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Biomedical subjects

A M Lachiewicz

Publications and source records attributed to A M Lachiewicz.

At least 19 recordsLinked to original sources
PubMed2001

Longitudinal study of the carrier testing process for fragile X syndrome: perceptions and coping.

This paper reports the results of a longitudinal study of women at-risk to inherit the fragile X mutation. It addresses 1) how upsetting the women perceived their carrier information to be, 2) how serious a problem they perceive fragile X syndrome to be, and 3) descriptions of feelings about the carrier testing process. The study sample consisted of 42 women (20 carriers and 22 noncarriers). There were two measurement times (just prior to carrier testing and after learning actual carrier status). The measures used were a Fragile X Visual Analog Scale and a structured interview. At time 1, being at-risk was reported to be upsetting and fragile X syndrome was perceived to be a serious problem. For the women found to be carriers there was no change from time 1 to time 2 on any of the items. Significant change occurred in the non-carriers. They were significantly less upset at time 2 after receiving the results of their carrier test than at time 1. They also perceived fragile X syndrome to be a more serious problem than they did at time 1 and a more serious problem than the carriers at time 2. Themes found included concerns that carrier status for fragile X syndrome presented a barrier for having healthy biological children and concern for children's and grandchildren's adaptation to their own carrier status. Coping behaviors were activated to manage the emotions related to these concerns. The coping behaviors identified were minimization, acceptance of the possibility of being a carrier, a sense of being able to deal with the outcome of the carrier test, positive comparison, problem solving, and positive interpretation.

Adaptation, Psychological↗
PubMed2000

Carrier testing in fragile X syndrome: effect on self-concept.

The purpose of the study was to explore self-concept in women at risk for inheriting the fragile X mutation. Time 1 measures were obtained prior to carrier testing and Time 2 measures were collected approximately 5 months after learning carrier status. The sample consisted of 42 women from 17 families. Measures included the Tennessee Self-Concept Scale (TSCS), the fragile X Visual Analog Scale (VAS), and a structured interview. The TSCS provided a global measure of self-concept and the fragile X VAS and structured interview provided a contextual measure of self related to carrier status. Results indicated that there were no differences initially between carriers and noncarriers and no change from Time 1 to Time 2 on the TSCS. Analysis of the Time 1 fragile X VAS means for the total sample found a reduction in positive feelings about self. Analysis of the Time 2 fragile X VAS found that noncarriers reported improvement in feelings about self, with no change in feelings about self found in the carriers. Responses from the structured interview indicated that the feelings regarding self in the context of genetic testing are not related to global self-concept, but result from concerns regarding the implications of a positive carrier test for themselves and their families. This information highlights areas related to carrier testing that warrant further investigation and may ultimately result in modifications to the genetic counseling.

Adult↗
PubMed2000

Physical characteristics of young boys with fragile X syndrome: reasons for difficulties in making a diagnosis in young males.

Fragile X syndrome is the leading form of hereditary mental retardation, but the condition is still underdiagnosed in young children. Because of concern that the fragile X phenotype is subtle in young boys and therefore contributes to underdiagnosis of the disorder, we evaluated 73 boys (36 with fragile X and 37 same-age boys who were fragile X negative) using a checklist that we devised to learn which characteristics might be the most useful for alerting professionals to this diagnosis. After a multiple comparisons adjustment, only 4 of 42 characteristics differed significantly in their distributions between the two groups of boys (P < 0.0012), but 10 other items may also have predictive value for fragile X syndrome (P < 0.01). Four additional items occurred in at least 80% of boys with fragile X and may also be helpful for the clinician. Professionals who work with developmentally delayed children should be aware of these 18 clinical characteristics and some of the behavior characteristics commonly seen in boys with fragile X so that they can readily diagnose patients.

Child↗
PubMed1999

Parental attitudes regarding carrier testing in children at risk for fragile X syndrome.

