Genitopatellar syndrome: a new condition comprising absent patellae, scrotal hypoplasia, renal anomalies, facial dysmorphism, and mental retardation.

We report on the association of absent patellae, genital and renal anomalies, dysmorphic features, and mental retardation in seven children (six boys and one girl) belonging to five unrelated families. Flexion deformities of the knees and hips with club feet and absent patellae were consistently observed and scrotal hypoplasia and cryptorchidism were present in all boys (6/6). Dysmorphic features included a coarse face, a large nose with a high nasal bridge, and microcephaly. Other features included renal anomalies (multicystic kidneys or hydronephrosis, 7/7), agenesis of the corpus callosum (4/7), swallowing difficulties, micrognathia (4/7), and pulmonary hypoplasia (3/7). Bilateral hypoplasia of the ischia and brachydactyly were also consistently observed (5/5). In two out of seven cases, prenatal ultrasound detection of microcephaly and renal anomalies led to termination of the pregnancy at 27 weeks. Three children died during the first years of life and the remaining two who survived exhibit severe developmental delay. High resolution cytogenetic studies performed on lymphocytes or fibroblasts or both were normal in all cases. Recurrence in two families suggests an autosomal recessive mode of inheritance. We propose that this unusual association, similar to that observed in a 4 year old boy by Goldblatt et al, represents a new syndrome distinct from previously reported hypoplastic patella syndromes.

Unusual association of juvenile macular dystrophy with congenital hypotrichosis: occurrence in two siblings suggesting autosomal recessive inheritance.

A familial association between juvenile macular dystrophy and congenital hypotrichosis is described in two siblings aged 25 and 23 years. We put forward arguments for locating the retinal alteration at the level of the retinal pigment epithelium and suggest that the hair disorder could be a Marie-Unna type hypotrichosis. This association is transmitted as an autosomal recessive condition.

[An unrecognized etiology of sexual ambiguity: Smith-Lemli-Opitz syndrome or a new entity?]. / Une étiologie méconnue de l'ambiguïté sexuelle: syndrome de Smith-Lemli-Opitz ou entité nouvelle?

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.

[Marfan disease]. / La maladie de Marfan.

After reviewing the main features of the Marfan syndrome (musculoskeletal, ocular, cardiovascular, pulmonary abnormalities), its autosomal dominant inheritance with high penetrance but variable phenotype and presence of "soft" conditions preventing an easy diagnosis, the authors report their own data relevant to 73 probands: ratio of each clinical manifestation, state of 34% of familial cases and display of a paternal age effect in the sporadic cases. The pathogenic defect is unknown as like the location of the gene. The difficulties of the genetic counseling are then approached: unpredictability of the severity and of the prognosis in the unborn children of an affected patient, benefit of the echocardiography in the management of people at risk.

Genetic counselling, carrier detection, and prenatal diagnosis in hemophilia. A service experience.

Our experience over three years (1984-1986) is described in carrier detection and prenatal testing for hemophilia. We have analysed 50 families: 37 hemophilia A and 13 hemophilia B, 22 isolated cases and 28 familial. Eighty-three women belonging to this panel asked for a genetic risk. Pedigree and coagulation studies were performed to estimate genetic risks according to the Bayesian method. At this point, 40% of the females at risk were recognized carriers before the DNA analysis. Molecular biology allowed the detection of only 7% more carriers and the exclusion of 34%. In 19% of the cases, it was impossible to estimate the genetic risk because the families were uninformative for the DNA polymorphisms used. Twenty-two prenatal diagnoses were performed; 3 affected male fetuses were recognized by DNA analysis and pregnancies were terminated. Eleven healthy boys were born.

[Epidemiological and genetic study of 3 congenital cardiopathies with neonatal disclosure]. / Etude épidémiologique et génétique de trois cardiopathies congénitales à révélation néonatale.

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.

[Autosomal recessive metaphyseal chondrodysplasia and Hirschsprung's disease]. / Chondrodysplasie métaphysaire récessive autosomique et maladie de Hirschsprung.

Two unrelated patients with Hirschsprung disease and very short stature since birth are reported. Attention is drawn to the early roentgenographic signs of recessive McKusick metaphyseal chondrodysplasia syndrome or cartilage-hair hypoplasia syndrome. Some, but not all, patients with this chondrodysplasia exhibit anomalies of the hair, neutropenia and immune deficiency. Presence of congenital megacolon is apparently not exceptional. Nosologic limits are discussed.

Human genes involved in chromatin remodeling in transcription initiation, and associated diseases: An overview using the GENATLAS database.

Chromatin structure is inextricably linked to transcription regulation and differentiation. It consists of a multicomponent system, and impairments in such complex arrays may elicit dramatic biological effects and diseases. We present an overview of human genes involved in chromatin remodeling, which consist of the histone acetyltransferase/deacetylase system and the SWI/SNF-like complexes containing DNA-dependent ATPase activity. Special attention is given to the functional and physical interactions in which these components are involved, notably as transcriptional coactivators and/or corepressors of a large variety of genes. Linking seemingly distinct pathways allows integration of individual components into complex genetic and molecular processes and assessment of the underlying molecular bases of diseases. This was performed using GENATLAS (http://www.infobiogen.fr/), a gene database which compiles the information relevant to the mapping efforts from the published literature.

Prenatal prediction of Werdnig-Hoffmann disease using linked polymorphic DNA probes.

Werdnig-Hoffmann disease is a common autosomal recessive neuromuscular disorder that results in paralysis and death. No treatment to prevent this disease or to alter its unremitting course has been found. Recently, linkage analysis with cloned DNA probes has shown that the mutation causing Werdnig-Hoffmann disease is located on chromosome 5q12-q14. We performed genetic analysis for the prenatal diagnosis of Werdnig-Hoffmann disease in seven at risk families. Two fetuses were diagnosed as being affected and the remainder as unaffected, and this was confirmed after birth. This study shows that prenatal diagnosis of Werdnig-Hoffmann disease has become feasible.