Jane A. Evans

A cytogenetic survey of 14,069 newborn infants

Between 1970 and 1973, 14,069 consecutive liveborn infants at the Womens Centre, Winnipeg, were subjected to karyotypic analysis. The details of the materials and methods and the preliminary findings of the study have been previously published [1,2]. A total of 15 nonmosaic and 4 mosaic infants with sex chromosome anomalies were detected: 12 males and 7 females. These children have been followed wherever possible by physical and developmental evaluations, and preliminary findings have been reported previously [3]. In order to obtain further baseline data on these children while they were still prepubertal, it was decided to recontact all families and encourage them to present their children for further physical evaluation and psychologic testing. Details of these investigations and their results are given in this paper.A study of the chromosomes of 14,069 consecutive liveborn infants revealed 11 infants with balanced reciprocal and 13 with balanced Robertsonian translocations. A detailed physical assessment revealed

CCMG statement on direct-to-consumer genetic testing.

This statement was developed by the Canadian College of Medical Geneticists (CCMG) Ethics and Public Policy committee with input from members of the Molecular Genetics and Clinical Practice committees and the membership-at-large. This statement has been approved by the CCMG Board of Directors. The statement should be viewed as a living document, as it reflects current knowledge and experience which will change over time.

Tracheal agenesis revisited: analysis of associated anomalies

We describe five new cases of tracheal agenesis and report on epidemiological and numerical analyses of nearly 100 such cases with multiple congenital anomalies. Malformations seen with tracheal agenesis form patterns which overlap with, but are distinct from, VACTERL association. They have a high frequency of other lower respiratory tract anomalies; e.g., laryngeal atresia and lung lobation defects, and complex heart anomalies, but fewer anal and vertebral malformations. Cluster analysis of the malformations in 86 patients identified four consistent groups. Anomalies in the first group were primarily restricted to the trachea, larynx, and cardiovascular system. In the second group, the patients had more severe cardiac defects, and lung lobation anomalies, while in the third they had a caudal component in addition to thoracic abnormalities, with anal and renal anomalies being common. Each of these groups showed a male excess and may represent increasingly severe perturbations in development fields encompassing the developing respiratory tract. Although the nature of the causative insult is unknown and probably heterogenous, one underlying pathogenetic mechanism may be abnormal epithelial-mesenchymal interactions. Patients in the fourth group also had multisystem involvement with a high incidence of aberrant vessels, complex cardiac malformations, lung lobation defects, and anomalies of other foregut derivatives. The sex ratio in this group was normal and such cases could represent a disturbance in the primary development field during blastogenesis with secondary vascular disruptions. Complete tracheal agenesis is a lethal anomaly. However, segmental forms may be correctable and, in this group of infants, the nature of associated anomalies may well determine long-term prognosis.

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.

Spina bifida before and after folic acid fortification in Canada.

BACKGROUND In 1998, fortification of a large variety of cereal products with folic acid became mandatory in Canada. A multicentric study was carried out to assess the impact of this policy on the frequency of NTDs. The present analysis focused on spina bifida. METHODS The study population included approximately 2 million livebirths, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces, from 1993 to 2002. Spina bifida cases were divided according to the upper limit of the defect: upper (cranial, cervical, or thoracic) and lower (lumbar or sacral) defects. Based on published results of red blood cell folate tests, the study period was divided into prefortification, partial fortification, and full fortification periods. RESULTS A total of 1,286 spina bifida cases were identified: 51% livebirths, 3% stillbirths, and 46% terminations. Prevalence decreased from 0.86/1,000 in the prefortification to 0.40 in the full fortification period, while the proportion of upper defects decreased from 32% to 13%. Following fortification, regional variations in the prevalence and distribution of sites almost disappeared. CONCLUSIONS Results confirmed the etiologic heterogeneity of spina bifida and the more pronounced effect of folic acid in decreasing the risk of the more severe clinical presentations.

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.A patient who had a karyotype 46,XY, del (10) (q11q21) is reported. The clinical findings in this boy included significant development delay and what appeared to be a combination of positional deformities and minor anomalies.

Agenesis of the penis: Patterns of associated malformations

Agenesis of the penis is a rare malformation that occurs in otherwise normal males or together with other anomalies. In this article, we document unusual patterns of malformations in four such infants and analyze the nature and incidence of defects in 57 cases by clinical evaluation and numerical classification techniques. Although patients with this condition previously have been divided into groups based on the position of the urethral meatus in relation to the anus (presphincteric, postsphincteric, urethral atresia), our analyses suggest that most cases can be classified into either a severe form (16%) with renal aplasia or dysplasia and other caudal anomalies or a second group (72%) with low mortality and fewer additional malformations. The remaining cases in our group represented unique patterns stemming from a variety of causes, including etretinate embryopathy and the human homologue of the disorganization mutation. Agenesis of the penis occurs as a consequence of single gene disorders, teratogenic effects, or malformation sequences and associations and in unrecognized patterns of anomalies. It thus should be considered a developmental field defect. Its concurrence with scrotal hypoplasia, absent raphe, and anal anomalies implies a major disturbance of the caudal mesoderm. In such cases, severe renal defects are usually seen, and the prognosis is poor. When the patient has a patent urethra and normal scrotum, raphe, and testes, however, penile agenesis may be a localized malformation of the genital tubercle potentially related to penoscrotal transposition, a phylogenetic anomaly that is the normal genital arrangement in male marsupials, rabbits, and certain other mammals. Infants with isolated penile agenesis have generally done well. In the past, many were not treated; however, current recommendations are to use appropriate surgical and endocrine techniques to reassign female gender and enhance sexual and psychosocial functioning, though this approach is the subject of controversy.

The Coffin‐Lowry syndrome. Experience from four centres

The Coffin‐Lowry syndrome is an established syndrome of mental retardation, a characteristic facies and skeletal anomalies. This paper describes 12 cases from eight families and compares their findings with those of previously reported patients. The differential diagnosis is considered. Physical findings and pedigree data strongly support X‐linked semi‐dominant inheritance. The gene appears widely distributed and, as expected, a significant proportion of cases represent new mutations. We cannot confirm the metacarpal‐phalangeal profile or fingertip dermatoglyphics as useful diagnostic aids. Skin biopsy studies from four of our patients gave no evidence for a primary disorder of lysosomes or a degenerative disease. Caution is urged before assuming that such patients will all show intellectual deterioration.

Split Hand Foot Malformation (SHFM)

The nomenclature describing the phenotype of missing central rays in the hand and/or foot in the genetics and surgical literature is heterogeneous and confusing. Split hand/foot malformation (SHFM) is the most common term for this phenotype in the genetics community; however, other names such as the offensive ‘lobster‐claw malformation’ and the non‐specific ‘ectrodactyly’ are still utilized to describe this malformation. In this article, we briefly review the nomenclature associated with SHFM and its classifications.

Down syndrome and recent demographic trends in Manitoba.

Two hundred and thirty-three children born in Manitoba with Down syndrome between 1965 and 1974 were ascertained and the maternal ages obtained. Mean maternal age was found to have declined in this period both for all livebirths and to a greater extent for Down syndrome children. Though the proportion of mothers of Down syndrome infants with a maternal age of less than 35 years remained the same, the proportion of mothers aged 35 to 39 years increased and the age specific incidence of Down syndrome became significantly greater for women in this age group. Reduction in the proportion of Down syndrome births to women over 40 years and the increased incidence of Down syndrome in children of women aged 35 to 39 years has important consequences for the planning of amniocentesis programmes.