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Biomedical subjects

Jane A Evans

Publications and source records attributed to Jane A Evans.

15 recordsLinked to original sources
PubMed2007

Triphalangeal thumb in association with split hand/foot: a phenotypic marker for SHFM3?

BACKGROUND: At least five distinct loci have been implicated in split hand foot malformation (SHFM). Establishing genotype/phenotype correlations at the chromosomal level may elucidate responsible developmental genes and improve patient management. In our analysis of previously published genetically mapped SHFM cases, preaxial hand involvement was a significant discriminating variable, most commonly seen at the SHFM3 locus (OMIM 600095) at 10q24. Of the 47 SHFM3 patients analyzed, 15 (31.9%) had triphalangeal thumb (TPT), a limb finding not reported at any other locus. METHODS: The association of TPT/split foot, in particular, prompted us to review the literature for similar cases. RESULTS: We ascertained a number of unmapped familial and sporadic cases with TPT/split foot, including a group of patients with triphalangeal thumb-brachyectrodactyly syndrome. Certain trends were similar in both SHFM3 and these unmapped literature cases. With respect to gender, 7/12 (58%) of mapped SHFM3 cases with TPT/split foot were male whereas 5/12 (42%) were female, compared with 22/50 (44%) males and 28/50 (56%) females among unmapped cases (P=0.3715). Individuals in both groups usually had bilateral involvement, with 67 and 60% showing bilateral TPT among mapped and literature cases, respectively (P=0.6714). Bilateral involvement of the feet was even more striking (83% of SHFM3 patients and 96% of literature cases; P=0.0808). CONCLUSIONS: Patients with TPT/split foot may in fact represent SHFM3 cases and should be evaluated for genomic rearrangements at 10q24. TPT may be identified only by radiographic analysis, emphasizing the importance of imaging these patients and their family members.

F-Box Proteins↗
PubMed2006

Maternal serum alpha-fetoprotein levels in fetal hydrocephalus: a retrospective population based study.

BACKGROUND: Although maternal serum alpha-fetoprotein (MSAFP) is a highly sensitive marker for certain congenital malformations such as open neural tube and ventral wall defects, its usefulness as a screening test for fetal hydrocephalus is uncertain. We wished to determine the distribution of maternal serum alpha-fetoprotein levels associated with fetal hydrocephalus in a population-based screening program in Manitoba, and their potential relationship to additional anomalies. METHODS: Cases of fetal hydrocephalus unrelated to neural tube defects were ascertained from multiple sources and reviewed. Cross-reference with the Manitoba Maternal Serum Screening Program database determined which mothers had undergone maternal serum screening. Mean MSAFP levels in both isolated and complex hydrocephalus were calculated and compared with the general population of screened pregnancies using Independent Samples T-tests. RESULTS: Mean MSAFP levels in 70 cases of fetal hydrocephalus were significantly higher than those of the general population of screened pregnancies (P = 0.029). This was due to the fact that mean MSAFP levels in those cases with other major anomalies were increased over those of the general population (P = 0.041); cases with hydrocephalus alone showed no significant difference (P = 0.203). Only seven cases (10%) had MSAFP levels > or = 2.3 multiples of the median, the cut-off used in Manitoba. However, six of these (86%) had additional major and/or minor malformations. CONCLUSION: MSAFP screening has low sensitivity for fetal hydrocephalus and is rarely elevated in isolated cases. However, when fetal hydrocephalus is detected, elevated MSAFP levels indicate that the fetus is at significant risk to have additional malformations and further investigations, including chromosome breakage studies, may be indicated.

Journal Article↗
PubMed2006

Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients.

Split hand foot malformation (SHFM) also known as central ray deficiency, ectrodactyly and cleft hand/foot, is one of the most complex of limb malformations. SHFM can occur as an isolated malformation or in association with other malformations, as in the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and other autosomal dominant conditions with long bone involvement, all showing variable expressivity and reduced penetrance. The deficiency in SHFM patients can also be accompanied by other distal limb anomalies including polydactyly and/or syndactyly. This variability causes the phenotypic classification of SHFM to be far from straightforward and genetic heterogeneity, with at least five loci identified to date, further complicates management of affected patients and their families. Although genotypic-phenotypic correlations have been proposed at the molecular level for SHFM4 patients who have mutations in the P63 gene, phenotypic correlations at the chromosomal level have not been thoroughly documented. Using descriptive epidemiology, Chi square and discriminant function analyses, our laboratory has identified phenotypic patterns associated with the mapped genetic SHFM loci. These findings can assist in classification, provide insight into responsible developmental genes and assist in directing mapping efforts and targeted genetic testing, resulting in more accurate information for family members in the clinical setting. Comparison with relevant animal models is discussed.

