Alveolar capillary dysplasia with multiple congenital anomalies and bronchoscopic airway abnormalities.

Alveolar capillary dysplasia is a rare and fatal disease of newborn infants. Here we describe a patient with alveolar capillary dysplasia, multiple congenital anomalies, a novel genetic mutation and previously undocumented airway findings on bronchoscopy. Knowledge of these associations may help diagnose this rare disorder in neonates with hypoxemic respiratory failure.

Retrospective diagnosis of chondrodysplasia punctata.

The diagnosis of punctate epiphyseal dysplasia (PED) after disappearance of puncta is problematical. In some instances, however, the phenotypic and radiographic characteristics may persist and permit a retrospective diagnosis of PED in persons with unclassified bone dysplasia or bone changes of unknown origin. We report a boy aged 8 years who presented with unusual bony abnormalities that were consistent with a diagnosis of PED.

Chondrodysplasia punctata in siblings and maternal lupus erythematosus.

Chondrodysplasia punctata (CDP) was diagnosed clinically and radiographically in a male child born in Cape Town in 1991. His only sibling, a brother born in 2000 was similarly but more severely affected. The boys' mother had longstanding disseminated lupus erythematosus and epilepsy, for which she had been treated with chloraquine and other therapeutic agents during both pregnancies. The parents were non-consanguineous, and the family history was unremarkable. In addition to these affected brothers, seven previous instances of the association of CDP and maternal lupus erythematosus (MLE) have been reported. On this basis, MLE must be regarded as yet another causative factor in CDP.

Split hand foot malformation is associated with a reduced level of Dactylin gene expression.

Split hand foot malformation (SHFM) is a congenital limb malformation presenting with a median cleft of the hand and/or foot, syndactyly and polydactyly. SHFM is genetically heterogeneous with four loci mapped to date. Murine Dactylaplasia (Dac) is phenotypically similar, and it has been mapped to a syntenic region of 10q24, where SHFM3 has been localized. Structural alterations of the gene-encoding dactylin, a constituent of the ubiquitinization pathway, leading to reduced levels of transcript have been identified in Dac. Here, we report a significant decrease of Dactylin transcript in several individuals affected by SHFM. This observation supports a central role for dactylin in the pathogenesis of SHFM.

Developmental absence of the premolar teeth: dental management.

A boy aged 11 years presented with dental pain, several carious teeth and a localized area of acute necrotizing ulcerative gingivitis (ANUG). Developmental absence of the premolar teeth was notable and additional anomalies included mid-facial hypoplasia, mandibular prognathism, transposed teeth and delayed exfoliation of the deciduous teeth. These abnormalities have significant oral, dental, orthodontic and orthognathic implications.

Distal limb malformations: underlying mechanisms and clinical associations.

Congenital malformations of the extremities are conspicuous and have been described through the ages. Over the past decade, a wealth of knowledge has been generated regarding the genetic regulation of limb development and the underlying molecular mechanisms. Recent studies have identified several of the signaling molecules, growth factors, and transcriptional regulators involved in the initiation and maintenance of the apical ectodermal ridge (AER) as well as the molecular markers defining the three axes of the developing limb. Studies of abnormal murine phenotypes have uncovered the role played by genes such as p63 and Dactylin in the maintenance of AER activity. These phenotypes resemble human malformations and in this review we describe the underlying mechanisms and clinical associations of split hand/foot malformation and ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome, which have both been associated with mutations in the p63 gene.

Tibial aplasia--VACTERL association, a new syndrome?

We report on a male infant, born to nonconsanguineous parents, with a vertebral anomaly, cardiac defect, tracheo-oesophageal fistula and hypospadias (VACTERL association) together with bilateral tibial aplasia. This pattern of abnormalities appears to represent a unique syndrome.

Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27.

