arm of Chromosome 5: First Report of a Case in a Child

A childhood case of myelodysplastic syndrome (MDS) with a deletion of the long arm of chromosome 5 (5q-) is reported. The patient was an 8 year old boy who has recurrent angina. Laboratory evaluation revealed the following: hemoglobin 8.1 gm/dl, white blood cell count 4.9 × 10³/l with 3% atypical lymphocytes, and platelet count 17.7 × 10⁴/l. A bone marrow aspirate revealed 20% blast cells and dysmyelopoietic changes involving all three marrow cell lines. Karyotype analysis of marrow cells revealed 46,XY,5q- in 100% of the metaphases.
These findings led to a diagnosis of MDS with 5q-, which is most commonly found in adult MDS. This case seems to represent an exceedingly rare childhood case of MDS with 5q-.     

Occurrence of high‐grade glioma in Noonan syndrome: Report of two cases

Noonan syndrome (NS) is an autosomal dominant disorder commonly caused by PTPN11 germline mutations. Patients are characterized by short stature, congenital heart defects, facial dysmorphism, and increased risk of malignancies including brain tumors. Commonly associated brain tumors are dysembryoplastic neuroepithelial tumor and low‐grade glioma. We report two cases of anaplastic astrocytoma with PTPN11‐related NS. We conducted a systematic search of medical databases looking for other reported cases of high‐grade glioma associated with NS and identified 24 cases of brain tumors, all of which were low‐grade glial or glioneuronal tumors except for one case of medulloblastoma.     

18q- syndrome in mother and daughter

The 18q- syndrome is described in a mother and her daughter. In both of them an identical, apparently balanced 18q-/14p+ translocation was found (Karyotype: 46,XX,t(14;18)(p11;q21)), suggesting that chromosomal material was lost in the process of translocation. The segment deleted and responsible for the 18q- phenotype must be located in or near band 18q21, in which the break is assumed to have occurred.     

Comprehensive genetic analysis of overlapping syndromes of RAS/RAF/MEK/ERK pathway

Background: Germline mutations in several members of RAS/RAF/MEK/ERK pathway cause clinically similar genetic disorders, including Noonan syndrome (NS), Costello syndrome (CS) and cardio‐facio‐cutaneous syndrome (CFC). Each of these syndromes has a wide spectrum of molecular etiology. The aim of the present study was to conduct a comprehensive genetic analysis of RAS/RAF/MEK/ERK pathway in these syndromes. Methods: Three patients with NS and two patients with CS/CFC were examined. Peripheral blood samples were collected from all patients as well as from 100 healthy Japanese volunteers. The protein phosphatase, non‐receptor type II (PTPN11), KRAS, HRAS, NRAS, BRAF, RAF1, Son of Sevenless (SOS1) and MEK1genes were analyzed. Results: In a patient with a severe Noonan phenotype, a rare PTPN11 mutation was detected: A to G transition at position 172, causing an N58D substitution within the N‐SH2 domain. In a CS/CFC patient no HRAS mutations were found, but a novel SOS1 missense mutation was found: A to G transition at position 473, causing a T158A substitution within domain of histone‐like fold (HF). Conclusions: A case mimicking CS with SOS1 T158A substitution, which has not been reported previously in CS, revealed the complex relationship between the genotype and phenotype of overlapping syndromes of the RAS/RAF/MEK/ERK pathway.     

A 13q- syndrome with extensive intestinal atresia

The first autopsy case of a 13q- syndrome with extensive intestinal atresia, viz., absence of almost the entire jejunum and ileum, is reported. The absence of the mesentery and the histological properties of the intraperitoneal string-structures composed of some muscle layers resembling the tunica muscularis of the alimentary tract suggest that one of the causative agents of the atresia may be abnormalities of mesenteric vessels.     