Abnormalities, Multiple↗
PubMed2006

Clinical and epidemiological findings in patients with central ray deficiency: split hand foot malformation (SHFM) in Manitoba, Canada.

We conducted a clinical population study to examine the incidence and epidemiology of split hand foot-malformation (SHFM) in Manitoba from 1957 to 2003. The total number of births during this period was 850,742. Forty-three patients with SHFM were identified, resulting in an incidence of 1 in 19,784 births. Most patients were ascertained through referrals to the Section of Genetics and Metabolism at the Children's Hospital, Winnipeg, Manitoba. Overall, 22 (51.2%) of affected individuals were females and 21 (48.8%) were male. The left upper limb (LUL) was the most frequently affected, (in 46.5% of patients). The right hand was involved in 39.5%. In 4 patients (9.3%) all four limbs were affected. SHFM is classified as a failure of formation of parts according to the International Federation of Surgical Societies of the Hand (IFSSH) and has also been categorized as Typical or Atypical. Individuals in the Manitoba cohort were classified into two main categories: Typical (29 cases) and Atypical (3 cases). However, 11 patients were not easily placed into either group and comprised a distinct category termed "difficult to classify." Patients in the three groups were then further subdivided depending on whether or not they had additional congenital anomalies. These complex patients included those with single gene disorders in which SHFM has been reported (e.g., ectodermal dysplasia Ectrodactyly Clefting (EEC), tibial aplasia with SHFM, fibular aplasia with SHFM), as well as those with other recognized or unknown patterns of anomalies. Two had deletions involving 9q and 5p respectively. Unlike some other studies, we did not find an excess of males or right-sided defects and only two of the cases--two sisters--were related.

Cohort Studies↗
PubMed2005

Continuity or colonization in Anglo-Saxon England? Isotope evidence for mobility, subsistence practice, and status at West Heslerton.

The adventus Saxonum is a crucial event in English protohistory. Scholars from a range of disciplines dispute the scale and demographic profile of the purported colonizing population. The 5th-7th century burial ground at West Heslerton, North Yorkshire, is one of the few Anglian cemeteries where an associated settlement site has been identified and subjected to extensive multidisciplinary postexcavation study. Skeletal and grave good evidence has been used to indicate the presence of Scandinavian settlers. A small, preliminary study using lead and strontium isotope analysis of tooth enamel, mineralized in early childhood, from Neolithic/Early Bronze Age (n = 8), Iron Age (n = 2), and Early Anglo-Saxon (n = 32) skeletons, was carried out to directly investigate this hypothesis. Results suggest that lead provides dissimilar types of information in different time periods. In post-Roman England, it appears to reflect the level of exposure to circulated anthropogenic rather than natural geological lead, thus being a cultural rather than geographical marker. Consequently, only strontium provides mobility evidence among the Anglian population, whereas both isotope systems do so in pre-Roman periods. Strontium data imply the presence of two groups: one of "local" and one of "nonlocal" origin, but more work is required to define the limits of local variation and identify immigrants with confidence. Correlations with traditional archaeological evidence are inconclusive. While the majority of juveniles and prehistoric individuals fall within the "local" group, both groups contain juveniles, and adults of both sexes. There is thus no clear support for the exclusively male, military-elite invasion model at this site.

Dental Enamel↗
PubMed2004

The C677T methylenetetrahydrofolate reductase variant and third trimester obstetrical complications in women with unexplained elevations of maternal serum alpha-fetoprotein.

INTRODUCTION: The C677T MTHFR variant has been associated with the same third trimester pregnancy complications as seen in women who have elevations of maternal serum alpha-fetoprotein (MSAFP). We hypothesized that these women with third trimester pregnancy complications and MSAFP elevations would have an increased frequency of the variant compared to an abnormal study control group (women with MSAFP elevations without pregnancy complications) as well as to normal population controls. METHODS: Women who had unexplained elevations of MSAFP in pregnancy were ascertained retrospectively. The frequency of the C677T MTHFR variant among those women with unexplained elevations of MSAFP who had experienced later pregnancy complications was compared to that of women with unexplained elevations of MSAFP without complications as well as to that of the previously established Manitoba frequency. RESULTS: Women who had complications of pregnancy and an unexplained MSAFP elevation had a higher allele frequency for the C677T MTHFR variant (q = 0.36,) compared to women with MSAFP elevations and normal pregnancy outcomes (q = 0.25, OR 1.73 95% CI 1.25-2.37, p = 0.03). The frequency was also higher than that of the population controls (q= 0.25, OR 1.70 95% CI 1.11-2.60, p = 0.007). The frequency in women with MSAFP elevations without pregnancy complications was not significantly different from that of the population controls (p = 0.41). CONCLUSION: Women with unexplained elevations of MSAFP and who experience complications in later pregnancy are more likely to have one or two alleles of the C677T MTHFR variant.

