Jacobsen distal 11q deletion syndrome with a myelodysplastic change of hemopoietic cells

We describe a male infant with unusual facial appearance, relative pancytopenia, bilateral simian creases, and an accessory nipple. Cytogenetic analysis showed deletion of the long arm of chromosome 11 [46,XY,del(11)(pter→q23.2:)]. Bone-marrow study showed a myelodysplastic change of hemopoietic cells compatible with peripheral blood findings. Pachygyria of the temporal and frontal lobes was demonstrated by magnetic resonance image (MRI) of the brain. We present our findings in order to contribute to the information on 11q23 deletion. Am. J. Med. Genet. 75:341-344, 1998. © 1998 Wiley-Liss, Inc.     

Familial t(11;13)(q21;q14) and the duplication 11q, 13q phenotype

Cases of duplication of distal 11q or proximal 13q have been reported independently. A specific translocation resulting in duplication of distal 11q, [der(22)t(11;22)(q23;q11)], has been documented in over 40 cases. We report on a male fetus with chromosomal excess of both distal 11q and proximal 13q resulting from a familial translocation. This case supports the causal association of duplication 11q with neural tube defects. © 1993 Wiley-Liss, Inc.     

Interstitial deletion 2q31→q33

We present an 8-month-old female with severe retardation of growth and development, multiple congenital anomalies, and an interstitial deletion del(2)(q31→q33) including results of cytogenetic and gene marker studies. The manifestations of this infant are compared with those of four other known patients with a partial del(2q).     

Identification and molecular characterization of a small 11q23.3 de novo duplication in a patient with Rett syndrome manifestations

We report on an interstitial duplication of the long arm of chromosome 11 [46,XX,dup(11)(q23.3)] in a girl with atypical Rett syndrome (RS). This case was discovered during a systematic cytogenetic study of RS. Fluorescent in situ hybridization including total chromosome painting and use of regional specific YAC, cosmid and plasmid probes, was used to confirm the chromosome 11q involvement and to identify the landmarks of the smallest 11q duplication reported to date. The findings are compared to cases of trisomy 11q reported previously, all of which have a larger duplication and different clinical manifestations. Surprisingly, mental retardation and behavior disorders are less severe in these cases. Am. J. Med. Genet. 80:273–280, 1998. © 1998 Wiley-Liss, Inc.     

MCA/MR syndrome with features of Hallermann-Streiff syndrome and 4q deficiency/ 14q duplication

Fryns JP, Borghgraef M, Lemmens F, Van den Berghe H. MCA/MR syndrome with features of Hallermann-Streiff syndrome and 4q deficiency/14q duplication.
Clin Genet 1993: 44: 146–148. © Munksgaard, 1993
In this report we present the clinical history and findings in a female newborn with 4q deficiency/14q duplication, the unbalanced product of a paternal t(4;14)(q33;q32). The clinical symptoms and signs observed in this child up to the age of 14 months were most compatible with the diagnosis of Hallermann-Streiff syndrome.     

Malformation syndrome of duplication 12q24.1→qter

While duplication and deletion of the short arm of chromosome 12 cause well-recognized syndromes, duplication of the long arm of chromosome 12 is rarely observed. We are reporting a duplication of chromosome 12 distal to band q24.1 in a five-month-old child. His chromosome constitution is 46,XY,-4, + der(4),t(4:12)(p16;q24.1)mat. The balanced translocation is also carried by his maternal grandmother and two of the mother's brothers. The malformation syndrome consisted of unusual facial appearance and anomalies of the musculoskeletal, cardiovascular, genitourinary, and central nervous systems. Four previously reported patients had similar break points on chromosome 12 with similar malformations; therefore, phenotype-karyotype correlation suggests a definitive malformation syndrome associated with duplication of chromosome region 12q24.1→qter.     

Duplication 18q syndrome

Some variation in the phenotype of patients with dup(18q) is recognized. Our patient has the phenotype described for dup(18qter).     

New MCA/MR syndrome with generalized hypotonia,congenital hydronephrosis,and characteristic face

We have observed a newly recognized syndrome in two unrelated Japanese patients. Manifestations include severe mental retardation, growth failure, generalized floppiness, congenital hydronephrosis, cardiac anomalies, cleft palate, and characteristic face. To date, caused genesis is unknown. Am. J. Med. Genet. 68:347–349, 1997. © 1997 Wiley-Liss, Inc.     