Split-hand/split-foot malformation (SHFM), a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals, is phenotypically analogous to the naturally occurring murine Dactylaplasia mutant (Dac). Results of recent studies have shown that, in heterozygous Dac embryos, the central segment of the apical ectodermal ridge (AER) degenerates, leaving the anterior and posterior segments intact; this finding suggests that localized failure of ridge maintenance activity is the fundamental developmental defect in Dac and, by inference, in SHFM. Results of gene-targeting studies have demonstrated that p63, a homologue of the cell-cycle regulator TP53, plays a critically important role in regulation of the formation and differentiation of the AER. Two missense mutations, 724A-->G, which predicts amino acid substitution K194E, and 982T-->C, which predicts amino acid substitution R280C, were identified in exons 5 and 7, respectively, of the p63 gene in two families with SHFM. Two additional mutations (279R-->H and 304R-->Q) were identified in families with EEC (ectrodactyly, ectodermal dysplasia, and facial cleft) syndrome. All four mutations are found in exons that fall within the DNA-binding domain of p63. The two amino acids mutated in the families with SHFM appear to be primarily involved in maintenance of the overall structure of the domain, in contrast to the p63 mutations responsible for EEC syndrome, which reside in amino acid residues that directly interact with the DNA.

Primary reservoirs of Streptococcus mutans and their relationship to caries experience in adults with good oral hygiene.

Primary reservoirs of Streptococcus mutans were identified in a group of 21 adults with intact dentitions and good oral hygiene by obtaining multiple plaque samples from all available tooth surfaces. Routine cultural methods and a rapid plate scoring method employing a 7-point ordinal scale were used to assess S. mutans levels. Oral hygiene status (DI-S) and caries experience (DMFT and DMFS) were determined clinically. Primary S. mutans reservoirs (high scores) were restricted essentially to the posterior interproximal areas and occasionally in the occlusal pits and fissures of partially erupted mandibular third molars. An anterior to posterior gradient of increasing S. mutans scores was observed for interproximal sites. Oral hygiene scores correlated poorly with DMFT, DMFS and the S. mutans scores obtained for different anatomic locations.

Prenatal gastric dilatation and infantile hypertrophic pyloric stenosis.

Fetal sonography showed persistent gastric dilatation with no other abnormalities. Following uneventful pregnancy and delivery, the patient presented with typical clinical and radiologic features of infantile hypertrophic pyloric stenosis. Literature review indicates that this association was never reported.

Longitudinal ultrasonic biometry of various parameters in fetuses with abnormal growth rate.

The growth rate of various organs and parameters was evaluated by ultrasound examination in one group of small-for-gestational age (SGA) and another group of large-for-gestational age (LGA) fetuses. Three different patterns of growth were selected in the SGA group and two different types of growth acceleration were observed in the LGA group. On the basis of these results, it has been concluded that the type of intra-uterine growth retardation or acceleration is dependent more on the time at which the insult which brings it on, appears, and less on the specific etiological factor.

Mastocytemia in dogs with acute inflammatory diseases.

Nineteen dogs were identified that had mastocytemia (mast cells in venous blood samples) not associated with mast cell neoplasia. The first 10 dogs were identified by examination of blood films from dogs with suspected parvovirus enteritis (8), fibrinous pericarditis and pleuritis secondary to thoracic lacerations (1), and renal insufficiency of unknown cause (1). Because of the apparent association with acute enteritis, blood films from 52 suspected canine parvovirus cases were examined retrospectively and 8 mastocytemic dogs were found. An additional 52 canine blood films were randomly selected from the same retrospective time period and 1 mastocytemic dog was found that had pneumothorax, pelvic fractures, and hemorrhagic septic abdominal effusion secondary to renal hemorrhage and traumatized intestines. All mastocytemic dogs had acute inflammatory leukograms the day that mast cells were first detected: neutropenia with toxic neutrophils (4), neutropenia with a left shift (8), total neutrophil count within reference interval but with a left shift (5), or neutrophilia with a left shift (2). All dogs except the renal insufficiency case had circulating toxic neutrophils. Five dogs were mastocytemic on more than 1 day. The pathogenesis of the mastocytemia associated with the acute inflammatory disease was not determined.