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PubMed1982

The structure and function of dermal connective tissue in normal individuals and patients with inherited connective tissue disorders.

Normal, human dermis is a dense, interwoven collagen and elastic matrix organized into papillary and reticular regions. the papillary dermis is a narrow zone beneath the epidermis which includes an even narrower subepidermal connective tissue band beneath the basal lamina. The reticular dermis has superficial intermediate and deep reticular zones. Each region is distinguished by the organization of the fibrous connective tissue. In this review, the structure, composition and function of each region of the normal dermis is surveyed and alterations in the tissue that have been recognized ultrastructurally in skin from patients with inherited connective tissue diseases are discussed. A molecular defect in a connective tissue molecule can be expressed phenotypically at one or more levels of dermal organization and can modify the structure of other matrix components. In some cases, the entire interwoven pattern of the dermis is altered; in others, the dermis retains the interwoven pattern and alterations are expressed as defects in the association of fibrils into fibers and fiber bundles. Abnormalities in the size, packing and relationships of fiber bundles also can occur. These changes involve the collagen matrix primarily. Depletion or exaggeration of elastin, or of the amorphous ground substance can also influence the organization of collagen and of the overall dermal architecture. The alterations described are illustrated with scanning electron micrographs of skin from patients with inherited connective disorders and are discussed in terms of the mechanical abnormalities of the tissue.

Collagen↗
PubMed2006

Climate change, body size evolution, and Cope's Rule in deep-sea ostracodes.

Causes of macroevolutionary trends in body size, such as Cope's Rule, the tendency of body size to increase over time, remain poorly understood. We used size measurements from Cenozoic populations of the ostracode genus Poseidonamicus, in conjunction with phylogeny and paleotemperature estimates, to show that climatic cooling leads to significant increases in body size, both overall and within individual lineages. The magnitude of size increase due to Cenozoic cooling is consistent with temperature-size relationships in geographically separated modern populations (Bergmann's Rule). Thus population-level phenotypic evolution in response to climate change can be an important determinant of macroevolutionary trends in body size.

Animals↗
PubMed2001

Isolation of human plasma-inducible, growth phase- and temperature-regulated gene fusions in Streptococcus pyogenes using a Tn917-lacZ transposon.

Streptococcus pyogenes is capable of causing a variety of human diseases ranging from superficial or deep tissue infections to non-infectious post-streptococcal infection sequelae. In this paper, we report the use of a Tn917-lacZ transposon to isolate random lacZ transcription fusions in the S. pyogenes chromosome. Libraries of random Tn917-lacZ mutants were generated in a representative opacity factor positive strain CS101 (M49) and an opacity factor negative strain 1881 (M1). Several different mutant phenotypes were isolated. These included: temperature-regulated promoters, growth phase/cell density-regulated promoters and a human plasma-inducible promoter. Expression of the temperature-regulated fusions was 5-10-fold higher when grown at 30 degrees C compared to growth at 37 degrees C. The growth phase-regulated fusions were induced 30-fold at late exponential phase and were repressed by a diffusible S. pyogenes factor(s). Expression of the human plasma-inducible fusion was induced 10-15-fold by human plasma or sera, 4-fold by rabbit sera and was repressed by horse and mouse sera. In addition, hemolysin negative and capsule over expression mutants were isolated. These results demonstrate the utility of Tn917-lacZ mutagenesis for the identification of S. pyogenes promoters.

Artificial Gene Fusion↗
PubMed1999

Distribution of fast myosin heavy chain-based muscle fibres in the gluteus medius of untrained horses: mismatch between antigenic and ATPase determinants.

