Chromosome studies in 1792 males prior to intra-cytoplasmic sperm injection: the Dutch experience.

The chance of a male with severe oligozoospermia or azoospermia achieving a pregnancy has undergone a revolutionary increase with the introduction of the intracytoplasmic sperm injection technique (ICSI). However, since ICSI circumvents part of the natural sperm selection mechanisms, the possible transmission of genetic defects to the offspring is a major concern. Cytogenetic analysis is a relatively simple technique to identify at least the carriers of a chromosomal aberration before starting the ICSI procedure. In order to assess the frequency of chromosomal aberrations in male ICSI candidates, we have performed a nationwide cytogenetic study. Of the 1792 males examined, 72 (4.0%) revealed a chromosomal aberration, and one individual even had two. Numerical sex chromosomal aberrations and Robertsonian translocations predominated, followed by reciprocal translocations, inversions and supernumerary marker chromosomes. The different implications, in case a chromosomal aberration is encountered prior to ICSI, are discussed.

The Dutch Uniform Multicenter Registration system for genetic disorders and malformation syndromes.

In medical genetics, several systems are used to classify and code genetic disorders for the purpose of automated registration. In the Netherlands, a genetic diagnosis code system has been developed that links a unique four-digit code to a principal description and all current synonyms. The main goal of this coding system is to enable nationwide uniformity of coding, without losing access to information stored in the past, identified by the ICD/BPA code (the International Classification of Diseases as adapted by the British Paediatric Association) and/or the MIM code (McKusick's classification in Mendelian Inheritance in Man). To this effect, the Dutch diagnosis code is cross-referenced with the 2 pre-existing classification systems. Developments in medical genetics make regular updates of all coding systems necessary. In the Netherlands, new diagnosis codes are assigned centrally to preserve uniformity and distributed periodically to all 8 clinical genetic centers. Diagnosis codes are assigned in numerical order of inclusion, enabling quick and easy updates. It is possible to include subclassifications of disorders according to pattern of inheritance, gene location, and gene mutations and to cover all disorders and disorder subtypes which are not clearly distinguished by the 2 pre-existing classification systems. The architecture of the coding system is suitable for international use. It offers a practical solution for clinical geneticists in need of a coding system suitable for clinical use. The use of the diagnosis code will also facilitate reliable comparison of data and nationwide genetic epidemiological studies.

Intracytoplasmic sperm injection (ICSI) and chromosomally abnormal spermatozoa.

An infertile couple was referred for intracytoplasmic sperm injection (ICSI) because of primary infertility and oligoasthenoteratozoospermia (OAT) in the male. It was observed that although the sperm cells presented with an unusual head size and multiple tails they were able to fertilize the oocytes after ICSI. Subsequent molecular cytogenetic analysis demonstrated de-novo chromosome abnormalities in virtually all sperm cells with 40% diploidy and 24% triploidy in addition to aneuploidy for the sex chromosomes.

Are Down syndrome fetuses detected through maternal serum screening similar to those remaining undetected?

This study was designed to examine whether fetuses with Down syndrome (DS) identified through serum screening are different from those whose mothers have normal serum screening results. It was a retrospective follow-up study of pregnancies where maternal serum alpha-fetoprotein (MSAFP) concentrations were measured to identify women at increased risk of having a baby with a neural tube defect (NTD). An enhanced risk for NTD was the only reason for intervention in the screened population. Clinical features of fetuses or children with DS were related to the screening results. A retrospectively calculated term risk of 1/250 classified a pregnancy as having been at an elevated risk of DS. The outcome measures were fetal or neonatal death and severe somatic disease. Human chorionic gonadotrophin (hCG) and unconjugated oestriol (uE3) were measured retrospectively in frozen samples of the DS pregnancies and the same cut-off level was used for classification (so-called 'triple test'). Ten thousand women were included in the study. Pregnancy outcome was known in 93.5 per cent of the cases. Children with and without anatomic defects were found in all subgroups of test results combinations. All mothers of children with a congenital heart defect (CHD) had a DS risk of > or = 1/250 according to the triple test.

18q- and 18q+ mosaicism in a mentally retarded boy.

A mentally retarded boy was found to have an unusual chromosomal mosaicism [46,XY, del(18) (q22)/46,XY,iso psu dic(18)(q23)]. The clinical manifestations are compatible with the 18q- syndrome. The chromosome alteration was defined by high resolution banding and fluorescence in situ hybridization (FISH). A mechanism to explain the origin of the two cell lines is presented and discussed.

Congenital glaucoma in a child with partial 1q duplication and 9p deletion.

A case of partial duplication of chromosome 1 (1q41-qter) and partial deletion of chromosome 9 (9p24-pter) with infantile congenital glaucoma is reported. The histopathology of the eyes is described. The clinical findings ascribed to trisomy 1q and partial monosomy 9p are summarized and compared to this case. As this is the second report of a patient with monosomy 9p24-pter and congenital glaucoma, it may indicate localization of a gene involved in congenital glaucoma in this region of the human genome.