A 13q- Syndrome with Extensive Intestinal Atresia

ABSTRACT. The first autopsy case of a 13q- syndrome with extensive intestinal atresia, viz., absence of almost the entire jejunum and ileum, is reported. The absence of the mesentery and the histological properties of the intraperitoneal string-structures composed of some muscle layers resembling the tunica muscularis of the alimentary tract suggest that one of the causative agents of the atresia may be abnormalities of mesenteric vessels.     

The clinical and genetic picture of trisomy 18 (Edwards' syndrome)

Six patients with Edwards' syndrome were studied. One child (case 2) was found to have a structural anomaly of a B chromosome as well as an extra chromosome of pair No. 18: 47,XY,18+,inv.(Bp+q-). Case 3 showed additional malformations not commonly present in Edward's syndrome. Case 4 was a twin; the twin sister was clinically and chromosomally normal. In case 6, which came to our attention after the discovery of the banding technique, it was possible to diagnose as trisomy 18 unequivocally by this method. Some striking features of the dermatoglyphics and creases are discussed.

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Zusammenfassung Es wurde über 6 Patienten mit Edwards-Syndrom berichtet. Ein Kind (Fall 2) zeigte außer Extrachromosom Nr. 18 eine strukturelle Anomalie eines B-Chromosoms: 47,XY,18+,inv.(Bp+q-). Bei Fall 3 waren einige beim Edwards-Syndrom unübliche Mißbildungen vorhanden. Bei dem 4. Kind handelte es sich um eine Zwillingsgeburt, die Zwillingsschwester war klinisch und chromosomal normal. Ein Fall von Trisomie 18, der uns nach der Entdeckung der Bandentechnik bekannt wurde, konnte, mit dieser Technik einwandfrei als Trisomie 18 diagnostiziert werden. Einige Auffälligkeiten im Bereich der Dermatoglyphen wurden demonstriert.

     

Pilocytic astrocytoma in a child with Noonan syndrome

Noonan syndrome (NS; MIM 163950) is an autosomal dominant dysmorphic syndrome characterized by distinct facial features, cardiac anomalies, short stature, and motor delay. Activating mutations in PTPN11, encoding the protein tyrosine phosphatase SHP2, are associated with about 50% of cases. Mutations in other genes in the RAS/mitogen‐activated protein kinase signaling pathway are responsible for many of the remainder of cases. While mutations in this pathway are found in a variety of malignancies, including solid tumors, there are few reports of solid tumors in individuals with NS. We report here a patient with PTPN11 mutation‐associated NS and a pilocytic astrocytoma. Pediatr Blood Cancer 2009;53:1147–1149. © 2009 Wiley‐Liss, Inc.     

多重连接探针扩增技术在先天性心脏病22q11微缺失/微重复综合征诊断中的应用

目的染色体22q11区域基因拷贝数异常是先天性心脏病(CHD)的遗传病因之一,由其引起的CHD预后不良。该研究主要探讨多重连接探针扩增技术用于CHD22q11微缺失或微重复遗传病因诊断的实用性,并了解22q11微缺失或微重复在CHD中的发生情况。方法选择25个位于染色体22q11低重复拷贝序列A-H区域内、7个位于其周围(CES、22q13)和16个位于4、8、10、17号染色体上的基因位点共计48个探针组成多重连接探针,对181例外科手术前的CHD儿童和14例严重CHD或包括CHD的多发性畸形胎儿进行了22q11微缺失或微重复的检测,并进行了染色体核型分析。结果195例患儿中,共检出22q11微缺失者7例(LCRA-D区6例,LCRA-C区1例),22q11微重复1例(LCRB-D区),涉及的CHD类型包括室间隔缺损、房室间隔缺损、肺动脉狭窄和法洛四联征。同时染色体核型分析还发现了6例异常:1例21q部分缺失[46,XY,21q-],1例嵌合性8-三体[47,XY,+8/46,XY(1∶2)],4例21-三体。其中1例21-三体与22q11微重复同时存在。结论染色体22q11区域高密度多重连接探针检测技术能快速、灵敏、精确定位诊断染色体22q11区域基因拷贝数异常,适合于CHD的遗传学诊断;此外,22q11微缺失或微重复引起的CHD类型多种多样,建议所有CHD患者应常规进行遗传学检测。     

