Biomedical subjects

R Goldberg

Publications and source records attributed to R Goldberg.

At least 73 records · Page 4Linked to original sources

PubMed1997

Health insurance coverage and outcome following acute myocardial infarction. A community-wide perspective.

BACKGROUND: Several studies have suggested that type of medical insurance coverage is associated with hospital utilization rates and receipt of selected diagnostic or treatment approaches. To our knowledge no studies, however, have examined the relation between medical insurance coverage and short-term outcomes following acute myocardial infarction (AMI) from a multihospital, community-wide perspective. OBJECTIVE: To examine the association between medical insurance coverage and in-hospital case-fatality rates as well as length of hospital stay following AMI. METHODS: The study sample consisted of 3735 residents of the Worcester, Mass, metropolitan area hospitalized with validated AMI during 1986, 1988, 1990, 1991, and 1993 at all metropolitan Worcester hospitals. Data were obtained from the review of medical records. Patients were stratified into 5 medical insurance groups for purposes of analysis: private or commercial (n = 711), Medicaid (n = 101), Medicare (n = 1991), health maintenance organization (n = 741), and self-pay or other (n = 191). Crude and multivariable-adjusted analyses were used to examine the relation between medical insurance coverage and length of hospital stay and in-hospital case-fatality rates following AMI. RESULTS: In-hospital case-fatality rates during the period under study were 7.7%, 11.9%, 21.4%, 9.3%, and 10.0% in the 5 medical insurance groups, respectively. After adjusting for several factors that may affect in-hospital mortality, relative to the referent group of private or commercial insurance patients (odds ratio, 1.0), the multivariable-adjusted odds for dying during the acute hospitalization were 0.87 (95% confidence interval [CI], 0.56-1.36) for health maintenance organization patients, 1.22 (95% CI, 0.55-2.68) for Medical patients, 1.25 (95% CI, 0.85-1.84) for Medicare patients, and 1.21 (95% CI, 0.60-2.44) for self-pay or other patients. The mean length of hospitalization after excluding patients with a prolonged hospitalization was 10.1 days for private or commercial insurance patients, 9.4 days for health maintenance organization patients, 10.9 days for Medicaid patients, 11.1 days for Medicare patients, and 9.8 days for self-pay or other patients. No significant differences in the average duration of hospitalization were seen between the medical insurance groups after controlling for potential confounding variables. CONCLUSIONS: The results of this population-based study suggest that patient insurance status is not significantly associated with either length of hospital stay or short-term mortality following AMI. Other demographic and clinical prognostic factors appear to be more important predictors of short-term outcome in this patient population.

Adult↗

PubMed1997

Pectin methylesterases from poplar cambium and inner bark: localization, properties and seasonal changes.

In the course of a study on the early events of cambial derivative differentiation in Populus x euramericana, seasonal changes in the pattern of pectin methylesterase (PME, EC 3.1.1.11) isoforms were followed. During the resting season, cell wall extracts contained mainly alkaline isoforms with an M(r) around 55 kDa and optimal pH between 5.6 and 6.0. Neutral isoforms with an M(r) around 35 kDa and optimal pH between 6.0 and 6.6 predominated in the extracts during the period of high meristematic activity. In the active cambial initials and in their immediate derivatives, the enzymes were immunolocalized exclusively in the dictyosomes. In older cells, they were present both in dictyosomes and in wall junctions. These results indicate that exportation of neutral PMEs towards the walls might be considered as an early marker of differentiation in cambial derivatives.

Carboxylic Ester Hydrolases↗

PubMed1997

MR imaging of soft tissues adjacent to orthopaedic hardware: techniques to minimize susceptibility artefact.

This article demonstrates and compares imaging of orthopaedic hardware (fixation plates, screws, Kischner wire and prostheses) using gradient-echo, spin-echo and fast spin-echo sequences. It describes simple techniques which minimize susceptibility artefact induced by these components at magnetic resonance (MR) imaging, allowing visualization of adjacent soft tissues. The article emphasizes the importance of selecting the appropriate imaging plane in order to avoid hardware distortion of slice select gradients, emphasizes the importance of selecting frequency encoding gradient axes in order to orientate the long axis of the artefact away from the tissue of interest and, finally, compares the marked susceptibility artefact observed adjacent to hardware using gradient-echo with the artefact reduction achieved by using fast spin-echo sequences.

