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Biomedical subjects

J M Opitz

Publications and source records attributed to J M Opitz.

At least 55 records · Page 3Linked to original sources

Complete absence or deficiency of one half of the body.

Here we report on an apparently unprecedented case of virtually complete absence of the left half of the body, with resulting severe deformity of the right half. The fetus was stillborn with polyhydramnios at 31 1/2 weeks of gestational age. A second patient may be a mild example of this extraordinary phenomenon with deficiency of organs, predominantly on the left side. The nosology and developmental implications are discussed briefly.

Abnormalities, Severe Teratoid↗

Opitz G/BBB syndrome in Xp22: mutations in the MID1 gene cluster in the carboxy-terminal domain.

The MID1 gene in Xp22 codes for a novel member of proteins containing a RING finger, B-box, coiled-coil and a conserved C-terminal domain. Initially, three mutations in the C-terminal region were found in patients with Opitz G/BBB syndrome, a defect of midline development. Here we have determined the complete gene structure of the MID1 gene and have analyzed all nine exons for mutations in a set of 40 unrelated Opitz G/BBB patients. We now report six additional mutations all clustered in the carboxy-terminal domain of the MID1 protein. These data suggest that this conserved domain of the B-box proteins may play a fundamental role in the pathogenesis of Opitz syndrome and in morphogenetic events at the midline during blastogenesis.

Abnormalities, Multiple↗

Familial broad terminal phalanges with one individual showing additional anomalies.

We describe a family with four relatives showing broad terminal phalanges (BTP) of the fingers and toes. One also had mental retardation, an unusual facial appearance, cleft palate with bifid uvula, and gingival hyperplasia. The BTP anomaly in this family seems to be transmitted as an autosomal dominant trait.

Abnormalities, Multiple↗

Another "new" form, the palagonia type of acrofacial dysostosis in a Sicilian family.

We described another previously apparently unreported form of acrofacial dysostosis (AFD) from Sicily, residing, coincidentally in the same small village as that with the recently delineated Catania AFD. In contra-distinction to the latter, the 4 patients with the Palagonia form of AFD are of normal intelligence, and instead of extensive caries have oligodontia (4), short stature (3), frizzy hair (pili torti) with aplasia cutis verticis (1), mild cutaneous syndactyly of digits 2-5 (4), attenuation of the 4th metacarpals (3/3), unilaterally cleft lip (1), and some vertebral anomalies such as a large atlas (1), mild scoliosis (1), small odontoid process, spina bifida occulta at S1 (1). Casually, this would appear to be an iceberg dominant disorder, with the proposita most severely affected. This could be an X-linked dominant, but more likely an autosomal dominant trait.

Abnormalities, Multiple↗

Autosomal dominant and sporadic radio-ulnar synostosis.

We report on seven cases of congenital radio-ulnar synostosis (RUS). Five were found in the same family and two were sporadic. In six the synostosis was bilateral and consistently involved the proximal end of the radius and ulna. In the familial cases the anomaly was inherited as an autosomal dominant trait and was associated with a Dubois sign and relative shortness of metacarpals number 4 and 5 in two patients, and of number 2 in another patient, and of all phalanges of the 5th fingers. These observations suggest involvement of an ulnar developmental field. RUS does not seem to be rare in the Sicilian population.

Adult↗

Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22.

Opitz syndrome (OS) is an inherited disorder characterized by midline defects including hypertelorism, hypospadias, lip-palate-laryngotracheal clefts and imperforate anus. We have identified a new gene on Xp22, MID1 (Midline 1), which is disrupted in an OS patient carrying an X-chromosome inversion and is also mutated in several OS families. MID1 encodes a member of the B-box family of proteins, which contain protein-protein interaction domains, including a RING finger, and are implicated in fundamental processes such as body axis patterning and control of cell proliferation. The association of MID1 with OS suggests an important role for this gene in midline development.

Abnormalities, Multiple↗

Bilateral radial deficiency with lower limb involvement.

We describe a 10-month-old boy with an unclassified form of radial aplasia with absent thumbs, tibia hypo/-aplasia, and partial absence of toes. Only a few cases with similar limb deficiencies have been published. We try to classify the malformations on the basis of embryological considerations and discuss possible differential diagnosis.

Adult↗

Dubowitz syndrome: review of 141 cases including 36 previously unreported patients.

We review clinical information on 141 individuals with Dubowitz syndrome, 105 reported since 1965, and 36 previously unreported. We define the Dubowitz syndrome phenotype on the basis of clinical descriptions. The facial appearance is characteristic and present in most patients with Dubowitz syndrome. The phenotypic spectrum is quite variable and ranges from normal growth and head circumference with mild psychomotor retardation and lack of eczema to a condition of severe growth retardation, mental retardation, microcephaly, and eczema. Overall, the condition may involve the cutaneous, ocular, dental, digestive, musculoskeletal, urogenital, cardiovascular, neurological, hematological, and immune systems. Characteristic behavior patterns which have not been cited previously are present in our cases; most patients are hyperactive, shy, hate crowds, and like music, rhythm, and vibrations from music speakers, tape recorders, or transmitted through floors. Dubowitz syndrome is an autosomal recessive disorder with possibly increased frequency of parental consanguinity. Heterogeneity cannot be excluded at this time.

