A new case of Ambras syndrome associated with a paracentric inversion (8) (q12; q22)

Ambras syndrome (AS) is a special form of congenital universal hypertrichosis described for the first time by Baumeister et al. (1). This form differs from other forms of congenital hypertrichosis in the pattern of hair distribution and its associated anomalies. The molecular-genetic cause of AS is unknown; the association of AS with a pericentric inversion (8) (p11.2; q22) described in the case of Baumeister so far has been unique in the literature. This report is the tenth with clinical signs of AS so far described in the literature and the second with an inversion in chromosome 8 and the first with evaluation of peripheral androgens. The new-born girl presented with abundant and dark hair on the face and ears, on the shoulders and on the arms; the other parts of the body were covered with fine, lightly pigmented hair. The face showed many dysmorphic features. Chromosome analysis showed a paracentric inversion of one chromosome 8. The breakpoints were localised at q12 and q22. The parental karyotypes were normal. Laboratory investigation showed normal plasma levels of testosterone, androstenedione (A), 17-hydroxyprogesterone, dehydroepiandrosterone-sulphate (DHA-S), free testosterone (FT), dihydrotestosterone (DHT) and 3α-androstanediol-glucuronide (3AG). Here we report a chromosomal inversion similar to that found previously not associated with alterations in androgen plasma levels.     

Familial syndrome with some features of the Langer-Giedion syndrome, and paracentric inversion of chromosome 8, inv 8 (q11.23<q21.1)

A family is reported with an autosomal dominant inherited syndrome presenting some of the typical features of the tricho-rhino-phalangeal syndrome type II (TRP II) or Langer-Giedion syndrome. The critical region for the expression of the syndrome seems to be at band 8q24.1. In the affected members of the family reported here, anomaly of chromosome 8 was noted, involving however the proximal part of the 8 long arm, which was interpreted as a paracentric inversion. Whether the anomaly is causally or only casually related to the syndrome is a matter of discussion.     

A 47,XXY fetus conceived after ICSI of spermatozoa from a patient with non-mosaic Klinefelter's syndrome: case report

The birth of 12 healthy infants to fathers with non-mosaic Klinefelter's syndrome has been reported so far. The spermatozoa for these pregnancies was obtained from frozen-thawed ejaculate in one pregnancy (twins) and from the testis in the remaining 10 infants. All of them had a normal karyotype. We describe a patient with non-mosaic Klinefelter's syndrome from whom a testicular biopsy was obtained and motile spermatozoa were collected. Of 16 oocytes that were injected, 14 fertilized and cleaved. Three embryos were transferred, resulting in a triplet pregnancy. Karyotype analysis from chorionic villous sampling revealed 46,XX, 46,XY and 46,XXY from the three fetuses. The affected 46,XXY fetus was reduced on the 14th gestational week. The pregnancy culminated with the birth of a healthy male and female, on the 36th gestational week, weighing 3600 and 2660 g respectively. This case report proves the presence of hyperploid spermatozoa in the seminiferous lumen, and strengthens the necessity of genetic diagnosis of the embryos or fetuses in such pregnancies to fathers with non-mosaic Klinefelter's syndrome.     

PGD in 47,XXY Klinefelter's syndrome patients

The use of ICSI has been a major breakthrough in the treatment of male infertility. Even azoospermic patients with focal spermatogenesis in the testis, may benefit from the ICSI technique in order to father a child. As ICSI use has become more common, centres have introduced infertility treatment for Klinefelter patients. To date, 34 healthy children have been born using ICSI without PGD, and the conception of one 47,XXY fetus has been reported. In view of the possible risk of an increased gonosome number in the spermatozoa of Klinefelter patients, a safer approach--offering these couples ICSI combined with PGD--has been used, and has resulted in the birth of three healthy children. Couples in which the male suffered from Klinefelter's syndrome were first treated in 1995; these patients were offered ICSI + PGD using FISH technology, notably to enumerate the X and Y chromosomes. ICSI + PGD was performed in 32 cycles of 20 couples with spermatozoa originating from a fresh ejaculate (n = 1), testicular biopsy (n = 21) or frozen-thawed testicular biopsy (n = 10). Normal fertilization occurred in 56.0 +/- 22.4% of the successfully injected oocytes. On day 3 of development, 119 embryos from 29 cycles were of sufficient quality to undergo biopsy and subsequent PGD; a positive result was obtained in 113 embryos. Embryos were available for transfer in 26 cycles, with a mean of 1.6 +/- 0.6 embryos per transfer. Eight pregnancies were obtained, and five resulted in a delivery. A total of 113 embryos from couples with Klinefelter's syndrome was compared with 578 embryos from control couples with X-linked disease where PGD was used to determine gender. A significant fall occurred in the rate of normal embryos for couples with Klinefelter's syndrome (54.0%) compared with controls (77.2%). Moreover, a significantly increased risk of abnormalities was observed for sex chromosomes and autosomes; for each autosome separately, this reached significance level for chromosomes 18 and 21 only. Hence, a cautious approach is warranted in advising couples with non-mosaic Klinefelter's syndrome. Moreover, the use of ICSI + PGD or prenatal diagnosis should be carefully considered.     