Artifacts↗

PubMed1997

Intranasal midazolam in patients with status epilepticus.

The patient in status epilepticus presents many challenges to the emergency physician. IV access is frequently difficult to achieve, and prolonged attempts at access can jeopardize the patient and endanger the caregiver. We present two cases in which the administration of intranasal midazolam appeared to successfully terminate status epilepticus. No adverse effects were noted. Studies are needed to clarify the safety, optimal dosing, and clinical utility of this treatment modality.

Administration, Intranasal↗

PubMed1997

Single and double autotransplants for relapsing/refractory Hodgkin's disease: results of two consecutive trials.

To evaluate a strategy of one cycle of dose-intensive chemotherapy for patients with Hodgkin's disease in sensitive relapse and two cycles for those with refractory disease, 122 patients received dose-intensive chemotherapy followed by autotransplant in two consecutive studies. Patients with refractory disease were offered a second transplant with different conditioning in the absence of progression or excessive toxicity. CR was present after treatment in 46% while 16% died in the peritransplant period. Of 41 patients with primary refractory disease and 42 with refractory relapse, 24 and 21 respectively received a second cycle. Of these 45 refractory patients, 12 were in CR and 11 in PR after the first cycle and 10 of these 11 in PR achieved a durable CR with the second transplant. The CR rate is 37% in patients with refractory relapse and 19% in those with primary refractory disease. At a median follow-up of 4 years, median survival is 45 months. Progression-free survival of the refractory patients who could receive a second cycle was similar to that of patients with sensitive disease. A sequential transplant strategy is feasible. A subgroup of patients with refractory disease can achieve long-term survival after sequential BMT.

Adolescent↗

PubMed1997

Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients.

Velo-cardio-facial syndrome (VCFS) is a relatively common developmental disorder characterized by craniofacial anomalies and conotruncal heart defects. Many VCFS patients have hemizygous deletions for a part of 22q11, suggesting that haploinsufficiency in this region is responsible for its etiology. Because most cases of VCFS are sporadic, portions of 22q11 may be prone to rearrangement. To understand the molecular basis for chromosomal deletions, we defined the extent of the deletion, by genotyping 151 VCFS patients and performing haplotype analysis on 105, using 15 consecutive polymorphic markers in 22q11. We found that 83% had a deletion and >90% of these had a similar approximately 3 Mb deletion, suggesting that sequences flanking the common breakpoints are susceptible to rearrangement. We found no correlation between the presence or size of the deletion and the phenotype. To further define the chromosomal breakpoints among the VCFS patients, we developed somatic hybrid cell lines from a set of VCFS patients. An 11-kb resolution physical map of a 1,080-kb region that includes deletion breakpoints was constructed, incorporating genes and expressed sequence tags (ESTs) isolated by the hybridization selection method. The ordered markers were used to examine the two separated copies of chromosome 22 in the somatic hybrid cell lines. In some cases, we were able to map the chromosome breakpoints within a single cosmid. A 480-kb critical region for VCFS has been delineated, including the genes for GSCL, CTP, CLTD, HIRA, and TMVCF, as well as a number of novel ordered ESTs.

Abnormalities, Multiple↗

PubMed1997

Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders.

Velo-cardio-facial syndrome (VCFS) is characterized by conotruncal cardiac defects, cleft palate, learning disabilities, and characteristic facial appearance and is associated with hemizygous deletions within 22q11. A newly recognized clinical feature is the presence of psychiatric illness in children and adults with VCFS. To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, we evaluated 26 VCFS patients by clinical and molecular biological methods. The VCFS children and adolescents were found to share a set of psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients, >18 years of age, were affected with bipolar spectrum disorders. Four of six adult patients had psychotic symptoms manifested as paranoid and grandiose delusions. Loss-of-heterozygosity analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and two did not have a detectable deletion. Somatic cell hybrids were developed from the two patients who did not have a detectable deletion within 22q11 and were analyzed with a large number of sequence tagged sites. A deletion was not detected among the two patients at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggest a common genetic etiology.