Pseudoachondroplasia with de novo deletion [del(11)(q21q22.2)]

Pseudoachondroplasia (PSACH) is a relatively common osteochondrodysplasia characterized clinically by short-limbed short stature with normal face, and radiographically by platyspondyly and dysplasias of epiphyses and metaphyses of the tubular bones. Recently, mutation of cartilage oligomeric matrix protein has been identified in PSACH. However, clinical variability and genetic heterogeneity have been reported in PSACH, indicating a possible existence of a second PSACH gene. Here, we report on a patient with a typical severe form of PSACH who had a de novo interstitial deletion in the long arm of chromosome 11 [del(11)(q21q22.2)]. The size of the deletion was estimated at 0.8–7.3 Mb using fluorescent in situ hybridization (FISH). This deletion may contain or disrupt a second PSACH locus. Am. J. Med. Genet. 77:356–359, 1998. © 1998 Wiley-Liss, Inc.     

Cerebro-facio-articular syndrome of Van Maldergem: confirmation of a new MR/MCA syndrome

Van Maldergem et al. (1992) described a new syndrome in an 11-year-old girl, characterized by: mental retardation, hypotonia, dysmorphic facies with telecanthus, epicanthus, broad flattened nose, large inverted W-shaped mouth, malformed ears, finger camptodactyly, and joint hyperlaxity. In this report we present a 5-year-old girl with very similar clinical findings. We confirm the existence of this condition as an independent clinical entity, and we propose that, based on the major clinical manifestations, it should be defined as "cerebro-facio-articular" syndrome.     

Ring-11 chromosome: Phenotype-karyotype correlation with deletions of 11q

The cytogenetic evaluation of a female infant with congenital anomalies led to the identification of the second reported case of a ring-11 chromosome. Unlike the previously described case, in which the patient had only minimal clinical findings and no demonstrable loss of material from the ring, our patient had numerous anomalies that were asssociated with a substantial deficiency of 11q material. The different phenotypes in these two cases represent variation in the amount and location of the chromosomal material lost during the genesis of the ring. The manifestations of this patient and the deletion of region q24→qter from the ring-11 identify a specific chromosome deletion syndrome referred to as del (11q) syndrome.     

A deletion 13q34/duplication 14q32.2-14q32.33 syndrome diagnosed 50 years after neonatal presentation as infantile hypercalcemia

During infancy, this 50‐year‐old man with a previously undiagnosed multiple congenital anomalies/intellectual disability (MCA/MR) syndrome had grossly symptomatic hypercalcemia and was (briefly) thought to have Williams syndrome. Results of studies with the cytogenetic methods of the 1960s and 1970s were apparently normal. He matured late, but is high‐functioning and healthy. Over 50 years he remained a diagnostic enigma. Thus, it came as a surprise when recent high‐resolution banding methods showed an abnormality of the terminal portion of 13q, determined on array‐comparative genomic hybridization to constitute an unbalanced chromosome rearrangement with a 0.35 Mb loss of 13q34‐ter and 7.67 Mb gain of 14q32.2q32.33 translocated to 13q34. This apparently de novo genomic abnormality must be presumed as the cause of this previously undescribed MCA/MR syndrome which, however, may remain a private syndrome in this family. Williams syndrome was ruled out, and presently it is not possible to ascribe this patient's severely symptomatic infantile hypercalcemia to any gene on the deleted or duplicated chromosome segments. This “case” does underscore the importance of re‐studying previously obscure but evidently genetic conditions, of long‐term follow‐up and documentation of natural history, and of providing, at last, a causal explanation to the family. © 2011 Wiley‐Liss, Inc.     

Two concurrent chromosomal aberrations involving interstitial deletion in 1q24.2q25.2 and inverted duplication and deletion in 10q26 in a patient with stroke associated with antithrombin deficiency and a patent foramen ovale

Advanced high-throughput molecular cytogenetic analysis has enabled the identification of small chromosomal rearrangements, and two or more concurrently occurring chromosomal rearrangements have been identified using this technique. A girl with severe psychomotor developmental delay associated with an uncertain abnormality (detected by conventional karyotyping) in chromosome 10q had a sudden stroke at the age of 35 months. Laboratory and radiographic examinations revealed antithrombin (AT) deficiency and a patent foramen ovale (PFO). Two concurrent chromosomal aberrations, inverted duplication and deletion in the 10q26 region and a microdeletion in the 1q24.2q25.2 region including the AT gene (SERPINC1), were identified by microarray-based comparative genomic hybridization analysis. Both chromosomal aberrations were found to be of paternal origin. This study described the concurrence of chromosomal rearrangements involving two chromosomes, and estimated the frequency of two or more chromosomal aberrations as 2-4%.     