Sixty-five parents of individuals affected by fragile X syndrome who attended the National Fragile X Conference in Portland, Oregon (1996), were asked to complete a survey assessing parental level of concern about carrier testing in children at risk for fragile X syndrome. All subjects completed a 15-item paper and pencil Likert response scale measure that was developed specifically for this study. The items included parental rights and duties, psychological adjustment, adaptation, discrimination, harm, childbearing, and interpersonal relationships. The major concern of the parents was that their children have knowledge of their carrier status prior to becoming sexually active and that their children be able to marry informed of their genetic risk. Mothers were significantly more concerned than fathers about raising their children with the knowledge of their carrier status. A sense of parental right to make the decision regarding carrier testing for children was associated with concerns about (1) behavioral or educational problems, (2) knowledge of carrier status prior to sexual activity or marriage, and (3) adjustment of the children to knowledge of their carrier status. As the sample was drawn from a unique population of parents, the results of this survey should be interpreted with caution. The findings of this study suggest a model of parents providing anticipatory guidance for their children to help them adjust to carrier information and for their children to have this knowledge prior to the possibility of reproduction.

Attitude to Health↗
PubMed1997

Carrier testing in the fragile X syndrome: attitudes and opinions of obligate carriers.

This study surveyed obligate carriers of the fragile X syndrome fra(X) to ascertain opinions and attitudes regarding carrier testing. Female carriers of fra(X) syndrome were recruited during their visits to the Fragile X Clinic at Duke University Medical Center. Twenty-eight obligate carriers completed a 48 question structured interview and a visual analog scale (VAS). Strong trends in the responses were identified. Fra(X) syndrome was viewed as a very serious problem and the risk to offspring high. Subjects reported that prior knowledge of carrier status would have changed their reproductive plans. All felt that relatives should be informed about the inheritance of fra(X) syndrome; the mean age given for preferred age to inform their children of the inheritance of fra(X) syndrome was 12 years, and mean age given for optimal timing of carrier testing was 10 years. The women interviewed indicated that growing up with knowledge of their carrier status would have been preferable to learning this information as adults and they endorsed an aggressive approach to informing and testing their children. Further investigation is warranted to determine the psychological consequences of carrier testing for fra(X) syndrome in order to develop appropriate guidelines for testing and informing individuals at risk for fra(X) syndrome.

Adult↗
PubMed1996

A fragile X male with a broad smear on Southern blot analysis representing 100-500 CGG repeats and no methylation at the EagI site of the FMR-1 gene.

Fragile X DNA studies were carried out on all obligate carriers of a large fragile X family with 10 mentally retarded individuals. One 64-year-old carrier man with an altered FMR-1 allele was not described as being mentally retarded or as having any limitations in function. He was married, raised 8 children, and worked as an auto mechanic. On examination, he had macrocephaly and mild macroorchidism but few of the other typical physical findings of males with fragile X syndrome. His Full Scale IQ is 73, and his Vineland Adaptive Behavior Composite is 73. On the Woodcock-Johnson Psycho-Educational Battery-Revised, he achieved standard scores of 64 in Reading, 55 in Math, and 83 in Knowledge. His DNA findings showed a broad smear on Southern blot analysis of 100-500 CGG repeats and no methylation at the EagI site upstream of the FMR-1 protein coding region. His FMR-1 protein production is 12% of normal. His daughters all have large premutations, with somatic instability in the size of the CGG repeat lengths. They all have evidence of academic underachievement and 2 have physical characteristics frequently described in individuals with fragile X.

Blotting, Southern↗
PubMed1995

Benzoate therapy and carnitine deficiency in non-ketotic hyperglycinemia.

Five patients presenting with non-ketotic hyperglycinemia in the neonatal period were treated with sodium benzoate to normalize plasma glycine levels. This therapy resulted in seizure reduction and a marked increase in wakefulness. Plasma carnitine deficiency was noted in three of four patients tested, and benzoylcarnitine was identified in plasma, urine, and CSF. Treatment with L-carnitine normalized plasma free carnitine. L-carnitine showed a tendency to increase the glycine conjugation of benzoate. An episode of coma and increased seizures in one patient was associated with a toxic level of benzoate, probably due to insufficient mobilization of glycine for conjugation. High dose benzoate therapy improved the quality of life of surviving patients. Close monitoring of glycine, benzoate and carnitine levels is advised.