Abnormalities, Multiple↗

PubMed1996

Evaluation of fluvastatin in the treatment of hypercholesterolemia in renal transplant recipients taking cyclosporine.

Occlusive atherosclerosis is a major cause of morbidity and mortality in renal transplant recipients. Hyperlipidemia associated with the transplanted state may be at least partially responsible for this complication and is therefore an important target of therapy. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are powerful cholesterol-lowering drugs, but their broad use in transplant recipients has been hindered by concerns about interactions with cyclosporine. Cyclosporine interferes with the elimination of these agents, increasing their plasma and tissue levels and predisposing the patient to rhabdomyolysis. Fluvastatin, the first entirely synthetic HMG-CoA reductase inhibitor, possesses a distinct pharmacologic profile, including a shorter half-life and virtually no active circulating metabolites. Therefore, it may interact differently with cyclosporine. The pharmacokinetics and safety of fluvastatin, 20 mg/day, were evaluated in 20 hypercholesterolemic renal transplant recipients also receiving cyclosporine, usually in combination with azathioprine and methylprednisolone, during the 14-week study. Fluvastatin area under the curve, maximum plasma concentration, and time to maximum plasma concentration were minimally increased in these patients, unlike findings reported for lovastatin, pravastatin, and simvastatin. This suggests that metabolism of fluvastatin may be less affected by cyclosporine than that of other reductase inhibitors. Fluvastatin was well tolerated, with no evidence of myopathy, rhabdomyolysis, or ophthalmologic abnormalities. These findings and the significant reductions in total cholesterol and low-density lipoprotein cholesterol levels and the ratio of low-density to high-density lipoproteins achieved in these patients support the broader use of fluvastatin to treat hypercholesterolemia in renal transplant recipients.

Adult↗

PubMed1996

Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome.

Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated with typical facial appearance, cleft palate, cardiac defects, and learning disabilities. The majority of patients have an interstitial deletion on chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric illnesses have been reported in patients with VCFS, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric manifestations of VCFS could be due to haploin-sufficiency of a gene(s) within 22q11. One candidate that has been mapped to this region is catechol-O-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine-->methionine substitution at amino acid 158 of the membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4-fold reduction in enzymatic activity, compared with homozygotes for COMT158val. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158met, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form.

Abnormalities, Multiple↗

PubMed1996

PCR cloning and expression analysis of a cDNA encoding a pectinacetylesterase from Vigna radiata L.

A cDNA clone encoding a pectinacetylesterase (PAE) was isolated from 3-day-old mung bean seedlings using PCR-based techniques. Degenerate oligonucleotide primers were designed according to the N-terminus and internal peptides from the purified PAE. The full-length clone of 1453 bp codes for a signal peptide of 24 amino acids and a mature protein of 375 amino acids. The Mr and the pI of the cDNA-deduced amino acid sequence agree with the values estimated for the purified enzyme. No significant sequence identity between the PAE and any known protein could be found in the databases. Northern analysis revealed developmentally regulated expression of the mRNA in mung been seedlings.

Amino Acid Sequence↗

PubMed1996

Clustered genes within the genome of Arabidopsis thaliana encoding pectin methylesterase-like enzymes.

We focused our attention on the isolation and regulation of genes encoding for pectin methylesterase (PME) isoenzymes in Arabidopsis thaliana (At). The present data reports the identification of two PME-like genes, named AtPME1 and AtPME2, that are closely linked in the At genome. These genes possess different structural organisations. While all higher plant PME characterised so far possess an intron at a similar location relative to their coding sequence, AtPME2 shows an additional intron whose presence within other higher plant PME-like genes has not been previously reported. Sequence comparison of the N-terminal region suggests that the secretory pathways of the putative AtPME1 and AtPME2 isoforms are different, and that this region may contribute to specify a biological function to each isoform. Moreover, phylogenetic analysis reflects the possible existence of functional groups of PME isoforms in higher plant species that seem to have been conserved during evolution.