The distribution of muscle fibres classified on the basis of their content of different myosin heavy chain (MHC) isoforms was analysed in muscle biopsies from the gluteus medius of adult untrained horses by correlating immunohistochemistry with specific anti-MHC monoclonal antibodies and standard myofibrillar ATPase (mATPase) histochemistry. Percutaneous needle biopsies were taken at 3 depths (20, 40 and 60 mm) from 4 4-y-old Andalusian stallions. The percentage of 'pure' I MHC fibres increased whereas that for pure IIX MHC fibres decreased from the most superficial to the deepest sampling site. Within the fast fibres, types IIA and IIAX MHC-classified fibres were proportionately more abundant in the deepest sampling site than in the superficial region of the muscle. The immunohistochemical and histochemical characterisation of a large number of single fibres (n = 1375) was compared and correlated on a fibre-to-fibre basis. The results showed that 40% of the fibres analysed were pure type I (expressing only MHC-I); they showed correct matching between their antigenic and mATPase determinants. In contrast, within the fast fibres, a considerable proportion of fibres were found showing a mismatch between their immunohistochemical and mATPase profiles. The most common mismatched fibre phenotypes comprised fibres displaying coexpression of both fast MHCs when analysed by immunocytochemistry, but showing an mATPase profile similar to typical IIX fibres (moderate mATPase reaction after preincubation at pH 4.4). Considered altogether, the total mismatched fibres represented only 4.2% of the whole fast fibre population in the superficial region of the muscle, but their proportion increased to 15.6% and 38.4% in the middle and deep regions, respectively, of gluteus medius. It is concluded that a considerable number of hybrid fast MHC IIAX fibres are present in the gluteus medius of untrained horses, suggesting that equine type II fibres have probably been misclassified in numerous previous publications based on the use of histochemistry alone. This has important implications in attempts to study the physiological properties of fast fibre types adequately in horses.

Animals↗
PubMed1999

Growth hormone improves body mass recovery with refeeding after chronic undernutrition-induced muscle atrophy in aging male rats.

The effects of growth hormone (GH) administration and refeeding after chronic undernutrition (UN) were investigated in Fischer 344 male rats aging into senescence (24.5 mo of age) during UN initiated at 12.5 mo of age that produced muscle atrophy and a 50% decrease in body mass. Muscle mass, protein, myosin heavy-chain (MHC) composition and circulating testosterone levels were measured and compared to controls with free access to food. Within 9 wk, refeeding + GH restored body mass to control levels, whereas it was still decreased with refeeding alone. By 24.5 mo of age, refeeding alone restored body mass, while addition of GH resulted in overshoot. UN uniformly decreased mass of the gastrocnemius, extensor digitorum longus, soleus and diaphragm muscles to 50-60% of controls. Refeeding and refeeding + GH restored these losses with some overshoot of gastrocnemius muscle suggesting hypertrophy. UN more than doubled slow Type I MHC composition and approximately halved fast Type IIB and IIX MHC in the deep gastrocnemius muscle while it increased Type IIA MHC in the diaphragm. Refeeding and refeeding + GH reversed these shifts. MHC shifts in the extensor digitorum longus and soleus muscles were not statistically significant, whereas UN increased fast Type IIA MHC followed by decrease with refeeding + GH. UN decreased testosterone levels to nearly zero followed by restoration with refeeding and refeeding + GH. We conclude that the phenotype of mixed-MHC muscles such as the gastrocnemius and diaphragm are most affected by chronic UN, which is reversible with refeeding and refeeding + GH. These alterations were associated with changes in circulating testosterone, which may be a key regulatory element in these processes.

Aging↗
PubMed1999

Ultrastructural changes of erythrocyte membrane skeletons in chorea-acanthocytosis and McLeod syndrome revealed by the quick-freezing and deep-etching method.

The shapes of acanthocytic erythrocytes have been thought to be related to changes of the organization of the membrane components. In this study, acanthocytes from a patient with chorea-acanthocytosis and a patient with McLeod syndrome were examined. These acanthocytes had a greater tendency to form spikes than normal erythrocytes in an incubation culture system, indicating their weakness against membrane tension. The membrane skeletons of erythrocytes from both patients were examined by our erythrocyte-splitting method followed by the quick-freezing and deep-etching method. The ultrastructural organization of the membrane skeletons was heterogeneous even in individual erythrocytes, indicating regional changes in the compactness of their meshworks. In the process of erythrocyte splitting, some erythrocyte membranes became reversed and protruded into the cytoplasmic side. In these regions, there were fewer filamentous structures. The focal membrane skeletal changes, which are probably one of the factors that induce the phenotype of an acanthocytic erythrocyte, were demonstrated for the first time by this method.

Acanthocytes↗
PubMed2001

[Clinical features of autosomal dominant spinocerebellar ataxias genetically unclassified into any known triplet-repeat diseases].