Interstitial deletion of the long arm of chromosome 11.

A girl with an interstitial deletion of the long arm of chromosome 11 is described. The patient was mildly mentally retarded and showed some facial dysmorphic features, including hypertelorism, ptosis, and cleft palate.

Trisomy 10 mosaicism in a newborn boy; delineation of the syndrome.

The fifth case of trisomy 10 mosaicism is presented. Only in cultured fibroblasts this mosaicism was found, while peripheral lymphocytes revealed a normal karyotype. In comparison with the literature, trisomy 10 mosaicism syndrome is further delineated compromising of failure to thrive, high forehead, hypertelorism, mongoloid eye slant, blepharophimosis, dysplastic, large ears, retrognathia, long slender trunk, marked plantar and palmar furrows, cardiopathy and early death.

Duplication in chromosome 15q in a boy with the Prader-Willi syndrome; further cytogenetic confusion.

We describe a six-year-old boy with the typical features of Prader-Willi syndrome. Cytogenetic investigation revealed a chromosome aberration that has not been described yet, i.e. a duplication in the proximal half of 15q. Based upon banding-pattern the exact nature of the duplicated part could not be delineated. Both parents had a normal karyotype. Various hypotheses concerning the relationship between Prader-Willi syndrome and various chromosome 15 abnormalities are discussed.

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 11q due to paternal t(11q;18p); further delineation of the clinical picture.

We describe an eleven-months-old girl with a partial trisomy 11q due to a paternal t(11;18)(q142;p1131). Clinical symptoms include severe psychomotor retardation, microcephaly, cleft palate, large, beaked nose, micrognathia, short hands and proximally placed thumbs. Moreover, a partial agenesis of the callosal body and a perineal mid-line malformation are present. The clinical picture of the index case is compared with relevant findings in patients with a partial trisomy (11q) and partial monosomy (18p) (Aksu 1977).

Automated selection of metaphase cells by quality.

The performance of metaphase-finding systems could be improved if they were able to determine the quality of the cells detected. This paper discusses the extent to which this may be realized by the introduction of a metaphase-quality parameter. Data obtained from 300 cells were statistically analyzed. Seventeen features were measured and nine visual properties were determined for each cell. Discriminant analysis and regression analysis were used to extract those features and visual properties which contribute to assessment of metaphase quality. Rather low correlations were found between the selected measured features and visual properties. A quality-parameter based on a linear combination of cluster projections, areas and perimeters was found to account for 64% of the variation between visual and measured quality indicators. In addition, an increase in the predictive value for finding usable metaphases from 28-68% was achieved.

Two cases with different deletions of the long arm of chromosome 7.

Two mentally and physically retarded girls, one with an interstitial deletion 7 (pter leads to q21::q32 leads to qter), and the other with an interstitial deletion 7 (pter leads to q11::q22 leads to qter), are described. Their clinical features are compared with those of 11 earlier reported cases with a deletion 7q. The Hageman factor, the locus of which is assigned to the distal part of 7q, was in both cases within normal limits. The data available do not justify the delineation of a specific clinical syndrome.

Partial trisomy 10q: a recognizable syndrome.

Five cases from two nonrelated families with partial trisomy 10q due to a reciprocal translocation t(10;17)(q25;p13) and t(10;11)(q24;q23), respectively, are reported. The phenotypic findings are compared with those of 17 previously published cases; the clinical data justify the conclusion that cases with trisomy 10q show a specific syndrome of mental retardation and malformation characterized by psychomotor retardation, growth retardation, hypotonia, high forehead, flat face, fine and arched eyebrows, antimongoloid slant of the eyes, narrow palpebral fissures, hypertelorism, short nose, bow-shaped mouth, short neck (kypho)scoliosis, and in some cases microcephaly.

Double translocation t(7;12),t(2;6) heterozygosity in one family. A contribution to the trisomy 12p syndrome.

Double translocation heterozygosity t(2;6),t(7;12) in three generations of a Dutch family is described: the segregation of a double translocation in more than one generation has not been previously published. The index case was a 16-year-old mentally retarded boy with partial trisomy 12p who showed several dysmorphic features such as high prominent forehead, flat face, flat and short nose bridge, short nose, dysplastic ears, prominent lower lip, and several skeletal abnormalities. Based on the findings in this patient and those in nine other cases, the existence of a specific trisomy 12p syndrome is postulated.

Partial trisomy 6p due to familial translocation t(6;20)(p21;p13). A new syndrome?

Cytogenetic findings in a case of partial trisomy 6p due to a translocation t(6;20)(p21;p13) and eleven balanced translocation heterozygotes are described. The clinical data of the proposita are compared with those of five other published cases. A partial trisomy 6p syndrome is postulated, characterized by: low birth weight, psychomotor retardation, craniofacial abnormalities (such as high prominent forehead, large fontanel, wide sagittal suture, blepharoptosis, low-set and/or malformed ears), congenital heart malformation, small kidneys, and proteinuria. Linkage studies have shown that the breakpoint in chromosome 6 involved in this translocation is close to the HLA gene cluster.