Amino Acid Sequence↗

PubMed1996

Pectinmethylesterase isoforms from Vigna radiata hypocotyl cell walls: kinetic properties and molecular cloning of a cDNA encoding the most alkaline isoform.

Peptide maps and partial amino acid sequences of the 3 main pectinmethylesterases (PMEs) solubilized from mung bean hypocotyl cell walls demonstrated that these proteins were different isozymes originating from a small multigene family. A cDNA clone encoding the most alkaline PME (PE gamma) have been obtained by PCR using degenerate oligonucleotide primers. Combining the protein and nucleotide sequencing data, the complete amino acid sequence of PE gamma was determined. The nature protein is composed of 318 amino acids with a calculated Mtau of 34 677 and an estimated pI of 9.84 consistent with the values previously obtained by SDS-PAGE and IEF. It shares most of the conserved regions of previously known PMEs. Enzymatic activities of the three isoforms were differently affected by the presence of cations in the incubation medium but, in all cases, infra-optimal cation concentrations induced two opposite effects: a decrease in the Vmax and an increase in the affinity of the enzymes for their substrate. The presence of cations in the assay modulates both the number of enzyme molecules available to the demethylation reaction and the conformation of the pectin and, in turn, the affinity of the PMEs for their substrate.

Amino Acid Sequence↗

PubMed1996

Gender differences and factors associated with the receipt of thrombolytic therapy in patients with acute myocardial infarction: a community-wide perspective.

In spite of national interest in gender differences in the presentation and management of chronic disease, limited information is available about possible gender differences in the receipt of thrombolytic therapy after acute myocardial infarction (AMI). As part of an ongoing community-based study of AMI, we examined gender differences in the receipt of thrombolytic therapy among 2885 patients with confirmed AMI. The study sample consisted of 1680 males and 1205 females with validated AMI who were admitted to 16 hospitals in the Worcester, Massachusetts, metropolitan area in four study periods between 1986 and 1991. During the years under study, 24.4% of men and 14.4% of women received thrombolytic therapy. Increases over time in the use of thrombolytic therapy were seen in both men (13.9% in 1986; 31.6% in 1991) and women (3.2% in 1986; and 19.0% in 1991). After controlling for a variety of factors that might affect use of thrombolytic agents, younger age, absence of a history of either congestive heart failure or stroke, and experiencing a Q-wave AMI were associated with receipt of thrombolytic therapy in both men and women; having an anterior AMI also was associated with use of thrombolytic agents in men. Women without as compared with those with a history of angina pectoris were significantly more likely to receive thrombolytics. Men who had Medicare insurance were significantly less likely to receive thrombolytics than were men with other types of health insurance. When this analysis was restricted to patients who were seen in area-wide hospitals within 6 hours of the onset of symptoms suggestive of AMI, similar factors were associated with the receipt of thrombolytic agents in men and women. The results of this community-wide study suggest a marked increase over the 5-year study period in the use of thrombolytic therapy in both men and women, with a greater relative increase observed in women. A relatively similar profile of patients likely to receive thrombolytic therapy was seen in both men and women.

Age Factors↗

PubMed1996

Isolation of a new clathrin heavy chain gene with muscle-specific expression from the region commonly deleted in velo-cardio-facial syndrome.

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are developmental disorders characterized by a spectrum of phenotypes including velopharyngeal insufficiency, conotruncal heart defects and facial dysmorphology among others. Eighty to eighty-five percent of VCFS/DGS patients are hemizygous for a portion of chromosome 22. It is likely that the genes encoded by this region play a role in the etiology of the phenotypes associated with the disorders. Using a cDNA selection protocol, we isolated a novel clathrin heavy chain cDNA (CLTD) from the VCFS/DGS minimally deleted interval. The cDNA encodes a protein of 1638 amino acids. CLTD shares significant homology, but is not identical to the ubiquitously expressed clathrin heavy chain gene. The CLTD gene also shows a unique pattern of expression, having its maximal level of expression in skeletal muscle. Velopharyngeal insufficiency and muscle weakness are common features of VCFS patients. Based on the location and expression pattern of CLTD, we suggest hemizygosity at this locus may play a role in the etiology of one of the VCFS-associated phenotypes.

