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Ante una malformación congénita de los miembros, es necesaria una evaluación para buscar malformaciones asociadas, con el fin de determinar su carácter aislado o sindrómico. Entonces se puede emprender una investigación etiológica, teniendo en cuenta también el tipo de la anomalía de miembro. Las causas son muy heterogéneas: accidentales, ligadas a una embriofetopatía o genética. Se sospecha en particular una causa genética si la anomalía afecta a varias extremidades y/o es sindrómica y/o si existen antecedentes familiares, pero estos criterios pueden faltar. Sin ser exhaustivos, en este artículo se examinan las principales etiologías de las malformaciones congénitas de los miembros.

Las malformaciones congénitas de los miembros tienen una prevalencia estimada en alrededor del 1,5‰ en recién nacidos y más del doble entre las muertes neonatales. Son muy variadas y se observan de forma aislada o en un marco sindrómico. Alrededor de un tercio de ellas tienen un origen genético. El descubrimiento de las diversas vías de señalización que controlan el desarrollo de la yema del miembro, así como de varios de los genes implicados, ha permitido comprender mejor la génesis de estas malformaciones. Sin embargo, su clasificación no es sencilla, como reflejan las numerosas clasificaciones que figuran en las publicaciones. Para ayudar en el enfoque diagnóstico, se propone una clasificación basada en las anomalías de los principales mecanismos del desarrollo de la yema del miembro. Distingue entre anomalías en el inicio, la identidad, los ejes proximodistal, preaxial-postaxial, dorsoventral, la modelización y la condrogénesis.

Objective: To review the possible craniomaxillofacial deformative consequences associated with ectodermal dysplasias and embryonic malformations, which include dental ageneses.Setting: Oral and Maxillofacial Surgery Department, University Hospital, Lille, France.Patients: Sixteen patients (seven boys and nine girls, aged 4 to 34 years) with pure ectodermal dysplasia (no ectodermal dysplasia syndromes).Interventions: All patients had a clinical examination. Seven (two boys and five girls, aged 4 to 25 years) had undergone plaster casts and radiographic and Delaire's cephalometric studies before being treated.Main Outcome Measures: All patients had tooth ageneses (from hypodontia to anodontia), associated with cutaneous dyshidrosis and hair and nail dystrophy. Most of them had a short face, with an unusual facial concavity, a maxillary retrusion, and a relative mandibular protrusion.Management Results and Discussion: Depending on their ages and their orthopedic abnormalities, patients underwent either dental or prosthodontic, orthodontic, orthopedic, orthognathic, or implant treatment. So as not to interfere with the growth pattern, we preferred to reserve implant and orthognathic surgery for full-grown cases.Conclusions: Oral and maxillofacial surgeons must undertake a comprehensive approach to these patients to improve their dental, masticatory, growing, and orthognathic conditions.

An unreported missense mutation of the ribosomal S6 kinase 2 (RSK2) gene has been identified in two male sibs with a mild form of Coffin-Lowry syndrome (CLS) inherited from their healthy mother. They exhibit transient severe hypotonia, macrocephaly, delay in closure of the fontanelles, normal gait, and mild mental retardation, associated in the first sib with transient autistic behaviour. Some dysmorphic features of CLS (in particular forearm fullness and tapering fingers) and many atypical findings (some of which were reminiscent of FG syndrome) were observed as well. The moderate phenotypic expression of this mutation extends the CLS phenotype to include less severe mental retardation and minor, hitherto unreported signs. The missense mutation identified may be less deleterious than those previously described. As this mutation occurs in a protein domain with no predicted function, it could be responsible for a conformational change affecting the protein catalytic function, since a non-polar amino acid is replaced by a charged residue.

Blau syndrome (MK186580) comprises granulomatous arthritis, iritis, and skin rash, and is an autosomal-dominant trait with variable expressivity. So far it was described in 5 families. We report on a sixth family with severe progression of eye involvement and discuss the nosology with similar diseases, such as early-infantile sarcoidosis. Am. J. Med. Genet. 76:217–221, 1998. © 1998 Wiley-Liss, Inc.

A family with two male cousins affected with myotubular myopathy (MTM) was referred to us for genetic counselling. Linkage analysis appeared to exclude the Xq28 region. As a gene for X linked MTM was recently identified in Xq28, we screened the obligatory carrier mothers for mutation. We found a 4 bp deletion in exon 4 of the MTM1 gene, which originated from the grandfather of the affected children and which was transmitted to three daughters. This illustrates the importance of mutation detection to avoid pitfalls in linkage analysis that may be caused by such cases of germinal mosaicism.