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.

Blepharophimosis: a causally heterogeneous malformation frequently associated with developmental disabilities.

We report on 22 individuals referred for genetic evaluation because of blepharophimosis. Fourteen of these patients had the blepharophimosis syndrome: 5 familial and 9 sporadic. Mental retardation or developmental delay was seen in 8 of the 12 children in whom this could be assessed. Eight of 22 children had a malformation syndrome other than the blepharophimosis syndrome. All 8 of these children were mentally retarded or developmentally delayed. Two of these 8 had recognized disorders (branchio-oto-renal syndrome and a ring 4 chromosome); the remaining 6 had unrecognized malformation syndromes. Based on this information, it is suggested that children with blepharophimosis be evaluated carefully for underlying conditions and that they be observed for developmental disabilities because of the frequent association.

Telomeric fusion and chromosome instability in multiple tissues of a patient with mosaic Ullrich-Turner syndrome.

We describe the cytogenetic evolution of multiple cell lines in the gonadal tissue of a 10-year-old girl with mosaic Ullrich-Turner syndrome (UTS) involving clonal telomeric associations (tas) of the Y chromosome. G-band analysis of all tissues showed at least 2 cell lines; 45, X and 46,X,tas(Y;21)(q12;p13). However, analysis of left gonadal tissue of this patient showed the evolution of 2 additional cell lines, one designated 45,X,tas(Y;21)(q12;p13),-22 and the other 46,X,tas(Y;21)(q12;p13),+tas(Y;14)(q12;p13), -22. Fluorescence in situ hybridization (FISH) analysis of interphase nuclei from uncultured gonadal tissue confirmed the findings of aneuploidy in the left gonadal tissue and extended the findings of aneuploidy to the tissue of the right gonad. The chromosome findings in the gonadal tissue of this patient suggest a preneoplastic karyotype relating to several distinct tumor associations. The clonal evolution of telomeric fusions indicates chromosomes instability and suggests the extra copy of the Y chromosome may have resulted from a fusion-related malsegregation. In addition, the extra Y suggests low-level amplification of a putative gonadoblastoma gene, while the loss of chromosome 22 suggests the loss of heterozygosity for genes on chromosome 22. This case demonstrates the utility of the study of gonadal tissue in 45,X/46XY UTS patients, and provides evidence that clonal telomeric fusions may, in rare cases, be associated with chromosome malsegregation and with the subsequent evolution of unstable karyotypes.

Sub-band deletion of 7q36.3 in a patient with ring chromosome 7: association with holoprosencephaly.

We report on a patient with ring chromosome 7 analyzed by both high-resolution mid-prophase G-banding and fluorescence in situ hybridization (FISH) resolving a subband deletion of 7q36.3 associated with the clinical manifestation of holoprosencephaly (HPE).

The effects of peer ridicule on depression and self-image among adolescent females with Turner syndrome.

PURPOSE: This study attempted to examine the effects of body image, height dissatisfaction, and peer ridicule on depression and self-image among adolescent females with Turner syndrome. METHODS: A prospective, cross-sectional survey examined 59 subjects' responses to standardized measures of depression, self-image, body image, height perception, and teasing. RESULTS: Descriptive statistics found the mean age of subjects to be 14.8 years (range: 13-19). Approximately 30% reported cardiac defects and 17% indicated kidney anomalies. Only five experienced spontaneous menses and 61% indicated they were receiving estrogen replacement therapy. Linear regression analyses examined the effects of body image, height perceptions, and peer ridicule on depression and self-image scores. The first regression analysis found a five-step model to account for 39% of the variance, with peer ridicule of general appearance being the most important variable. The second linear regression (R2 = .3248, P < .0004) also found peer teasing of general appearance to be significantly associated with self-image scores. Discrepancy scores between ideal versus current body shape or height, as well as teasing about these issues, appeared to be unrelated to depression and self-image among our subjects. CONCLUSION: These data suggest that peer ridicule is a domain that requires ongoing assessment by health care providers, as it appears to be an important contributor to mental health problems. Social skill interventions that emphasize strategies to manage teasing, assertively respond to negative statements, and teach effective coping skills are key variables to minimize the emotional discomfort these young women may experience.

Clouston syndrome: an ectodermal dysplasia without significant dental findings.

The ectodermal dysplasias are a heterogeneous group of conditions primarily affecting the hair, teeth, nails, and skin, and are classified according to the tissue(s) affected. The classification categories are: (1) abnormalities of hair, (2) dental defects, (3) abnormalities of nail morphology, and (4) dyshidrosis. Individuals are grouped according to defects present with findings from two or more categories required for diagnosis. As this classification method is based on phenotype, variable expression or small family size may well have an impact on diagnosis. We report a four-generation family with a hair-nail (1-3) dysplasia with nail morphology that is typical of Clouston syndrome. All affected relatives have thick, discolored, hyperconvex nails with onycholysis, varying degrees of hair involvement, and are hidrotic. They lack hyperkeratosis and multiple caries as originally described in Clouston syndrome. We propose that morphologic abnormalities of the teeth may not occur in the phenotype of Clouston syndrome and that it can be considered a hair-nail (1-3) dysplasia.