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Fragile X phenotype in a patient with a large de novo deletion in Xq27-q28.

A 2-year-old boy with manifestations of the fragile X syndrome was found to have a cytogenetically visible deletion of Xq27-q28 including deletion of FMR-1. Molecular analysis of the patient was recently described in Tarleton et al. [1993: Hum Mol Genet 2(11): 1973-1974] and the deletion was estimated to be at least 3 megabases (Mb). His mother had 2 FMR-1 alleles with normal numbers of CGG repeats, 20 and 32, respectively. Thus, the deletion occurred as a de novo event. The patient does not appear to have clinical or laboratory findings other than those typically associated with fragile X syndrome, suggesting that the deletion does not remove other contiguous genes. This report describes the phenotype of the patient, including psychological studies.

Chromosome Fragility↗
PubMed1994

Behavior problems of young girls with fragile X syndrome: factor scores on the Conners' Parent's Questionnaire.

Mothers of 60 girls with fragile X [fra(X)] and 58 controls were asked to fill out the Conners' Parent's Questionnaire to determine if this commonly used checklist would detect behavior problems in young girls with fra(X). The mean T-scores were significantly different between the 2 groups of girls on 5 of the 6 factors on the Conners' Parent's Questionnaire and the girls with fra(X) had mean T-scores that were above the average range on both the Anxiety factor and the Hyperactivity Index factor. Significantly more girls had T-scores greater than 70 (> 98th centile) on 3 of the 6 factors. Twenty-three percent of the girls had T-scores greater than 70 on the Anxiety factor and 38% of the girls had T-scores greater than 70 on the Hyperactivity Index factor. This study suggests that some behavior problems will be reported frequently in young girls with fra(X) and should not be difficult for clinicians to detect.

Adolescent↗
PubMed1994

Do young boys with fragile X syndrome have macroorchidism?

OBJECTIVE: Macroorchidism is one of the most well-described clinical characteristics of men with fragile X syndrome, but little information has been available regarding macroorchidism in prepubertal boys with fragile X. The purpose of this study was to learn whether macroorchidism is a characteristic of fragile X syndrome in prepubertal boys. METHODS: Clinical assessments were performed on 73 boys, 2.2 to 10.2 years, in whom fragile X either had been diagnosed or who had been referred for fragile X evaluations because of developmental delays. As part of these assessments, we measured testicular volumes using Prader orchiometer beads to find out if macroorchidism occurs before the onset of puberty. RESULTS: From 2.2 through 7 years, boys with fragile X have significantly larger mean testicular volumes than boys without fragile X, but macroorchidism (> or = 4.0 mL or > or = 2 times normal) only occurred in 1 of 27 boys with fragile X. From 8 to 10 years, all our patients with fragile X had clinically enlarged testicles (> or = 3.75 mL), and 7 of 9 boys with fragile X had macroorchidism (> or = 4.0 mL). The testicular volumes of control subjects were all < or = 3.0 mL. CONCLUSIONS: These findings suggest that macroorchidism occurs in some prepubertal boys with fragile X, but in this series it did not occur until age 6 and usually did not occur until after age 8.

Child↗
PubMed1994

Aberrant behaviors of young boys with fragile X syndrome.

To determine whether aberrant behaviors described in boys with fragile X syndrome distinguish them from other boys with developmental disabilities, we asked the primary caregivers of 55 boys with fragile X and 57 matched controls to complete five behavioral questionnaires. Twenty-one items distinguished the groups. Principal components analysis (PCA) yielded five behavioral clusters: abnormal language, tactile defensiveness, poor self-control, poor eye contact/shyness, and hand flapping. Boys with fragile X were found times more likely to have both tactile defensiveness and abnormal language. The presence of these abnormal behaviors in boys with developmental delays warrants further assessment for fragile X.