Sporadic bilateral retinoblastoma and 13q-chromosomal deletion

Unilateral retinoblastoma (Rb) is usually a sporadic occurrence while bilateral (multi-focal) cases are often familial. Sporadic bilateral Rb associated with a long-arm deletion of a D-group chromosome has been reported in 8 children. We have studied a 6-year-old female with bilateral sporadic retinoblastoma, treated during infancy by enucleation and radiotherapy. Chromosome banding studies on peripheral lymphocytes revealed an interstitial deletion from the long arm of a chromosome 13: del(13) (q12q14). Three additional patients reported in the literature had interstitial 13q- deletions, involving slightly different though overlapping regions. The only chromosomal region consistently missing in all of these 4 cases appears to be part of the lightly staining band 13q14. We, therefore, propose this site as the precise location of a gene (or genes) involved in retinal development. Our patient lacked features of the classic 13q- or 13-ring syndrome, which involves deletion of a more distal portion of the 13 long arm. When compared to reported patients with Rb and 13q-, it became apparent that there may be a separate recognizable syndrome consisting of moderate growth and developmental delay, characteristic facies and external ears, and bilateral sporadic Rb, which is associated with an interstitial 13q- deletion.     

Translocation t(8;14)(q24;q11) with concurrent PTEN alterations and deletions of STIL/TAL1 and CDKN2A/B in a pediatric case of acute T‐lymphoblastic leukemia: A genetic profile associated with adverse prognosis

We report a pediatric case of acute T‐lymphoblastic leukemia (T‐ALL) with NOTCH1^wt, FBXW7^wt, STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)‐positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations. This case documents an unfavorable prognostic potential of a co‐occurrence of this set of molecular genetic events and addresses risk stratification in T‐ALL.     

Chromosomal Analysis of Childhood Acute Lymphoblastic Leukemia: As a Routine Examination for Diagnosis and Prognosis

Chromosomal analysis was performed as a routine examination for diagnostic and prognostic evaluation of children with acute lymphoblastic leukemia (ALL) in six cases encountered during a one-year period. The results obtained are as follows. 1. Chromosomal abnormality of leukemic cells was observed in five out of six cases (approximately 80%). 2. Translocation 4; 11 or 14q+, which are known as a risk factor of ALL, were observed in three patients. Two of three patients died within six months of the onset of disease. One case was diagnosed as congenital leukemia with remarkable leukocytosis, and the other case was accompanied by hypereosinophilic syndrome. The remaining one patient, who is now in complete remission, is 13 years old, which is within the period of risk ages exceeding 10 years of age. 3. The case with 1q+ had no risk factor; however, he had a relapse 19 months after the diagnosis. Thus this particular chromosomal rearrangement appeared to be one of the risk factors. 4. The case with 6q-, which has been reported to have a good prognosis in some cases of ALL, has no risk factor, and has been in complete remission. These results seem to confirm the usefulness of chromosomal analysis for the evaluation of the clinical course of ALL.     

Partial deletion of the long arm chromosome II in Jacobsen syndrome

The Jacobsen syndrome (11q23←11gter) consists of trigonocephaly, facial dysmorphism, mental retardation, and hypotonia. Seventeen patients with this syndrome have been reported in literature—fourteen female and three male. This report is the eighteenth case with deletion 11q23→11qter in a 11/2 year old male. Such a case has not been reported from India. A review of the reported cases with comparisons of their features has been made.     

