Packed red cell transfusion does not compromise chromosome analysis in newborns.

PURPOSE: Critically ill neonates are frequently transfused with packed red cells. Some of these transfused neonates also need chromosome analysis. There is a long-standing tradition in pediatrics of not performing chromosome analysis after transfusion. We wished to determine whether transfusion with packed red cells affect the cytogenetic results in neonates. METHOD: The medical records of all neonates at the Medical College of Georgia who had had chromosome analysis between June 1995 and June 1998 were reviewed. Ten neonates had received transfusion prior to cytogenetic testing. Of these 10 infants, two had been transfused two or more times. Routine cytogenetic analysis of 20 metaphases at 550-band level had been performed on all 10 patients. Heteromorphic markers were compared in 10 randomly selected metaphases for any discrepancy. To determine whether there were theoretical reasons to delay chromosome analysis in transfused neonates, samples of irradiated, and/or filtered, and nonfiltered blood were obtained from the blood bank and analyzed for the presence of lymphocytes. RESULTS: Prior transfusion did not affect karyotype results. A nonmosaic abnormal karyotype was found in 3 of the 10 patients. A fourth patient's karyotype was 45,X/47,XXX. This mosaicism was constitutive and consistent as demonstrated by a follow-up chromosome analysis. All other abnormal karyotypes were consistent with the dysmorphic phenotype. Randomly selected metaphases did not show any differences in the identifiable heteromorphic markers in all 10 patients. Although there was a 50% chance of patients receiving blood from a donor of opposite sex, there were no instances in which cells with a karyotype of the opposite sex were found in the patients' blood. The irradiated and filtered cultured donor blood samples did not show any metaphases. However, metaphases were seen in the cultures from nonfiltered and nonirradiated donor blood. CONCLUSIONS: Based on these results one does not need to delay karyotyping babies who have had blood transfusions. Packed red cell transfusion in newborns does not compromise the accuracy of chromosome analysis in our study even with multiple transfusions.

Prenatal diagnosis of a trisomy 17p derived from a de novo non-mosaic satellited marker.

A trisomy 17pter --> p11.2 derived from a supernumerary de novo satellited marker was identified by GTG bands and fluorescent in situ hybridisation (FISH) in amniocytes of a fetus with malformations and intrauterine growth retardation (IUGR). At 39 weeks a male infant with a phenotype similar to other postnatal cases of 'pure' complete trisomy 17p was born. Some additional clinical features, however, make him more severely affected than previous patients.

Facial dysmorphologic and skeletal cephalometric findings associated with conotruncal cardiac anomalies. off.

Anomalous conotruncal cardiac morphology and facial dysmorphology have been associated with neural crest-pharyngeal arch abnormalities. To assess these associations, 20 patients 3 to 18 years old with tetralogy of Fallot (TOF) or persistent truncus arteriosus (PTA) were evaluated by cardiologic, facial dysmorphic, and cephalometric criteria. The average number of facial abnormalities of neural crest derivation was two, while pharyngeal arch derivative abnormalities were observed with an average of five defects per subject. The total group had many more facial malformations than normal populations (P less than .00001). The occurrence of defects was not significantly different between TOF and PTA patients. Thirteen TOF patients 8 years, 9 months to 18 years, 10 months old (x = 13 years, 4 months) had lateral cephalograms analyzed for skeletal relationships. The TOF patients exhibited higher than usual distribution of dolichofacial growth patterns (6 of 13), Class II skeletal relationships (6 of 13), mandibular retrusion (7 of 13), and maxillary protrusion (6 of 13). Trends were not absolute, since opposite patterns were individually expressed, and referencing by race tended to show more normal values for respective groups.

Association of pigmentary anomalies with chromosomal and genetic mosaicism and chimerism.

We have evaluated eight patients with pigmentary anomalies reminiscent of incontinentia pigmenti or hypomelanosis of Ito. All demonstrated abnormal lymphocyte karyotypes with chromosomal mosaicism in lymphocytes and/or skin fibroblasts. In seven the skin was darkly pigmented, and in all of these seven cases the abnormal pigmentation followed Blaschko lines. The literature contains at least 36 similar examples of an association between pigmentary anomalies and chromosomal mosaicism, as well as five examples of an association with chimerism. The pigmentary anomalies are pleomorphic, and the chromosomal anomalies involve autosomes and sex chromosomes. The pigmentation patterns are reminiscent of the archetypal paradigm seen in allophenic mice and demonstrate the clonal origin of melanoblasts from neural crest precursors. Patients with anomalous skin pigmentation, particularly when it follows a pattern of Blaschko lines, should be appropriately evaluated for a possible association with chromosomal or genetic mosaicism or chimerism.