Cytosine↗
PubMed2004

The duplicated longitudinal epiphysis or "kissing delta phalanx": evolution and variation in three different disorders.

BACKGROUND: The delta phalanx, also known as the delta bone, or longitudinal epiphyseal bracket (LEB), has been described in a variety of syndromes and dysplasias. However, the "kissing delta phalanx" is not as well recognized in the literature; it consists of a duplicated longitudinal bracketed epiphysis, or a complex of two adjacent delta bones, with opposing convex portions facing each other. Magnetic resonance imaging of the kissing delta phalanx has not been previously described. OBJECTIVE: To describe the evolution, variation and associated osseous anomalies of the kissing delta phalanx in three patients with distinct distal limb malformations using both plain films and magnetic resonance imaging. RESULTS: Patient 1 had Rubinstein-Taybi syndrome and, in addition to a kissing delta phalanx in both feet, had corresponding delta metatarsals (MT1). Patient 2 had Cenani-Lenz syndactyly with distinct variation of the kissing delta phalanx in each hand. He had a disorganized appearance to the phalanges, metacarpal fusions and carpal coalitions. Patient 3 had an isolated oligosyndactyly of the left hand with metacarpal fusions and carpal coalitions. All three patients were followed over time. We describe two types of kissing delta phalanges: separated (without fusion of the corresponding epiphyseal brackets) and nonseparated (with fusion of the corresponding epiphyseal brackets). Both types can be seen in the same patient and are a reflection of the relative degree of segmentation of the two delta bones. CONCLUSION: The appearance of this rare osseous abnormality changes with time and can be found in a limited number of uncommon disorders. It can also be found in association with other osseous anomalies of the distal extremities; therefore magnetic resonance imaging early in life can greatly assist in surgical planning. Recognition of the kissing delta phalanx may be an important radiological clue to diagnosis of these rare disorders.

Child, Preschool↗
PubMed2004

Cenani-Lenz syndactyly in a patient with features of Kabuki syndrome.

We report a 5 9/12-year-old male with Cenani-Lenz syndactyly (CLS). He presented with three malformed digits on each hand and bilateral 2,3 partial cutaneous toe syndactyly. The expression of this presumed autosomal recessive disorder is variable and has been confused with split hand foot malformation (SHFM). Not all CLS patients show the typical 'spoon hand' configuration originally described. Affected CLS patients show a disorganized appearance of the phalanges with some degree of syndactyly/oligodactyly, in addition to metacarpal and carpal fusions. Radioulnar synostosis may be present. Cases lacking radioulnar synostosis may show proximal dislocation of the radial heads. The distal limb anomalies seen in our patient resemble other reported CLS patients. Radiographic evaluation showed a disorganized appearance of the phalanges, a 'kissing delta phalanx' of one proximal phalanx, metacarpal fusions, carpal coalitions and posterior subluxation of the radial heads. Clinical examination revealed features suggestive of Kabuki syndrome including large, prominent ears, sparse, medially flared and arched eyebrows, wide palpebral fissures, long eyelashes, and oligodontia with flat head 'screwdriver-shaped' incisors, in addition to persistent finger and thumb-tip pads. The faces of CLS patients are rarely shown or described. However, some patients in published reports have large, prominent ears. A recent report suggested midfacial dysmorphism in two patients with CLS (). Although the findings of CLS with features of Kabuki syndrome in our patient may be coincidental, the faces of CLS patients need to be carefully evaluated and described to determine if there is a distinctive accompanying facial phenotype.

Bone and Bones↗
PubMed2003

Rib defects in patterns of multiple malformations: a retrospective review and phenotypic analysis of 47 cases.

Rib anomalies may occur in isolation, as well as in association with abnormalities of vertebral segmentation and multi-system malformations. Specific entities include the VACTERL and MURCS associations, spondylocostal dysostosis, and spondylothoracic dysostosis. The relative significance of rib anomalies in other lesser known syndromes and associations remains unclear. To document the diagnoses and related defects in patients with rib anomalies as part of broader pattern of anomalies, we retrospectively identified 47 cases from a hospital population, and evaluated specific costal findings and associated birth defects. In our study, fusion was the most common pattern of rib anomaly (72%), followed by bifid (28%) and hypoplastic ribs (26%). Unrecognized patterns of multiple congenital anomalies (MCA) and VACTERL association were the commonest specific diagnoses with a frequency of 30 and 28%, respectively. An associated vertebral defect was found in 72% of the patients. Of those with no vertebral anomaly, the combinations of "rib and cardiac defects alone" and "rib and renal defects alone" were seen in one-third of the patients (4/13). Both the occurrence and type of rib anomaly were helpful in defining certain syndromes and enhanced the likelihood of identifying related malformations.