11q24-q25缺失2例临床表型及文献复习

目的 应用全基因组微阵列芯片平台,对临床发现的多发性畸形患儿进行全基因组拷贝数变异（CNVs）的检测,并寻找基因型与临床表型的关系。方法 采用cytogenetic whole genome芯片筛查全基因组CNVs,针对发现的CNVs进行分析,参照国际基因组CNVs多态性数据库除外正常人群多态性CNVs。结合本研究2例与已报道的Jacobsen综合征(JBS)患儿的临床表型进行比较。结果 2例患儿SNP芯片分析为11q24-q25缺失（7.5和5.6 Mb）,均为末端的非单纯性缺失,例1存在12号染色体短臂的较大片段重复（11.5 Mb）,例2存在 11号染色体短臂的大片段重复（32.5 Mb）。2例共同缺失的部分均为JBS的关键区段,但临床表型与已报道的JBS患儿有所区别。2例均表现为头面部畸形、心血管系统异常和头颅影像学异常,均未发现血液系统异常。例1还表现为隐睾,例2表现为脾肿大。结论 对临床上难以诊断的多发性畸形可采用全基因组CNVs检测,以帮助明确诊断,对于丰富这一区段临床表型信息具有重要意义,尤其针对罕见疾病,更多的相似报道的后续出现,才能使建立表型-基因型关联性成为可能。     

Trisomy 21 q: 46,XX,21s+/47,XX,+21q−(q22→qter) mosaicism (de novo) in a down syndrome child

A three year old girl with clinical features of Down syndrome and mental retardation is reported. Karyotype of the proband was 46,XX,21s⁺/47,XX,21q→(q22−qter), resulting in partial trisomy for chromosome 21. Her father, phenotypically normal, was a carrier for 21s+variant chromosome (46,XX,21s⁺). The maternal age was 32 years. This case further confirms that the Down phenotype is due to the trisomy of the distal segment of the band q22 of chromosome 21.     

4q- syndrome.

To our knowledge, there have been three prior reports of patients found, with trypsin-Giemsa banding, to be monosomic for the terminal q segment of chromosome 4. Described herein is a fourth patient with this chromosome abnormality. Comparison of these four patients suggests a characteristic phenotype in the 4q- syndrome: cleft palate, satyr deformity of the pinnae, snub nose, retrognathia and micrognathia, hypertelorism, oropharyngeal hypothonia or upper airway obstruction, cardiac defect, clinodactyly of the fifth fingers with absence of a flexion crease, simian lines, displaced or clinodactylous toes, and mental retardation. In the three prior reports, the 4q- syndrome resulted from a de novo deletion. In the present case, the 4q monosomy was inherited from the father, who had a 4;20 translocation.     

Efficacy of levamisole in children with frequently relapsing and steroid-dependent nephrotic syndrome

Objectives

To assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome.

Study Design

Retrospective analysis of hospital case records.

Setting

Pediatric nephrology department of a tertiary referral pediatric hospital.

Participants

62 children with frequently relapsing nephrotic syndrome and 35 children with steroid-dependent nephrotic syndrome.

Methods

Case records of children who were diagnosed as steroid-dependant or frequently-relapsing nephrotic syndrome from June 2004 to June 2011, were reviewed. Levamisole was given daily (2 mg/kg/d) along with tapering doses of alternate day steroids after remission on daily steroids.

Results

Levamisole was effective in 77.3% children with a better (80.6%) efficacy in frequently relapsing nephrotic syndrome. A total of 34 children completed 1 year follow-up post levamisole therapy. The cumulative mean (SD) steroid dose 1-year before therapy was 4109(1154) mg/m² and 1-year post therapy was 661 (11) mg/m² (P<0.001). The relapses were also less during the period of post-levamisole therapy.

Conclusion

Levamisole is an effective alternative therapy in frequently relapsing and steroid-dependent nephrotic syndrome.     

A case of siblings with Meckel's diverticulum diagnosed before operation

The authors encountered a sibling case of Meckel's diverticulum in 9 and 11 year old Japanese boys. They were diagnosed using contrast examination and ^99mTc-pertechnetate scintigraphy before operation. The familial tendency is one in every 2500 families. Only 15 cases of familial occurence have been reported by five authors.