Health care utilization and perceptions of health among adolescents and adults with Turner syndrome.

We surveyed women aged 12 years and older who are members of the Turner Syndrome Society of the United States in regard to their health history, current health status, and health care utilization practices to identify the range of health problems and health care practices in this group. The mean age at diagnosis was 10.8 years, and an endocrinologist (41%) or pediatrician (35%) was most likely to make the initial diagnosis. Individuals over age 35 years were diagnosed with Turner syndrome and begun on estrogen replacement therapy at a significantly older age than those who were in younger age groups. Seventy-five percent of the respondents had required some type of surgical procedure, and 14% had been hospitalized within the previous year. Ninety-four percent of women rated their overall health as good to excellent, while 6% rated it fair to poor. In the 12-17-year age group, 89% of the young women were either currently taking or had previously taken growth hormone. The prevalence of major depressive symptoms was slightly higher than the general population for adolescents but similar to the general population for adults. For adult respondents, ratings of fair to poor health were significantly associated with increased outpatient visits. Growth hormone use was significantly associated with increased visits in the adolescent population. Based on these data, it appears that the clinical care of individuals with Turner syndrome has improved, but that they continue to have relatively high hospitalization rates and utilization of subspecialty services. Despite these health problems, most respondents demonstrated good adjustment as determined by standardized mental health measures.

Deaths associated with renal agenesis: a population-based study of birth prevalence, case ascertainment, and etiologic heterogeneity.

We report on deaths associated with renal agenesis among 211,704 consecutive births. Sources included birth and death certificates and an active birth defects surveillance system. Medical review and classification of cases were performed for 1985-1990 events. Sixty-one cases of renal agenesis were identified, and review of records was possible for 59 of the 61 cases. Of these 59 cases, 36 (61%) were confirmed, 5 (8%) were questionable, and 18 (31%) were incorrectly coded. The prevalence of confirmed cases is thus estimated at 17/100,000 births (14.2/100,000 births, excluding elective terminations and fetal deaths). Records incorrectly coded were most often those with multicystic dysplasia. Approximately one-third of cases was found by the birth defects surveillance system alone, confirming the utility of this data source for prevalence estimates. Isolated renal agenesis accounted for 44% of confirmed cases; other diagnoses included VATER association (19%), unrecognized multiple malformation syndromes (17%), exstrophy of the cloaca sequence (14%), and chromosome disorders (6%). Based on these data, prevalence rates for ICD code 753.0 and death include overascertainment of cases from erroneous coding of multicystic dysplasia and underascertainment of cases with unilateral renal agenesis associated with other malformations. Population-based ascertainment of cases by active surveillance methods and rigorous diagnostic coding standards are required to improve the accuracy of these rates. Targeted investigations of distinct subclassifications will be necessary to identify specific etiologic factors.

Perinatal lethal conditions: the effect of diagnosis on decision making.

OBJECTIVE: To identify factors influencing pregnancy management decisions following identification of a perinatal lethal condition. METHODS: One hundred thirty pregnancies with perinatal lethal conditions diagnosed before 24 weeks' gestation were examined. Information collected included demographic data, estimated gestational age at presentation, referral indication, nature of the defect, and performance of autopsy. RESULTS: Eighty-seven families elected to abort affected pregnancies and 43 elected to continue. Demographic factors did not influence decision making, nor did gestational age at diagnosis or referral indication. When comparing the diagnosis of one lethal condition with diagnoses of all other lethal conditions, pregnancies with a central nervous system defect or severe urinary tract defect were more often aborted; those with unexplained severe oligohydramnios and twin pregnancies in which at least one twin was affected were more often continued. Autopsy was obtained much more often in pregnancies that were aborted than in those that were continued. CONCLUSION: The type of defect correlates well with the pregnancy management decision. It is important to consider the type of malformation, certainty of the diagnosis, and level of medical understanding when counseling patients after the diagnosis of a lethal fetal defect. Because many patients will continue pregnancies diagnosed with a perinatal lethal condition, the physician should convey understanding and acceptance of a decision not to abort such a pregnancy. The importance of follow-up testing, including autopsy when appropriate, should be stated clearly.

High-resolution cytogenetic characterization of telomeric associations in ring chromosome 19.

High-resolution cytogenetic studies of a normal individual with ring chromosome 19 indicate that, at the late-to-mid prophase level of band resolution, no apparent chromosomal material is missing, and that telomeric fusion/association, not deletion, is the cause of the ring chromosome formation. Sub-band analysis of the telomeric fusion shows thin chromatin filaments between the telomeres of some of the very elongated ring chromosomes, which cannot be resolved by metaphase chromosome analysis. The ring chromosome found in this individual shows evidence of the characteristic instability associated with ring chromosomes, including duplicated segments, double rings, and subsequent loss of the ring resulting in cells with monosomy 19. The lack of phenotypic effect and the unstable ring behavior, unlike previously reported patients with ring 19, support the formation of this ring by telomeric association.