Autistic Disorder↗
PubMed1993

Evidence that methylation of the FMR-I locus is responsible for variable phenotypic expression of the fragile X syndrome.

DNA at the FMR-1 locus was analyzed by Southern blot using probe StB12.3 in an unusual fragile X family with six brothers, three of whom are affected with fragile X to varying degrees, two of whom are nonpenetrant carriers, and one of whom is unaffected. Fragile X chromosome studies, detailed physical examinations, and psychological testing were completed on all six. Two of the affected brothers and the two nonpenetrant brothers were found to be methylation mosaics. The three affected males spanned the phenotypic and cognitive spectrum of the fragile X syndrome. A correlation was seen between the degree of methylation and the phenotypic expression identified in the three affected males. The two males initially classified as nonpenetrant were found to have mild phenotypic expression which consisted of minor cognitive deficits and a partial physical phenotype. These two, who were negative on fragile X chromosome studies, were found on DNA analysis to have large broad smears, with approximately 97% of the DNA unmethylated. The results described here indicate that some "nonpenetrant" carrier males may have varying amounts of methylation of the FMR-1 region, which can result in mild expression of the fragile X syndrome. The apparently mild phenotypic and cognitive expression of the fragile X syndrome in the two males, initially classified as nonpenetrant, who are mosaic for hypermethylation of an expansion of the CGG repeat in the premutation range, indicates that expression of the syndrome is not confined to males with large, hypermethylated expansions (full mutation) but has instead a gradient effect with a threshold for the full expression of the phenotype.

Adult↗
PubMed1991

Association of the Robin sequence with the fragile X syndrome.

We report on 4 individuals with the fragile X [fra(X)] syndrome and the Robin sequence (or elements of that sequence). To our knowledge, this association has been described in only one other boy. However, males with the fra(X) syndrome have been reported to have an increased incidence of cleft palate. We recommend that children with a cleft palate or the Robin sequence be assessed for developmental delays and a family history of mental retardation. The fra(X) syndrome may be one of the genetic causes of the Robin sequence and, when indicated, children with the sequence should be tested for fra(X).

Cleft Palate↗
PubMed1991

Townes-Brocks syndrome in two mentally retarded youngsters.

We report on 2 children with Townes-Brocks syndrome (TBS) and mental retardation. One child had mild hearing loss, but the other only had hearing loss at 8000 Hz. These cases suggest that there may be an increased incidence of mental retardation in individuals with TBS.

Abnormalities, Multiple↗
PubMed1990

Developmental implications of changing trajectories of IQ in males with fragile X syndrome.

This study examined the trajectories of cognitive development in boys under the age of 21 years with fragile X syndrome. By combining information from three centers, data from 66 boys were analyzed; only children who had been tested two or more times with the same psychometric instrument at one or more year intervals were included in this study. Results demonstrated that males with fragile X syndrome show a decline in IQ scores, with the most marked declines seen during the early pubertal period. All 22 children retested during the 11- to 15-year period showed IQ declines, suggesting a slowing of development associated with the onset of puberty. Before age 10 years, males with higher (as opposed to lower) pretest IQs were more likely to decline at subsequent testings. A single etiological factor may not be sufficient to account for the observed findings, as both changes in neurobiological- and task-related factors seem implicated in the slowing intellectual development of this population.

Adolescent↗
PubMed1987

Declining IQs of young males with the fragile X syndrome.

Retrospective, longitudinal data were obtained on 21 boys with the fragile X syndrome to assess whether their IQs declined during childhood. For the group as a whole, IQs dropped significantly; 13 boys showed a significant decline at retest. Our results are consistent with reports that young boys with the fragile X syndrome may be only mildly impaired, whereas adults with this syndrome are usually moderately or severely retarded. Parents of young boys with the fragile X syndrome should be cautioned that the IQ of their child may decline.

Adolescent↗