To clarify the clinical features of genetically unclassified autosomal dominant spinocerebellar ataxias (AD-SCAs) treated in our hospital, we retrospectively analyzed the clinical findings of patients who could not be molecularly classified into SCA types 1 through 3, 6 through 8, 12 and dentato-rubro-pallido-luysian atrophy (DRPLA). The clinical findings of 19 patients from 15 different families which form 14 percent of all patients with different types of AD-SCAs (136 patients, 105 families) were collected. Based on these, 17 patients from 13 families showed late-onset (mean age at onset: 46 years old) and slowly progressive truncal and limb ataxias of cerebellar origin. Some of them showed gaze-evoked nystagmus, increased deep reflexes without Babinski sign, tremor, mildly decreased vibration sense and mild rectourinary disturbances. All but one were still ambulatory after 15 years of their mean disease duration. An earlier disease onset in successive generations was observed in 8 families. Brain MRIs revealed cerebellar atrophy predominantly in the anterior vermis in all the patients and mild brainstem atrophy in only 3 patients. Although the clinical phenotype manifested by most of the genetically unclassified AD-SCAs is similar to that of SCA6, whether the phenotype is caused by expansion of triplet repeats or some mutations in a single gene or different mutations in various genes is still unclarified.

Adult↗
PubMed1999

Clinical range and MRI in Creutzfeldt-Jakob disease with heterozygosity at codon 129 and prion protein type 2.

A 68 year old woman with sporadic Creutzfeldt-Jakob disease is described, who neither showed characteristic EEG abnormalities nor a positive test of the neuronal protein 14-3-3 or neuron specific enolase (NSE) in CSF, despite a clinical presentation with ataxia of cerebellar type, rapidly progressive dementia, myoclonus, and marked hyperintense signal abnormalities in the deep cortical layers and the basal ganglia on T2 and diffusion weighted MRI. Moreover she showed atypical clinical features with a syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH) and a peripheral sensorimotor polyneuropathy. Whether these disturbances are independent of Creutzfeldt-Jakob disease or a feature of it is discussed. It has recently been shown that in Creutzfeldt-Jakob disease different clinical and pathological phenotypes correlate with the polymorphism at codon 129 of the prion protein gene (PRNP) and the type of the protease resistant fragment that accumulates in the brain. According to the new classification at least six sporadic variants of Creutzfeldt-Jakob disease exist. The molecular genetic analysis showed heterozygosity of PRNP at codon 129 for methionine and valine and the presence of PrP(CJD) type 2 in the brain of this patient. As a new feature of changes on MRI, striking cortical changes of hyperintense signals are described in diffusion weighted as well as T2 weighted MRI that directly correlate with the histomorphological spongy degeneration of the brain in this region. In cases of rapidly progressive dementia, Creutzfeldt-Jakob disease always needs to be considered even if unusual features are present and current diagnostic criteria are not in favour of this disease.

Aged↗
PubMed2004

Bioconvective pattern formation of Tetrahymena under altered gravity.

Bioconvection is a result of the negative gravitactic behavior of microorganisms. When the top-heavy density gradient generated by gravitaxis grows sufficiently large, an overturning convection occurs leading to a formation of characteristic patterns, which involve highly concentrated aggregation of cells into extended two-dimensional structures. Although gravity is a crucial factor, few experiments have been done with reference to gravity as an experimental variable. In order to gain an insight into the hydrodynamic as well as biological dependence of the convective motion on gravity, we investigated changes in bioconvective patterns of Tetrahymena under altered gravity acceleration generated by a long-arm centrifuge. Bioconvective patterns recorded of three different cell strains (T. pyriformis, T. thermophila and its behavioral mutant, TNR) were analyzed quantitatively using space-time plot and Fourier analysis. For example, under subcritical conditions, when T. pyriformis (1.0 x 10(6) cells ml(-1)) was placed in a 2 mm-deep chamber, no spatial pattern was observed at 1 g. When the suspension was centrifuged, however, patterns began to appear as acceleration increased over a critical value (1.5 g), and then remained steady. The formation was reversible, i.e. the patterns disappeared again as acceleration decreased. Under supracritical conditions, i.e. when a suspension of the same density was placed in a 4 mm-deep chamber, a steady state pattern was formed at 1 g. The pattern spacing in the steady state was observed to decrease stepwise in response to step increases in acceleration. Fourier analysis demonstrated that for TNR the mean wave number changed almost simultaneously with step changes in acceleration, whereas the responses were less sharp in the wild-type strains. This may suggest that the locomotor phenotype of the cell, such as its avoiding response ability, has a crucial role in bioconvective pattern formation. These findings are discussed in relation to former theoretical studies.

