Human Malformation Syndromes Research Articles

Sex reversal by loss of the C-terminal transactivation domain of human SOX9.

Haploinsufficiency for SOX9 has recently been identified as the cause for both campomelic dysplasia (CD), a human skeletal malformation syndrome, and the associated autosomal XY sex reversal. SOX9 contains a putative DNA-binding motif known as the high-mobility group (HMG) domain characterizing a whole class of transcription factors. We show in cell transfection experiments that SOX9 can transactivate transcription from a reporter plasmid through the motif AACAAAG, a sequence recognized by other HMG domain transcription factors. By fusing all or part of SOX9 to the DNA-binding domain of yeast GAL4, the transactivating function was mapped to a transcription activation (TA) domain at the C terminus of SOX9. This non-acidic TA domain is evolutionarily conserved and rich in proline, glutamine and serine. With one exception, all SOX9 nonsense and frame shift mutations described so far in CD/sex reversal patients lead to truncation of the TA domain, suggesting that impairment of gonadal and skeletal development in these cases results, at least in part, from loss of transactivation of genes downstream of SOX9.

Clinical Delineation of Multiple Congenital Anomalies*

Abstract The evaluation of multiple congenital anomalies requires several points.1. Definite diagnostic criteria of each malformation and its precise description are of importance in the diagnosis of malformation syndromes.2. Complete family studies improve the accuracy of diagnosis and provide us with valuable information in genetic counselling.3. The use of good reference books and computer‐aided diagnosing systems are effective measures.4. It is of great importance to circulate case documents, and to exchange information on the diagnosis, among clinical dysmorphologists.5. It is crucial to combine the alert clinician's eye and the epidemiologic approach for seeking etiologic associations.6. Animal models of human malformation syndromes contribute much toward deep understanding of deviated morphogenesis.

A administração de esteróides sexuais no inicio da gravidez provoca malformações fetais?

On the basis of recent literature review we cannot assume that the use of human female sex steroids at the beginning of pregnancy is related to human malformation syndromes in organs and tissues that are not those of the genital area. The literature references do not give us information which permits us to come to the conclusion that in special conditions to be better defined, these hormones will play a role in the causes of fetal malformations, based upon a dose effect or interaction with other environmental agents. We presume that this subject will be better studied in a prospective investigation with a large number of cases. Until the conclusion of such a study the use of sex female hormones during pregnancy should be avoided.

The community of human malformation syndromes that shares ectodermal dysplasia and deformities of the hands and feet

Syndromes of human congenital malformation may be classified be recognizing communities of syndromes that share multiple phenotypic similarities involving their principal diagnostic features. A community of syndromes that shares various expressions of ectodermal dysplasia and various deformities of the hands and feet is proposed; these syndromes are divisible into two classes according to the presence or absence of anomalies in the nasal or labial regions of the face. The dysmorphogenetic validity of the division is supported by the fact that the syndromes without nasal or labial anomalies have a high frequency of sensorineural deafness as one expression of ectodermal dysplasia whereas those without such anomalies do not. The usefulness of such a syndromal community as a base for evolving a taxonomic scheme of dysmorphogenetic relatedness amongst different syndromes is illustrated.

A community of human malformation syndromes involving the Müllerian ducts, distal extremities, urinary tract, and ears.

Abstract“Syndrome fever” is a term used to characterize the prolific publication of “new” human congenital malformation syndromes in the last decade. One way to manage syndrome fever, that is, to assimilate and utilize efficiently its valuable informational by‐product, is to create nosologic communities composed of member‐syndromes which have close general and specific phenotypic similarities. The phenotypic community approach to human mal‐formation syndrome taxonomy is applicable to rare, family‐specific syndromes, to well‐known syndromes that have achieved firm, independent identities, and to mixtures of the two. A community of six syndromes, four of them apparently rare, is proposed. All share uterovaginal malformation, but neither this type nor any other single type of malformation is essential for a syndrome to merit membership in the community. Five of the six syndromes have distinc‐tive and and/or foot malformations. Four of the six share malformations of the urinary tract; in a fifth urinary incontinence probably reflects a subtle dysmorphism. Three of the six syndromes have anomalies of the aural appa‐ratus; in two this involves an association between severe renal dysgenesis and middle ear ossicle defects. The sharing of similar malformations involving several systems suggests that the respective causes of the syndromes act on the same developmental pathway(S). All six syndromes have occurred in a familial distribution; four are probably determined by major mendelian genes. Malformations of the axial skeleton are rare, but those of the distal extremities are common, in the familial syndromes belonging to the group. The reciprocal tendency is found in sporadic occurrences of severe uterovaginal dysgenesis (Rokitansky‐Küster‐Hauser syndrome) and in those with so‐called nonspecific female pseudohermaphroditism.