Biomedical subjects
Publications and source records attributed to M Le Merrer.
We report two sibships with children who had anophthalmia, multiple limb abnormalities, and consanguineous parents. The same association of malformations has already been reported. These further observations allow a better delineation of the syndrome and confirm its autosomal recessive mode of inheritance. We propose to name the syndrome ophthalmo-acromelic.
Result of a family study based on 584 patients with craniostenosis brings some answers useful for genetic counselling. For 98 patients (15%) a syndrome is associated. Third part of them has Apert syndrome, an other third part has Crouzon syndrome, and for the last third more exceptional acrocephalosyndactyly syndrome (Saethre-Chotzen, Pfeiffer) or others atypical associations, sometimes not yet described, but with an autosomal dominant inheritance. Non syndromic craniostenosis involves differently according to the type of join, but the localization is the same if recurrence will be happen. Coronal craniostenosis seems to be a dominant autosomal character, when scaphocephaly is more often sporadic; for both, an autosomal dominant inheritance is not excluded for some pedigrees. If the recurrence risk exist in some cases, it is generally well accepted by parents on account of the good neurosurgeon prognosis.
We report two children with a common pattern of birth defects. Both have very sparse, curly hair, nystagmus and mental retardation. The first one has Noonan syndrome habitus associated with keratosis plantaris and nystagmus; the second one has a slightly Noonan-like face, macrocephaly, keratosis pilaris, and hypertrophic cardiomyopathy. They represent the extreme of a spectrum of congenital defects recently reported independently as CFC syndrome by Reynolds and as "Noonan-like short stature syndrome with sparse hair" by Baraitser and Patton. The clinical features are reviewed and the autonomy of the syndrome with regards to Noonan syndrome, is disputed, since every sign seems to occur independently in Noonan syndrome. The father of the second case probably has a minor syndrome expression, pointing to probable autosomal dominant inheritance.
We report a family in which Opitz-Frias G syndrome is expressed across 4 generations. The propositus displays hypertelorism, low grade hypospadias, cleft palate and lips and cleft larynx, making the diagnosis of G syndrome very likely. A cousin of his mother discloses similar clefts, vulviform hypospadias, anal imperforation and mental retardation. His clinical appearance fits perfectly the diagnosis of BBB syndrome. A nephew shows ambiguous genitalia and hypertelorism. Authors suggest the lumping of the BBB and the G syndrome.
The authors report three cases of a new syndrome which characteristic anomalies are facial dysmorphism with anteverted nose, down slanting palpebral fissures, ptosis, severe microretrognatia, polydactyly. The authors insist on the particular severe genital anomalies, the failure to thrive and the constant lethal issue. The authors discuss the diagnosis of Smith-Lemli-Opitz syndrome and suggest the possibility of a new entity always confounded with others associations characterized by a polydactyly and a sexual reversion in male.
The embryonic testicular regression syndrome associated with severe mental retardation is reported in three 46,XY sibs each of whom has a 46,XY chromosome complement. A fourth sib, a sister, also is severely retarded mentally; her chromosome complement is 46,XX. The 46,XY individuals, who were raised as females, presented varying degrees of genital ambiguity, indicating that their gonadal activities had been arrested at different times during embryogenesis. No trace of gonadal tissue could be found in either patient. The coincidence of the embryonic testicular regression syndrome and severe mental retardation in the same sibship is discussed.
34.2% of couples seen during the years 1982 and 1983 for genetic counselling had some kind of familial anamnesis such as affected partner or relative or children. They could have benefit from prenatal diagnosis who would have been accurate informative twice on three times. Indications methods and accuracy are studied in consideration to the reason of referring and the level of the risk. Genetic counselling and prenatal diagnosis appear as preventive means adapted to each consultant. Otherwise systematic ultrasonography allows a true prevention from which 17.6% of the couples having give birth to affected children could have benefit.
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We report the prenatal diagnosis in a 20 week male fetus at risk of chronic granulomatous disease (CGD). A previous affected brother was known in the family and the mother was detected as heterozygote. Three different assays were performed on fetal blood obtained under fetoscopy: cytochemical reduction of nitroblue tetrazolium (NBT), chemiluminescence after activation by opsonized zymosan or phorbol myristate acetate (PMA) and production of superoxide anion (O2-.). Results were comparable to those obtained in 6 fetuses investigated for other inherited diseases. Absence of functional polymorphonuclear defects was confirmed at birth. The use of 3 different techniques performed on whole blood for prenatal diagnosis of CGD has to be recommended instead of an isolated technique adapted to whole blood tests.
From their personal experience, the authors demonstrate that, in spite of increased requests in general, couples in underprivileged socio-cultural classes are insufficiently concerned by genetic counselling; on the contrary it is too often requested by women who are already pregnant. They emphasize the necessity of providing information to all at risk couples and the essential part taken by family doctors. They discuss the difficulties of geneticists when consulters do not express a real question or wait to be given a rule of behaviour. Antenatal diagnosis (proposed to 2 of every 5 couples in 1983) changed the concept of genetic counselling by replacing a probability (the risk) by a certainty (the child presents with the disease or is normal). However, one should not look to either genetic counselling or antenatal diagnosis for a considerable decrease in the incidence of affected children.
The authors from two independent patterns, genetic counselling on the one hand, familial study on the other hand show that the procreation rate of parents with affected children with spina bifida, digestive malformations and autosomal recessive diseases depend especially on the motherhood eagerness, on the mothers' age, on the family composition and on the possibilities of prenatal diagnosis effort to severely suffered parents before.
A familial study was undertaken on 382 probands with transposition of the great vessels, 348 with coarctation of the aorta and 143 with hypoplastic left heart syndrome. It allowed to assess in sibs the frequency of identical congenital heart diseases (respectively 0.15, 0.42 and 3.41%) and of all 7.32%). The epidemiological study did not provide further data worth noting. At the origin of the transposition of the great vessels, tetratogenetic factors are added to genetic factors, whose part is of little importance; hypoplastic left heart syndromes are heterogeneous (recessive autosomal transmission, chromosome abnormalities, sporadic cases). Coarctations of the aorta, which are dependent on different mechanisms are also heterogeneous. It is possible that common factors, whether hereditary or not, play a part on one hand in hypoplastic left heart syndromes and coarctations of the aorta, and, on the other hand, in some congenital heart diseases.
The purpose of this report is to describe a familial observation of EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft palate). The two cases, a boy and his mother, had no cleft palate but the teeth malformations were typical of this affection. The variability of the syndrome is discussed.
The authors, from their experience emphasize the associated malformations' frequency in major congenital urinary tract malformations (26,9%). It is essential to recognize in these multiple defects some certified syndromes - inherited or not. The most associations are still unknown, nevertheless the genetic counselling require an accurate diagnosis.
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Segregation analysis was performed on a subset of a large body of French data comprising 298 nuclear families. Two models were used in this analysis: the transmission probability model [Elston and Stewart, 1971; Elston, 1981] and the mixed model [Morton and MacLean, 1974]. Both models are consistent with familial aggregation of neural tube defects, in this sample, being due to either the segregation of a recessive major gene or a sibling environmental effect, or both factors. In each case, other environmental factors are also involved. These results were compared to the findings of other studies and discussed in respect to the diversity of the epidemiological features displayed by different populations. Some observations of vertical transmission in a British study and the proportion of affected first cousins, in both France and Great Britain, lead us to reject a possible absence of transmission. We propose a monogenic component with a large influence of environmental factors, some of which may be common to sibs, to explain the occurrence of neural tube defects in this sample.
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