Animals↗
PubMed1985

Curative intravenous adoptive immunotherapy of Meth A murine sarcoma. A histologic and immunohistochemical assessment.

Intravenous administration of 1.5 X 10(8) syngeneic spleen cells from immune animals resulted in the complete eradication of established Meth A soft tissue sarcomas in (C57BL/6 X BALB/c) F1 mice. In mice receiving a single injection of immune spleen cells 4 days after tumor implantation in the abdominal wall, the tumors continued to grow for approximately 1 week before undergoing regression. This delay before adoptive immunity is expressed is thought to represent the time needed for the passively transferred cells to give rise to a host response of sufficient magnitude to destroy the tumor. None of the mice receiving a similar number of control spleen cells were cured of their sarcomas. Successful therapy was dependent upon the transfer of viable, immune T lymphocytes and required prior irradiation of the tumor-bearing host in order to remove suppressor T cells. Utilizing sequential histologic and immunohistochemical techniques, we attempted to characterize the cellular events of tumor regression. The earliest histologic difference between animals treated with immune and nonimmune lymphocytes was in the number of lymphocytes detected at the perimeter of the tumor in specifically immunized mice on day 6. There was also a striking difference between animals treated with immune versus nonimmune lymphocytes in the intensity and timing of the acute inflammatory response beginning on day 8. The "front" of immunologically mediated tumor destruction appeared at the lateral and deep borders of the implanted sarcomas and progressed inward. During the period of active tumor regression T lymphocytes reactive with a biotinylated mouse anti-Thy 1.2 monoclonal antibody were increased in frozen sections of tumors in mice receiving immune cells relative to the controls. During the first 3 weeks following adoptive transfer of lymphocytes, T cells reactive with Lyt-1 biotinylated mouse monoclonal antibody (helper/inducer phenotype) outnumbered their Lyt-2 (suppressor/cytotoxic) counterparts in frozen sections of tumor from both specifically immunized and control mice. By the end of the 4th week of the experiment, the sarcomas were completely eradicated in all mice receiving immune cells. The previous tumor beds were occupied by collections of lipid-laden macrophages, lymphocytes, plasma cells, and fibroblasts. Despite vigorous but delayed acute and chronic inflammatory responses at the tumor perimeters in the control mice, these tumors all progressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Ultrastructural analyses of the Caenorhabditis elegans rol-6 (su1006) mutant, which produces abnormal cuticle collagen.

Roller mutants of Caenorhabditis elegans rotate around their long axis and move in circular paths. Isolation and sequence of the rol-6 gene of C. elegans have shown that it encodes a cuticle collagen. In this paper, we describe the morphological alterations seen in the cuticle of the right roller mutant rol-6 (su1006) at the ultrastructural level. Deep-etched replica analyses showed that the honeycomb elements, fibers organized in a pentagonal fashion above the fishbone fibrous layer, completely fill the intermediate layer, which is observed to be largely empty spaces in the wild-type strain. The honeycomb fibers appear to connect the cortical and basal regions of the mutant cuticle. These fibers are likely to be involved in generating the helical twist of the mutant animals. Deep-etched replicas also revealed a delicate network of filaments on the nematode surface.

Animals↗
PubMed1988

Angiocentric T-cell lymphoma of the skin. An aggressive lymphoma distinct from mycosis fungoides.