湛江地区85例Klinefelter综合征染色体分析

对湛江地区85例Klinefelter综合征进行了染色体分析,典型Klinefelter综合征占78％;嵌合型占14％;伴有其它染色体异常者占4％;超X线占4％。讨论了本地区Klinefelter综合征的细胞遗传学病因及其各种类型染色体异常核型与表型的关系。     

Prenatal detection of de novo paracentric inversion 46, XX inv (14) (q22q32.1) in a normal child: Report and review of the literature

We present prenatal diagnosis and follow-up examination of an individual with a de novo paracentric inversion of the long are of chromosome 14. A literature search documented 19 other cases of paracentric inversion of 14q. The outcome of each of these cases is specified together with that of this current case. Four of the 20 cases, all XY, manifested significant abnormalities with mental retardation and microcephaly present in 3 of the 4 cases; 15% (2/13) of familial cases had abnormalities and 40% (2/5) of de novo cases had abnormalities. © 1993 Wiley-Liss, Inc.     

A patient with a 47, XXY,5p- karyotype

A case is reported of a liveborn with the karyotype 47, XXY,5p -. This is the first known case of a liveborn with apparently both Klinefelter and Cri du Chat syndromes.     

Boy with 47,XXY,del(15)(q11.2q13) karyotype and Prader-Willi syndrome: a new case and review of the literature

We report on two patients with a unique constellation of anomalies resembling the Nager acrofacial dysostosis syndrome. Clinical manifestations which differentiate their condition from Nager syndrome include: microcephaly, cleft lip and palate, a peculiar beaked nose, blepharophimosis, microtia, symmetrical involvement of the thumbs, and great toes and developmental delay. We postulate that the inheritance is autosomal recessive on the basis of similarly affected male and female sibs.     

Paracentric inversion of the X chromosome [inv(X)(q12q28)] in familial FG syndrome

FG syndrome is an X-linked incomplete recessive condition comprising mental retardation, congenital hypotonia, macrocephaly, a distinctive facial appearance, and constipation or anal malformations. Here, we report on a chromosome X inversion [inv(X)(q12q28)] in a boy with FG syndrome and in his mentally retarded maternal uncle, and we discuss the possible involvement of this paracentric inversion in the FG syndrome. Am. J. Med. Genet. 86:112–114, 1999. © 1999 Wiley-Liss, Inc.     

Clinical delineation of a patient with trisomy 12q23q24

Trisomies of 12q23q24 have been described rarely in literature. Only a few case-reports have been published so far almost exclusively reporting on neonates or young infants. We present a 16-year-old patient with a trisomy of 12q23.3q24.3. Full phenotypic evaluation at this age comprised: severe growth retardation, developmental delay, intellectual disability and characteristic facial dysmorphisms. Initially, in the proband an insertion was cytogenetically mapped at chromosome 16: der(16)dir ins(16; 12)(q12.1; q24.11q24.31). The mother appeared carrier of a balanced insertion. Subsequent SNP-array analysis in the proband revealed a 16.3 Mb gain of 12q23.3 → 12q24.31. The clinical and molecular findings in this patient are compared with previous literature on cases with overlapping isolated 12q trisomies. The common phenotype observed consists of severe growth retardation, intellectual disability and characteristic facial features with hypertelorism, flat nasal bridge, down-turned mouth and poorly lobulated/low set ears. In addition, pediatric follow up into adolescence showed feeding difficulties requiring gastric tube feeding, recurrent otitis media, progressive contractures of joints and genito-renal problems, speech, communication and behavioral problems. These symptoms should be taken into account in the care and management of children with this condition.     

Jacobsen Syndrome and Beckwith-Wiedemann Syndrome Caused by a Parental Pericentric Inversion inv(11)(p15q24)

Here we report on a male infant presenting the typical pattern of Jacobsen syndrome including trigonocephaly, thrombocytopenia, congenital heart defect, urethral stenosis, and partial agenesis of the corpus callosum. Conventional karyotyping, FISH, SKY and CGH analyses showed that the region distal to the MLL locus on 11q23 was lost and replaced by the distal region of 11p, leading to a partial trisomy of 11p and a partial monosomy of 11q. According to ISCN (1995) the karyotype can be described as 46,XY,add(11)(q2?3). ish 11ptel(D11S2071x3),11qtel(VIJyRM2072x1). Array‐CGH analysis allowed us to narrow down the breakpoints to 11p15.1 and 11q24.1. Methylation analyses of genes located on 11p showed an increased level of the non‐methylated paternal allele of the KCNQ1OT1 gene, confirming the concomitant presence of Beckwith‐Wiedemann syndrome (BWS). The phenotype resulting from the 11q deletion seems to dominate the phenotype due to the distal 11p trisomy. Investigation of the parents revealed that this chromosomal rearrangement was caused by a paternal pericentric inversion inv(11)(p15q24). Since chromosomal aberrations like the one described here can easily be overlooked during routine chromosome analysis, combined FISH analysis using subtelomeric and possibly additional probes should be applied if there is any doubt about the integrity of telomeric regions.     