Abnormalities, Multiple↗

Kniest dysplasia: radiologic, histopathological, and scanning electronmicroscopic findings.

We describe severe neonatal Kniest dysplasia. Radiological findings in a severe case include short bowed tubular bones with exaggerated metaphyseal flare, moderate platyspondyly with vertical clefts of the vertebral bodies, and characteristically shaped iliac bones. Pathologic findings included a disorganized physeal growth plate, soft crumbly cartilage with a "Swiss-cheese" appearance, and diastase resistant intracytoplasmic inclusions in the resting chondrocytes. Transmission electronmicroscopy showed dilated cisternae of rough endoplasmic reticulum with finely granular material of accumulated protein. Scanning electronmicroscopy documented striking fragmentation and disintegration of collagen fibrils resulting in a web-like pattern and large open cyst-like spaces, and deficiency and disorganization of the collagen fibrils.

Adult↗

Resynthesizing evolutionary and developmental biology.

A new and more robust evolutionary synthesis is emerging that attempts to explain macroevolution as well as microevolutionary events. This new synthesis emphasizes three morphological areas of biology that had been marginalized by the Modern Synthesis of genetics and evolution: embryology, macroevolution, and homology. The foundations for this new synthesis have been provided by new findings from developmental genetics and from the reinterpretation of the fossil record. In this nascent synthesis, macroevolutionary questions are not seen as being soluble by population genetics, and the developmental actions of genes involved with growth and cell specification are seen as being critical for the formation of higher taxa. In addition to discovering the remarkable homologies of homeobox genes and their domains of expression, developmental genetics has recently proposed homologies of process that supplement the older homologies of structure. Homologous developmental pathways, such those involving the wnt genes, are seen in numerous embryonic processes, and they are seen occurring in discrete regions, the morphogenetic fields. These fields (which exemplify the modular nature of developing embryos) are proposed to mediate between genotype and phenotype. Just as the cell (and not its genome) functions as the unit of organic structure and function, so the morphogenetic field (and not the genes or the cells) is seen as a major unit of ontogeny whose changes bring about changes in evolution.

Animals↗

Limb anomalies from evolutionary, developmental, and genetic perspectives.

Coming-on-land by vertebrates during the Devonian was preceded by a 100 million year history of evolution of fins from an early agnathan to a sarcopterygian state with proximal single stylopod bone and probable paired zeugopod bones. There is little disagreement about the homology [Owen, 1837: See Desmond, 1982; Owen, 1849 for a general discussion see Roth, 1988] of these three bones to the corresponding ones of present land vertebrates including those of birds and mammals; or, that the concept of homology in this context may safely be interpreted as meaning structural "identity" by virtue of descent from a common ancestor with a prototypic developmental plan irregardless of the corresponding innervating vertebral segments [qv Roth, 1988]. This extraordinarily conserved body plan in all four classes of tetrapods, including some 4500 living species of mammals, suggests early successful selection, adaptation, and emergence of developmental constraints assuring "proper" succession of proximo-distal epimorphic events and the structural and functional integrity of the autopod. The autopod is the most variable part of the tetrapod limb with humans, in contract to most other primates, retaining its most general form with little modification except for use of the thumb [Ankel-Simons, 1983]. There is also no question about the fact that during the later stages of blastogenesis the limb arises as a prepatterned single morphogenetic field from lateral plate (and somite) mesoderm and overlying ectoderm organizing in concert a single, orthotopic developmentally reactive system of ectoderm-covered mesodermal core with distal apical ectodermal ridge and posterior zone of polarizing activity. This assertion is based on two lines of evidence. First, experimental results [beginning with Harrison and Detweiler in 1918] recognized almost immediately as demonstrating not symmetrical, but "equipotential" fields with identical morphogenetic reaction potential in all vertebrates studied so far. One is tempted to say that these morphological results and interpretations have been, "triumphantly" confirmed by recent molecular work. Second, clinical insights beginning with thalidomide, and then drawing on the acrofacial dysostoses, the associations (VATER), and the discovery of the acrorenal polytopic field defect in humans, which found its explanation in the work of Lash and of Geduspan and Solursh (possibly involving a single molecule, namely, the insulin-like growth factor-I). It is evident that the gross morphological pattern set up in subsequent normal limb development is proximo-distally hierarchical (or at least sequential), and that the complex group of secondary (epimorphic) fields (perhaps as many as 33 as identified by analysis of mendelian mutations) is determined before cellular differentiation of the individual tissue components of the limb. The Anikin [1929] patterns of precartilage condensations, segmentations, and branchings in limb rudiments, while involving a specific type of cell (precartilage mesenchyme) in complex interaction with the extracellular matrix, must be looked at primarily as gross morphogenetic field events rather than as "fine" tissue differentiation sensu stricto. In view of the clinical evidence, the Shubin-Alberch-Oster model of (pre) cartilage events (condensation, segmentation, and branching), while universally valid as such, had best be regarded as events with morphogenetic potential rather than as invariable predictors of final structure.

Animals↗