Among 37 consecutive cases of malignant lymphoma in which the skin was either the only site of disease or one of the prominent sites of initial involvement, 19 cases had a distinctive histological appearance. These cases corresponded to what has been termed "angiocentric lymphoma," and all were found to exhibit a T-cell phenotype either by frozen-section immunohistochemistry or by using monoclonal antibodies reactive in paraffin sections. There were nine men and 10 women; the mean age was 48.2 years. The lesions were nodular and were either ulcerated or had intact skin. One case presented with involvement of one anatomical region of skin, five had involvement of multiple regions of skin, and 13 had concurrent extracutaneous disease. The disease pursued an aggressive course and was not uncommonly resistant to treatment. Histologically, the lymphomatous infiltrate occurred predominantly in the mid to deep dermis with involvement of the subcutaneous layer. The pattern was mainly perivascular and peri-adnexal with or without confluence; the overlying epidermis and papillary dermis were often spared. A prominent feature was invasion of small or large blood vessels by lymphoma cells. Eight cases showed extensive coagulative necrosis of the neoplastic and normal tissues, and 12 cases showed intraneural invasion. The neoplastic lymphoid cells consisted of either a monomorphous population or a variable mixture of small, medium-sized, and large cells with stippled chromatin and distinct nucleoli. Although the nuclei were often irregularly folded, few exhibited a cerebriform configuration. The cytoplasm was pale to clear. These cases exhibit a remarkable histological similarity to the T-cell lymphomas of the nasal/nasopharyngeal region; in addition, there are features that overlap with so-called lymphomatoid granulomatosis of the skin.

Adult↗
PubMed2000

Digital ulcers and necroses: novel manifestations of angiocentric lymphoma.

We describe a patient with angiocentric lymphoma whose presenting features were multiple areas of digital ulceration and necrosis, including deep ulcers on both great toes. He lacked the lateral halves of both earlobes because of multiple ulcers. Skin biopsy revealed a patchy and diffuse infiltrate of lymphoid cells with nuclear atypia in the dermis and subcutaneous tissue. Angiocentric and angiodestructive features of the lymphoid cells, a prominent histiocytic infiltrate and some epithelioid cell granulomas were found. The results of immunohistochemical staining showed a T-cell phenotype, and showed positive staining for apoptosis. He died in July 1999. Peripheral vascular disturbances including Raynaud's phenomenon, digital skin ulcers and necroses are novel clinical symptoms in patients with angiocentric lymphoma, which should be added to the differential diagnosis in patients with peripheral vascular disturbances.

Adult↗
PubMed2003

Bone marrow stem cells contribute to healing of the kidney.

A variety of recent studies support the existence of pathways, in adult humans and rodents, that allow adult stem cells to be surprisingly flexible in their differentiation repertoires. Termed plasticity, this property allows adult stem cells, assumed until now to be committed to generating a fixed range of progeny, on relocation to switch to make other specialized sets of cells appropriate to their new niche. Cells normally present within the bone marrow seem particularly flexible and are able to contribute usefully to many recipient organs. In studies of the liver, bone marrow-derived cells are seen with specialized structural and metabolic adaptations commensurate with their new locations, and these may be abundant, even sufficient, to rescue recipient mice from genetic defects and with evidence that they have proliferated in situ. In the kidney, several studies provide evidence for the presence of "reprogrammed" cells, but in most, it remains possible that cells arrive and redifferentiate but are no longer stem cells. Nevertheless, that appropriately differentiated cells are delivered deep within organs simply by injection of bone marrow cells should make us think differently about the way organs regenerate and repair. Migratory pathways for multipotential cells could be exploited to effect repairs using an individual's own stem cells, perhaps after gene therapy. This concept makes it clear that a transplanted organ would in time become affected by the genetic susceptibilities of the recipient, because of phenotypes that are expressed when trafficking cells incorporate and differentiate.

Animals↗
PubMed2006

Interactions between predator- and diet-induced phenotypic changes in body shape of crucian carp.

Predator cues and diet, when studied separately, have been shown to affect body shape of organisms. Previous studies show that the morphological responses to predator absence/presence and diet may be similar, and hence could confound the interpretation of the causes of morphological differences found between groups of individuals. In this study, we simultaneously examined the effect of these two factors on body shape and performance in crucian carp in a laboratory experiment. Crucian carp (Carassius carassius) developed a shallow body shape when feeding on zooplankton prey and a deep body shape when feeding on benthic chironomids. In addition, the presence of chemical cues from a pike predator affected body shape, where a shallow body shape was developed in the absence of pike and a deep body shape was developed in the presence of pike. Foraging activity was low in the presence of pike cues and when chironomids were given as prey. Our results thereby suggest that the change in body shape could be indirectly mediated through differences in foraging activity. Finally, the induced body shape changes affected the foraging efficiency, where crucians raised on a zooplankton diet or in the absence of pike cues had a higher foraging success on zooplankton compared to crucian raised on a chironomid diet or in the presence of pike. These results suggest that body changes in response to predators can be associated with a cost, in terms of competition for resources.