Abnormalities, Multiple↗

PubMed1996

Burnout and its correlates in emergency physicians: four years' experience with a wellness booth.

OBJECTIVE: To measure the degree of burnout among emergency physicians (EPs) and to identify and rank predictive factors. METHODS: Using the Maslach Burnout Inventory as well as a 79-item questionnaire, a cross-sectional survey was conducted for physician registrants at the Annual Scientific Assemblies of the American College of Emergency Physicians from 1992 to 1995. Degrees of burnout were stratified into low, moderate, and high ranges. Univariate and stepwise multiple regression analyses were conducted to identify and rank correlates to burnout scores. RESULTS: Of 1,272 registrants taking the inventory, 60% registered in the moderate to high burnout ranges. Twenty-one correlates were identified. These were classified broadly in terms of negative perceptions of self, negative practice habits and attitudes, and unhealthy lifestyles. The most highly ranked correlates were: self-recognition of burnout, lack of job involvement, negative self-assessment of productivity, dissatisfaction with career, sleep disturbances, increased number of shifts per month, dissatisfaction with specialty services, intent to leave the practice within 10 years, higher levels of alcohol consumption, and lower levels of exercise. Age and years of practice were not significant predictors of burnout. Projected attrition rates were 7.5% over 5 years and 25% over 10 years. CONCLUSIONS: Elevated levels of burnout exist among a substantial percentage of surveyed EPs. However, there is evidence for a "survivor" category of practitioners for whom burnout either does not develop or is a reversible process. The projected attrition rate over 5 and 10 years appears to be no greater than that of the average medical specialty.

Adaptation, Psychological↗

PubMed1996

Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder?

OBJECTIVE: The purpose of this study was to conduct a systematic assessment of psychiatric illness in patients diagnosed with velo-cardio-facial syndrome, a genetic syndrome that involves over 40 somatic anomalies, learning disabilities, and behavioral disorders and is associated with a microdeletion on chromosome 22q11. METHOD: Subjects were referred for psychiatric diagnostic evaluation without regard to age or previous psychiatric history. In order to establish DSM-III-R consensus clinical diagnoses for patients who ranged in age from 5 to 34 years, the Diagnostic Interview for Children and Adolescents--Revised or the Structured Clinical Interview for DSM-III-R (SCID) was used. A review of available medical and psychiatric records and a clinical interview performed by two research psychiatrists to validate specific symptoms and syndromes reported in the Diagnostic Interview for Children and Adolescents--Revised and the SCID were used to elucidate the chronological appearance and duration of symptoms. RESULTS: Sixty-four percent (N = 16 of 25) of this unselected series of patients with velo-cardio-facial syndrome met DSM-III-R criteria for a spectrum of bipolar disorders with full syndromal onset in late childhood or early adolescence (mean age at onset = 12 years, SD = 3). In addition, 20% (N = 5) met DSM-III-R criteria for attention deficit hyperactivity disorder (ADHD), while 16% (N = 4) met criteria for attention deficit disorder without hyperactivity. In contrast to previous reports of a high prevalence of schizophrenia, none of the patients was diagnosed with schizophrenia, and only four had psychotic symptoms during a phase of their illness, all in their 20s or 30s. CONCLUSIONS: Given that the prevalence of bipolar disorder in the general population is estimated to be 1.5% and that the average age at onset is 24, these findings support an unusually strong association between velo-cardio-facial syndrome and early-onset bipolar disorder and suggest that a gene deleted at the 22q11 chromosomal locus may be involved in its pathogenesis. If confirmed, these findings may provide a new and fruitful line of investigation into the molecular basis of bipolar spectrum disorders.

