Michelin tire baby syndrome: familial constriction bands during infancy and early childhood in four generations.

We report on an infant with an unusual pattern of transitory familial constriction bands distributed symmetrically and circumferentially over the neck, forearms, and lower legs. Family history showed the occurrence of similar bands among individuals in 4 generations transmitted as an autosomal dominant trait. Neck and limb distribution in the other affected family members was also symmetrical and circumferential, with spontaneous resolution taking place during childhood. This case represents another example of the Michelin tire baby syndrome, also known as multiple benign circumferential skin creases of the limbs, and further demonstrates its autosomal dominant mode of inheritance.

Osteopathia striata syndrome. Clinical, genetic and radiologic considerations.

Osteopathia striata, an autosomal dominant disorder, has been diagnosed in a 19-year-old mildly retarded woman. In addition, she has macrocephaly, a leonine facies, disfigurement of the lower jaw, a cleft palate and mixed hearing loss. Roentgenograms of the skull and long bones show thickening of the calvarium, particularly at the base, mandibular hyperplasia, and striations in the long bones and pelvis. Except for the cleft palate, which has not been previously reported, and the retardation, which appears to be quite uncommon in this condition, these findings are characteristic of osteopathia striata. Because the disorder may resemble several other conditions, the differential diagnosis should include osteopoikilosis, the autosomal dominant form of osteopetrosis, and hyperostosis corticalis generalisata.

Two balanced translocations in three generations of a pedigree: t(7;10) (q11;q22) and t(14;21) (14qter to cen to 21qter)1.

A reciprocal chromosome translocation between 7q and 10q and an unrelated Robertsonian translocation involving 14q and 21q were found in a healthy 44-year-old man, in his normal 18-year-old son, and in his mother. They were ascertained through the man's brother, whose grandson has Down's syndrome as a result of an inherited 14q21q translocation. To our knowledge, this is the second report of a karyotype with both reciprocal and Robertsonian translocations in a single subject, and only the fourth report of independently segregating double translocations occurring in more than one generation.

Evidence from somatic cells for crossing-over in humans.

Chromosomal and gene marker studies of somatic cells in a family with multiple chromosome translocations show apparent instability of the translocations in transmission from generation to generation. This instability is attributed to meiotic crossing-over between the involved chromosomes. Technical advances in chromosome analysis combined with human gene map information in the study of this unusual family demonstrate for the first time that crossing-over involves exchange of chromatin between nonsister chromatids of homologous chromosomes.

47,XX,+der(18),t(9;18)(p24;q21) mat: a distinct partial trisomy 18q--syndrome?

A moderately retarded girl had a 47,XX,+der(18),t(9;18)(p24;q21)mat abnormality that was inherited from her mother, who had a 46,XX,t(9;18)(p24;q21) karyotype in most cells, and a minor cell line of 47,XX,+der(18),-t(9;18)(p24;q21). Her dysmorphic features--bilateral epicanthic folds, low-set, abnormal ears, low posterior hairline, clinodactyly of the 5th fingers, and broad great toes--were similar to those of other patients with an additional number 18 chromosome in which all or most of the long arm was missing, thus raising the possibility of a distinct syndrome.

10q(q23 leads to qter) duplication: GOTs, HK1, and other gene markers.

Gene marker analyses have been carried out in a patient with 10q(q23 leads to qter) duplication. The observed elevation of red cell glutamic oxaloacetic transaminase activity is compatible with earlier somatic cell hybridization studies that mapped the locus to this region. Hexokinase-1 activity in the red cells was normal,which is consistent with its prior assignment to the unaffected part of chromosome 10(10pter leads to q23).

Features of trisomy 18 and 18p- syndromes in an infant with 45,XY,i(18q).

An isochromosome for the long arm of chromosome number 18 - 46,XY,i(18q) - was found in an infant who had features of both trisomy 18 and 18p- syndromes. Findings compatible with trisomy 18 included postmature delivery, prominent occiput, severe congenital heart disease, overlapping fingers, and rocker-bottom feet. Those of 18p- syndrome, which frequently resembles Turner syndrome, were downward obliquity to the palpebral fissures, short, webbed neck, low posterior hairline, and widely-spaced nipples. The infant died of heart failure at 3.5 months of age. Parental karyotypes were normal.

A 45,XX,-5,-14,+t(5q;14q)mat cri du chat child.

A two-year-old girl has the following features of the cri du chat syndrome: microcephaly, hypertelorism, downward slanting of the palpebral fissures, psychomotor retardation and a cat-like cry. She is only of five patients having the cat cry syndrome with 45 chromosomes. Her karyotype is 45,XX, -5, -14, +t(5; 14)(5qter leads to 5p11: : 14q11 leads to 14qter) with the translocation inherited from her mother and maternal grandmother, each of whom is the carrier of a balanced translocation 46,XX,t(5;14)(p11q11). Normal plasma activity for hexosaminidase B suggests the locus for this enzyme is not located in the delected segment of 5 p.

Trisomy 18 mosaicism: clues to the diagnosis.

Karyotypes of blood and skin fibroblasts at ages 3 and 8.5 years had shown non-mosaic trisomy 18 in a male now of age 19. Because of his prolonged survival and an atypical phenotype, skin fibroblast cultures from a new biopsy were established at age 18, and only normal 46,XY cells were observed, while peripheral blood lymphocytes still demonstrated 47,XY, + 18. This patient and six others with trisomy 18 mosaicism illustrate the advisability of looking for such a pattern in individuals whose phenotype in early life is not fully consistent with the trisomy 18 syndrome. Additional clues to the presence of trisomy 18 mosaicism are male sex, survival beyond 2 years and lack of fingertip arches.