Animals↗
PubMed2001

13-cis-retinoic acid causes patterning defects in the early embryonic rostral hindbrain and abnormal development of the cerebellum in the macaque.

BACKGROUND: We have previously reported that exposure of embryos to 13-cis-retinoic acid (cRA) results in an abnormal phenotype of the fetal cerebellum. In this study, we analyzed early changes in the cerebellar anlagen (midbrain-hindbrain junction) as well as lesions of the fetal cerebellar vermis after a teratogenic dosing regimen of cRA in the macaque model. METHODS: We examined embryo coronal sections of the midbrain-hindbrain junction immunostained for Pax-2, Engrailed-2 (En-2) and Krox-20. To characterize the cerebellum foliation and fissure formation processes, we analyzed vermal cortical cell layer development and the number and depth of the major fissures on sagittal sections of fetal vermis. We also examined Purkinje cell development in vermal sections immunostained for CD3. RESULTS: Compared with controls, there was a consistent truncation of the midbrain-hindbrain region of early embryos exposed to cRA. The cRA-induced fetal vermis lesions included inhibition in its anteroposterior growth, altered folial patterning, a general loss of prominence of the fissures accompanied by a total loss of sublobular fissures, and changes in cortical cell layer development. CD3(+) Purkinje cells were abnormally dispersed deep into the molecular layer in the vermis. CONCLUSIONS: Our findings indicate that the effects of cRA on the developing cerebellum involve interference with the hierarchy of complex cellular and genetic interactions that lead to the growth and subdivision of the cerebellum into smaller units. The regional vermal defects may be related to early postnatal functional deficits.

Animals↗
PubMed1999

Blockade of kit signaling induces transdifferentiation of interstitial cells of cajal to a smooth muscle phenotype.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) serve as pacemaker cells and mediators of neurotransmission from the enteric nervous system to gastrointestinal muscles. ICC develop from mesenchymal cells that express c-Kit, and signaling via Kit receptors is necessary for normal development of ICC. We studied the fate of functionally developed ICC after blockade of Kit receptors to determine whether ICC undergo cell death or whether the phenotype of the cells is modified. The fate of undeveloped ICC was also investigated. METHODS: Neutralizing, anti-Kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. ICC in the small intestine were examined by immunohistochemistry and electron microscopy. Occurrence of apoptosis was also assayed. RESULTS: When Kit receptors were blocked, ICC nearly disappeared from the small intestine. Apoptosis was not detected in regions where ICC are normally distributed. Remaining Kit-immunopositive cells in the pacemaker region of the small intestine developed ultrastructural features similar to smooth muscle cells, including prominent filament bundles and expression of the muscle-specific intermediate filament protein, desmin, and smooth muscle myosin. ICC of the deep muscular plexus normally develop after birth in the mouse. Precursors of these cells remained in an undifferentiated state when Kit was blocked. CONCLUSIONS: These data, along with previous studies showing that ICC in the pacemaker region of the small intestine and longitudinal muscle cells develop from the same Kit-immunopositive precursor cells, suggest inherent plasticity between the ICC and smooth muscle cells that is regulated by Kit-dependent cell signaling.

Animals↗
PubMed2006

Prenatal phenotypic overlap of Costello syndrome and severe Noonan syndrome by tri-dimensional ultrasonography.

BACKGROUND: Prenatal diagnosis of multiple congenital anomalies is difficult, and usually molecular biology cannot immediately confirm the suspected syndrome. Fetal dysmorphology is useful tool in the diagnosis process, with limitations. METHODS: We report the thorough prenatal investigation by 2D and 3D ultrasonography in a case of suspected Costello syndrome. RESULTS: Prenatal abnormalities were: increased nuchal translucency, polyhydramnios, bilateral pyelectasis and ventriculomegaly. Ultrasonographic morphological fetal face analysis found abnormal thickness of the skin in the prefrontal area, thick dysplastic ears, thick lips and deep-set creases in the hands and feet. As Costello and Noonan syndromes overlap, a PTPN11 analysis was done, with presence of a mutation (T854C). CONCLUSION: Prenatal overlap of feature of severe Noonan syndrome and Costello syndrome is confirmed, with dysmorphological similarities, due to edema of fetal skin in face and extremities.

Abnormalities, Multiple↗