Hypertrichosis cubiti.

Hypertrichosis is an unusual but well-recognized genetic condition. Hypertrichosis may be generalized or limited to specific body areas, in which case it is usually not associated with other anomalies. Five previous cases of hypertrichosis cubiti have been reported, with short stature in 2 sibs being the only other associated abnormalities. We report on a child with hairy elbows, developmental delay, facial asymmetry, and delayed speech with normal parents. Our patient may represent severe expression of the hairy elbow syndrome or constitute a previously unrecognized syndrome.

Syndrome of imperforate oropharynx with costovertebral and auricular anomalies.

This is the second report of a syndromic form of imperforate oropharynx associated with costovertebral and auricular anomalies.

Joubert syndrome: early diagnosis by recognition of the behavioral phenotype and confirmation by cranial sonography.

Our experience with two children with Joubert syndrome demonstrates how the diagnosis, if suspected by recognition of the behavioral phenotype, can rapidly be made by employing cranial sonography. This technique also may afford prenatal diagnosis of the syndrome in future siblings of confirmed cases. We have produced an educational videotape demonstrating the dynamic behavior of these patients. It is our hope that increased familiarity with the behavior phenotype through this report and through distribution of the videotape will lead to early and accurate diagnosis of further cases of this syndrome.

Ring chromosome 5.

A case of an infant with ring chromosome 5 is presented. The phenotype of this patient and other reported cases is analyzed with respect to the deletion of the long arm of chromosome 5.

Verification of the fetal valproate syndrome phenotype.

We have evaluated 19 children who were exposed to valproic acid (VPA) in utero to look for manifestations of a fetal valproate syndrome (FVS), as proposed by Di Liberti et al. [1984]. We found no consistent alterations of pre- or postnatal growth with exposure to VPA monotherapy. Postnatal growth deficiency and microcephaly were present however, in two thirds of children exposed to VPA in combination with other anticonvulsants. Developmental delay or neurologic abnormality was found in 71% of those exposed to VPA monotherapy, and in 90% of those exposed to VPA and other anticonvulsants. Craniofacial anomalies, which can be seen with other anticonvulsant exposures, including midface hypoplasia, short nose with a broad and/or flat bridge, epicanthal folds, minor abnormalities of the ear, philtrum or lip, and micrognathia were also found in infants whose mothers used VPA. Prominent metopic ridge and outer orbital ridge deficiency or bifrontal narrowing and certain major anomalies such as tracheomalacia, talipes equinovarus (with intact spine) and lumbosacral meningomyelocele seem to be peculiar to infants with VPA exposure. Other defects such as urogenital anomalies, inguinal or umbilical hernias, and minor digital anomalies that are common to other prenatal anticonvulsant exposures are also occasionally found in those exposed to VPA. Heart defects have been found in infants exposed to nearly every class of anticonvulsant although the types of defects associated with maternal VPA use may be clarified when classified by pathogenetic mechanism. Our findings overall are in agreement with the report of Di Liberti et al. [1984].

The possible role of homeotic genes in the causation of malformations in monozygotic twins.

It is proposed that the malformations observed to occur with increased frequency in monozygotic twins are similar to the types of malformations caused by mutation in homeotic genes in animals.

Association of low blood manganese concentrations with epilepsy.

A comparison of hospitalized epileptic patients with matched normals showed that the mean whole blood manganese (Mn) concentration of the epileptic population was significantly lower than the mean of the normal population. The whole blood Mn concentration in the epileptics did not correlate either with seizure frequency or with anticonvulsant therapy. It was observed, however, that patients whose epilepsy was a result of trauma had significantly higher blood Mn concentrations than patients whose history was negative for trauma.

Craniofrontonasal dysplasia: clinical and genetic analysis.

We have identified a case of craniofrontonasal dysplasia which demonstrates the potential lethality of this gene. Genetic analysis of this pedigree and nine others reveals that craniofrontonasal dysplasia does not follow a Mendelian mode of inheritance and may be a human mutation analogous to the T-locus of mice.