Miller-Dieker syndrome. Detection of a cryptic chromosome translocation using in situ hybridization in a family with multiple affected offspring.

OBJECTIVE: To describe a family in whom fluorescence in situ hybridization allowed for accurate diagnosis of Miller-Dieker syndrome in an at-risk pregnancy and determination of parental carrier status. DESIGN: Retrospective case analysis and application of a new molecular tool to evaluate the family. SETTING: Health maintenance organization. The family was followed up by the Departments of Medical Genetics, Pediatrics, and Obstetrics and Gynecology, Kaiser Permanente Medical Center, Panorama City, Calif. PARTICIPANTS: Members of a single family. INTERVENTIONS: Clinical evaluation and neuroimaging studies of the proband. Prenatal diagnosis via ultrasonography and amniocentesis. Chromosomal evaluation of the couple and their offspring. In situ hybridization studies in both parents and an affected fetus. MEASUREMENTS/MAIN RESULTS: We describe a family in whom fluorescence in situ hybridization detected a submicroscopic deletion of the Miller-Dieker syndrome critical region 17p13.3 arising from a cryptic translocation in one of the parents. The proband was determined at birth owing to the presence of multiple congenital anomalies, including low birth weight, microcephaly, agenesis of the corpus callosum, lissencephaly, cerebral atrophy, unilateral ptosis, polydactyly, and omphalocele. High-resolution chromosome-banding analysis findings were normal in the parents and proband, who died at age 4 years. There were four subsequent pregnancies: two ended in first-trimester spontaneous abortion, and in the other two, large omphaloceles were detected in fetuses at 15 and 13 weeks' gestation. Both pregnancies were terminated. Fluorescence in situ hybridization probes for 17p13.3 had become available before the most recent pregnancy and were used to study parental and fetal cells. As a result, a balanced cryptic translocation between chromosome 17 and chromosome 19 was identified in the father: 46,XY,t(17;19)(p13.3q13.33). An unbalanced form of the translocation, involving a deletion of 17p13.3, was detected with fluorescence in situ hybridization in the fetus. This finding was in accordance with a clinical diagnosis of Miller-Dieker syndrome. CONCLUSIONS: Molecular cytogenetic technology should be used in cases of suspected Miller-Dieker syndrome when high-resolution cytogenetic analysis fails to detect del(17) (p13.3). Positive findings should be followed up with parental studies. In addition, omphalocele should be included among the list of malformations that make up the Miller-Dieker syndrome.

Association of generalized dystrophic epidermolysis bullosa with positive acetylcholinesterase and markedly elevated maternal serum and amniotic fluid alpha-fetoprotein.

A case of fatal generalized dystrophic epidermolysis bullosa is described in a prematurely born female whose mother had strikingly elevated mid-trimester serum and amniotic fluid alpha-fetoprotein concentrations, a positive amniotic fluid acetylcholinesterase band, and negative serial ultrasound studies. This case lends further support to an association between autosomal recessive generalized dystrophic epidermolysis bullosa and increased levels of alpha-fetoprotein, positive amniotic fluid acetylcholinesterase, and normal ultrasound findings.

A family with three independent autosomal translocations associated with 7q32----7qter syndrome.

Two persons within the same family were discovered to be trisomic for the segment 7qter. However, several features differed from those described in other patients with this syndrome, for example, normal birth weight and neck size, cleft palate, and beaked nose. In addition to the phenotypic variation, there were three independently segregating autosomal translocations in the pedigree: t(1;7)(q43;q32), t(1;6) (p22.3;q14.1), and t(3;10)(q26.1;p11.21). This is a finding that, to our knowledge, has not been previously reported.

Persistently elevated AFP and AChE in amniotic fluid from a normal fetus following demise of its twin.

Intrauterine fetal demise (IUFD) in one of twins at 12 weeks of gestation was accompanied by markedly elevated maternal serum alpha-fetoprotein (AFP) at 17 and 18 weeks. Amniotic fluid AFP from the healthy surviving twin's sac at 18.5 and 23 weeks was also greatly increased along with a positive acetylcholinesterase (AChE) band. Persistently elevated AFP and positive AChE so long after fetal demise--6.5 and 11 weeks post IUFD--has not, to our knowledge, been previously described. In similar cases, high level ultrasound and careful placental examination at birth should be utilized to search for fetal abnormalities or multiple pregnancy with IUFD.

Attitudes toward genetic carrier screening for cystic fibrosis among pregnant women: the role of health beliefs and avoidant coping style.

In this study we examined the relations among psychosocial factors associated with pregnant women's attitudes toward genetic carrier testing for cystic fibrosis (CF). A sample of 511 pregnant women attending various health clinics for general prenatal care were educated about CF. Women's health beliefs, coping styles, and attitudes toward CF carrier screening were assessed. Results from structural equation modeling analyses indicated that women who perceived themselves as more likely to be carriers of the CF gene and who perceived greater benefits of screening were positively inclined toward genetic screening. Perceived barriers to screening were negatively associated with women's attitudes toward CF genetic testing. In addition, the findings suggest that some types of avoidant coping styles may indirectly influence one's decision to undergo genetic screening through perceptions of risk, benefits, and barriers. Given the advent of genetic screening options for many diseases, in this study we address some issue in women's attitudes toward prenatal screening that are relevant to a variety of genetic screening programs.