Abnormalities, Multiple↗
PubMed2003

Humeroradial synostosis, ulnar aplasia and oligodactyly, with contralateral amelia, in a child with prenatal cocaine exposure.

Humeral "bifurcation" due to humeroradial synostosis, and amelia are both very rare limb anomalies. We report on a Canadian. Aboriginal boy with both these limb deficiencies. The family history was unremarkable, but he was exposed prenatally to cocaine at the time of limb development. Humeroradial synostosis with ulnar aplasia has been reported by several authors. The majority of cases are unilateral. When both upper limbs arms are involved, cases with oligodactyly often have asymmetrical limb deficiencies and have all been sporadic to date. Some appear to represent cases of the femur-fibula-ulna or FFU complex. Affected individuals with normal hands usually have symmetrical defects and show an autosomal recessive pattern of inheritance. Limb deficiencies have been reported in several infants exposed prenatally to cocaine and have been inducible in animal models. Most are terminal transverse defects or deficiencies of middle digits. When more than one limb is involved, the defects are usually asymmetric. Our case appears to be one of the most severely affected children reported to date.

Abnormalities, Drug-Induced↗
PubMed2002

Fibular aplasia with ectrodactyly.

Fibular aplasia with split hand/foot or other defects of the central axis is a rare disorder that shares several characteristics with the better known tibial aplasia-ectrodactyly syndrome. They appear to be inherited in an autosomal dominant fashion. In both, however, the phenotype is markedly variable, penetrance is reduced, and apparently sporadic cases are relatively frequent. We report a new case of this disorder and review the clinical and demographic findings in 47 others identified from the literature or other sources. A key observation was that the sex ratio is biased toward males, especially in apparently sporadic cases. This male bias is largely explained by a lower penetrance rate in women. Both affected males and females had affected children, but the risk to offspring was higher when the mother carried the gene, in keeping with a mixed model for genetic susceptibility, i.e., the penetrance of the major predisposing gene is acting against a multifactorially determined level of liability. Given the high degree of nonpenetrance and very variable expressivity, counseling with respect to recurrence risk is problematic and will likely remain so, even when the major predisposing gene is identified.

Abnormalities, Multiple↗
PubMed2002

Very low second-trimester maternal serum alpha-fetoprotein: Association with high birth weight.

OBJECTIVE: To investigate the relationship between very low maternal serum alpha-fetoprotein levels (MSAFP), neonatal size, and possible associations with obstetric complications. METHODS: This is a retrospective case-control study in a population managed prospectively by a standardized protocol. Perinatal outcomes were compared between patients with unexplained very low MSAFP (less than or equal to 0.25 multiples of the median) and control pregnancies with normal MSAFP, matched by precise gestational age, parity, maternal age within 1 year, and gender of the newborn. RESULTS: Of the 84,909 women screened, 464 (0.55%) met the definition of very low MSAFP. On tertiary evaluation, 226 had dates reassigned by ultrasound. After exclusion of overt diabetics, patients who were not pregnant, invalidated MSAFP, and 17 patients lost to follow-up, 178 women (0.21% of the total) had true very low MSAFP. True very low MSAFP was associated with subsequent miscarriage in 67 women and with fetal aneuploidy and/or serious abnormalities in 12 patients, leaving a population of 97 women (1.14 per 1000 women screened) with unexplained very low MSAFP. Without obvious demographic or obstetric factors, these women had heavier babies, more babies above the 90th percentile, more delivery complications caused by large birth weight (41 versus 16, chi(2), P <.001) compared with gestational-age matched controls from the same screened population who had normal MSAFP. CONCLUSION: Very low MSAFP predicts an unusually high rate of large birth weight infants, with increased fetal, intrapartum, and neonatal consequences. Maternal medical conditions or obvious demographic factors do not explain these consequences. These findings suggest a role for close fetal surveillance in the third trimester and extended efforts to assess maternal and neonatal glucose status.

Adult↗
PubMed2002

Tibial agenesis with radial ray and cardiovascular defects.

The combination of tibial agenesis with radial ray and cardiovascular defects has been observed in patients with Mendelian disorders and in those with multiple congenital anomalies of unknown cause. We report two apparently unrelated children who had unusual combinations of such findings in association with other, predominantly midline, anomalies (imperforate anus, extra ribs, uterus didelphys). Comparison of the anomalies in these infants and similar cases from the literature suggests that they may represent examples of an association of the cardiogenic and limb developmental fields occurring either as manifestations of a previously unrecognized single gene disorder or as an expansion of the VACTERL association.

Abnormalities, Multiple↗