Patient with del(12)(q12q13.12) manifesting abnormalities compatible with Noonan syndrome

We report on a Japanese boy with interstitial deletion of chromosome 12q12–q13.12, who had multiple congenital anomalies with severe psychomotor retardation. Most of the clinical manifestations were compatible with Noonan syndrome phenotype except for the absence of cardiac defects. Severe mental retardation and intrauterine onset of growth retardation may have been due to the chromosomal deletion. The interstitial deletion does not overlap a putative Noonan syndrome locus, which was recently assigned to 12q22–qter by linkage analysis. Although correlation between the phenotype and del(12)(q12q13.12) was not confirmed, because this is the first report of deletion of proximal 12q, the deleted segment may contain another Noonan syndrome locus. Am. J. Med. Genet. 75:416-418, 1998. © 1998 Wiley-Liss, Inc.     

Agenesis of the corpus callosum in Schinzel-Giedion syndrome associated with 47, XXY karyotype

The Schinzel-Giedion syndrome is a rare autosomal recessive condition with typical facial features, skeletal manifestations and congenital hydronephrosis and/or hydroureter. We report a male infant with Schinzel-Giedion syndrome, also showing the karyotypic abnormality 47, XXY. Agenesis of the corpus callosum and laryngeal stenosis were determined at autopsy. Besides typical Schinzel-Giedion syndrome, our propositus was found to be affected by Klinefelter syndrome. This represents a fortuitous anomaly, which is probably of no importance in the phenotype of the patient.     

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.     

Genetics: Testicular sperm recovery in nine 47,XXY Klinefelter patients

Klinefelter's syndrome is generally characterized by hyper-gonadotrophichypogonadism and azoospermia. The clinical features, however,are variable, and occasionally severe oligozoospermia may bepresent Usually in these cases a 46,XY/47,XXY mosaic karyotypeis involved. However, focal spermatogenesis and severe oligozoospermiahave been reported in 47,XXY individuals too. In the presentstudy we investigated whether testicular spermatozoa can berecovered in 47,XXY patients with a view to intracyto-plasmicsperm injection (ICSI). In four out of nine apparently non-mosaic47,XXY patients, spermatozoa were recovered from the wet preparationsof testicular tissue and ICSI was performed in three couples.In one patient in whom spermatozoa were successfully recoveredand used for ICSI, no spermatozoa were retrieved at a secondtrial. Although these results show that in some 47,XXY individualstesticular spermatozoa can be successfully recovered and evenused for ICSI, at present this approach should be consideredexperimental. There may indeed be some concern about the chromosomalnormality of the embryos generated through this infertilitytreatment Patients with Klinefelter's syndrome should thereforebe counselled about the complexity of this treatment, whichinvolves multiple testicular biopsies from hypogonadal testes,ICSI and preimplantation diagnosis by fluorescence-in-situ hybridization.     

A 15q24 microduplication, reciprocal to the recently described 15q24 microdeletion, in a boy sharing clinical features with 15q24 microdeletion syndrome patients

A 15q24 microduplication, reciprocal to the minimal critical region for the recently described 15q24 microdeletion syndrome, was found in a 2-year-old boy by 244k Agilent oligoarray CGH analysis. The boy had global developmental delay and dysmorphic facial features, digital and genital abnormalities. The duplication was inherited from a healthy father, but was considered clinically significant, as the patient shared clinical features with 15q24 microdeletion syndrome patients. To our knowledge this is the first report of a patient with a 15q24 microduplication.     

Prader-Willi syndrome with a karyotype 47,XY,+min(15)(pter->q11.1:) and maternal UPD 15--case report plus review of similar cases

Prader-Willi (PWS) and Angelman (AS) are syndromes of developmental impairment that can result either from a 15q11-q13 deletion, paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. A small cytogenetic subset of PWS and AS patients are carriers of a so-called small supernumerary marker chromosome (sSMC). Here, we report on an previously unreported PWS case with a karyotype 47,XY,+min(15)(pter->q11.1:) plus maternal heterodisomic UPD 15. A review of the literature revealed, that for both, PWS and AS patients, cases with (1) a sSMC plus microdeletion of the PWS/AS critical region, (2) inv dup(15) plus uniparental disomy (UPD) 15 and (3) cases without exclusion of a microdeletion an UBE3A mutation or UPD are described. The present case as well as the review of similar cases provides further evidence for the necessity to test UPD in prenatal cases with a de novo sSMC and in postnatal cases with otherwise unexplainable clinical phenotype.     

An XYY boy with short stature and a case of Klinefelter's syndrome (XXY) in a family with inversion 9

A patient with Klinefelter's syndrome and a boy with XYY sex chromosomes were both found to have a pericentric inversion of chromosome 9. An unusual feature of the XYY patient was that he presented because of short stature and disturbed behaviour. A family study showed that the patients were related and that there was an excess of males in the pedigree. Another member of the family was found to have some XYY cells in the blood.