Unusual cytogenetic mosaicism involving chromosome 14 abnormalities in a child with an MR/MCA syndrome and abnormal pigmentation

An 8-year-old female child with mental retardation (MR), multiple congenital anomalies (MCA) and irregular pigmentation was shown to have karyotypic mosaicism involving chromosome 14 abnormalities. Four cell lines were found in both peripheral blood lymphocytes and skin fibroblasts and were represented by: a normal karyotype, an isopseudodicentric 14q [iso psu dic(14)], a ring 14 [r(14)], and a monosomy 14 [mono(14)]. Our results are compared with reported cases involving multiple abnormalities of specific chromosomes. Karyotypic mosaicism of comparable chromosome 14 abnormalities is rare, with only one known previous case. Detailed analysis of karyotypic mosaicism of rare chromosomal abnormalities is essential to determine meaningful correlations with specific patterns of malformation.     

Newly recognized autosomal recessive MCA/MR/ overgrowth syndrome

We report on two sibs, born to nonconsanguineous parents, presenting with mental retardation, overgrowth, craniosynostosis, distal arthrogryposis, sacral dimple, and joint laxity. These patients may have a previously undescribed autosomal recessive syndrome. © 1993 Wiley-Liss, Inc.     

A new genomic duplication syndrome complementary to the velocardiofacial (22q11 deletion) syndrome

Fluorescence in situ hybridization (FISH) analysis can reveal undetected chromosomal rearrangements. We report a patient with cleft palate, hydronephrosis, and minor dysmorphic features, including low-set posteriorly rotated ears, down-slanting palpebral fissures, mandibular micrognathia, and brachymesophalangia. Routine chromosome analysis identified no abnormality of chromosome 22; FISH analysis with the TUPLE1 probe disclosed an interstitial duplication of 22q11.2. FISH analysis did not reveal the duplication on the initial testing of metaphase chromosomes, although, on review, the area was brighter on one chromosome in each metaphase spread. FISH analysis of interphase cells showed three TUPLE1-probe sites with two chromosome-specific identification probes in each cell. Family history showed two older full siblings, a brother with behavior problems, oppositional defiant disorder, and learning problems and a sister with hydronephrosis and mild delays. The father and both siblings had similar facial features, and all three had the same interstitial duplication of the TUPLE1 probe. This family illustrates the novel complementary duplication syndrome of the velocardiofacial syndrome, which adds it to the expanding list of genomic deletion/duplication syndromes. The laboratory results further show the utility and need for careful analysis of interphase cells even in samples where good quality metaphases are available.     

Supernumerary inv dup(15) in a patient with Angelman syndrome and a deletion of 15q11–q13

We have studied a patient with Angelman syndrome (AS) and a 47,XY,+inv dup(15) (pter→q11::q11→pter) karyotype. Molecular cytogenetic studies demonstrated that one of the apparently normal 15s was deleted at loci D15S9, GABRB3, and D15S12. There were no additional copies of these loci on the inv dup (15). The inv dup (15) contained only the pericentromeric sequence D15Z1. Quantitative DNA analysis confirmed these findings and documented a standard large deletion of sequences from 15q11-q13, as usually seen in patients with AS. DNA methylation testing at D15S63 showed a deletion of the maternally derived chromosome. AS in this patient can be explained by the absence of DNA sequences from chromosome 15q11-q13 on one of the apparently cytogenetically normal 15s, and not by the presence of an inv dup (15). This is the fourth patient with an inv dup (15) and AS or Prader Willi syndrome, who has been studied at the molecular level. In all cases an additional alteration of chromosome 15 was identified, which was hypothesized to be the cause of the disease. Patients with inv dup (15)s may be at increased risk for other chromosome abnormalities involving 15q11-q13. © 1995 Wiley-Liss, Inc.     

Deletion of (11)(q24.2) in a mother and daughter with similar phenotypes

A del(11) (q24.2) was ascertained in a 2-year-old child and subsequently in her 20-year-old mother. Both mother and daughter had developmental delay, short stature, and “coarse” facial appearance. We compare our patients' manifestations to those associated with the distal 11q2 deletion phenotype (“Jacobsen” syndrome), and to the one other reported case of del(11)(q24.2). Our patients did not resemble this latter case, but had some findings in common with Jacobsen syndrome. We present our findings in order to contribute to the information on 11q2 deletions. © 1994 Wiley-Liss, Inc.