Abnormalities, Multiple↗

PubMed1996

Treatment Effect of Niaspan, a Controlled-release Niacin, in Patients With Hypercholesterolemia: A Placebo-controlled Trial.

BACKGROUND: The present study was designed to determine the efficacy and safety of Niaspan (Kos Pharmaceuticals, Inc, Hollywood, FL), a new controlled-release formulation of niacin, in the treatment of primary hyperlipidemia, the occurrence and severity of flushing events, and potential adverse effects, particularly hepatotoxicity. METHODS AND RESULTS: The study was conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel comparison of Niaspan in doses of 1000 mg/day and 2000 mg/day, administered once a day at bedtime. One hundred twenty-two patients with low-density lipoprotein cholesterol levels >4.14 mM/L (160 mg/dL) with dietary intervention and high-density lipoprotein cholesterol </=1.81 mM/L (70 mg/dL) were randomized to one of three treatment groups: placebo, and 1000 mg/day or 2000 mg/day of Niaspan. Safety and efficacy measures included 12-hour serum fasting lipid and lipoprotein concentrations, serum analyte levels for major organ function, flushing diaries, and adverse event records. The placebo group demonstrated no significant changes in serum lipoprotein concentrations over the treatment period of 12 weeks, except for a slight 4% increase in high-density lipoprotein cholesterol. Niaspan significantly lowered low-density lipoprotein cholesterol levels by 6% and 14% for the 1000 mg/day and 2000 mg/day doses, respectively. High-density lipoprotein cholesterol levels rose significantly, with a 17% increase occurring at the 1000 mg/day dose and a 23% increase occurring at the 2000 mg/day doses, respectively. High-density lipoprotein cholesterol levels rose significantly, with a 17% increase occurring at the 1000 mg/day dose and a 23% increase occurring at the 2000 mg/day dose. Niaspan (2000 mg/day) produced significant decreases of 27% and 29%, respectively, for serum lipoprotein(a) and triglyceride concentration. Although the incidence of flushing was significant, these episodes were generally well tolerated. CONCLUSION: Niaspan administered in doses of 1000 mg/day and 2000 mg/day at bedtime were well tolerated with few side effects and produced favorable effects on the major circulating lipoproteins of patients with primary dyslipidemias as specified by the enrollment criteria.

Journal Article↗

PubMed1996

FGFR2 exon IIIa and IIIc mutations in Crouzon, Jackson-Weiss, and Pfeiffer syndromes: evidence for missense changes, insertions, and a deletion due to alternative RNA splicing.

Fibroblast growth factor receptor 2 (FGFR2) mutations have been associated with the craniosynostotic conditions Crouzon, Jackson-Weiss, and Pfeiffer syndromes. Previously, mutations were described in the exons IIIa and IIIc, which form the extracellular, third immunoglobulin-like domain (IgIII) and adjacent linker regions, both of which are normally involved in ligand binding. For all three conditions, mutations were found in exon IIIc. Only in Crouzon syndrome were mutations identified in exon IIIa. In this study, 39 cases with one of these three conditions were screened for exon IIIa or IIIc mutations. Eleven mutations are reported in 17 unrelated cases. Mutations in exon IIIa are identified for not only Crouzon but also Jackson-Weiss and Pfeiffer syndromes. Four mutations in either exon IIIa or exon IIIc reported only in Crouzon syndrome are present also in one of the other two syndromes. Two insertions, one in exon IIIa in a Crouzon syndrome patient and the other in exon IIIc in a Pfeiffer syndrome patient, were observed. The latter mutation has the same alternative RNA splicing effect as a reported synonymous mutation for Crouzon syndrome. A missense mutation was detected in one Pfeiffer syndrome family in which two members had craniosynostosis without limb anomalies. The inter- and intrafamilial variability in expression of FGFR2 mutations suggests that these three syndromes, presumed to be clinically distinct, are instead representative of a spectrum of related craniosynostotic and digital disorders.

Acrocephalosyndactylia↗