Rare dental abnormalities seen in oculo-facio-cardio-dental (OFCD) syndrome: three new cases and review of nine patients.

Oculo-facio-cardio-dental syndrome is a very rare condition. So far, only nine cases have been documented. We report on three additional female patients representing the same entity. The clinical findings were: congenital cataract, microphthalmia/microcornea, secondary glaucoma, vision impairment, ptosis, long narrow face, high nasal bridge, broad nasal tip with separated cartilages, long philtrum, cleft palate, atrial septal defect, ventricular septal defect, and skeletal anomalies. The following dental abnormalities were found: radiculomegaly, delayed dentition, oligodontia, root dilacerations (extension), and malocclusion. For the first time, fusion of teeth and hyperdontia of permanent upper teeth were seen. In addition, structural and morphological dental changes were noted. These findings expand the clinical spectrum of the syndrome.

Severe mental retardation and macroorchidism without mutation in the FMR1 gene.

Only one missense mutation, an Ile304Asn, has been reported in the fragile X gene (FMR1). This mutation is located in the second KH domain of FMR1, and has led to the discovery of the function of the FMR1 gene product as an RNA-binding protein. The patient carrying this mutation has profound mental retardation, macroorchidism, and an "acromegalic" face with prominent supraorbital ridges, enlarged jaw, heavy brow ridges, thick lips, and a broad nose. We have studied the possible involvement of FMR1 in two maternal half-brothers with a phenotype similar to that of the patient with the Ile304Asn mutation. Both brothers had an identical number of CGG repeats in the normal size-range, and shared the same maternal Xq27 haplotype. Southern blot analysis with two overlapping FMR1 cDNA clones, spanning the total FMR1 open reading frame, showed no major deletions, insertions, or gross rearrangements. Single-strand conformation pattern (SSCP) analysis of the KH domains showed no aberrant patterns. The total open reading frame of the FMR1 gene was cloned and sequenced, but no mutation was found. Northern blot analysis showed mRNA in the normal size-range, and immunocytochemistry on individual lymphocytes indicated that FMRP, the protein product of FMR1, was present. In conclusion, it is unlikely that FMR1 plays a role in the phenotype of this patient. Other genes may be responsible for the combination of mental retardation and macroorchidism.

The secretor locus as a marker for prenatal prediction of myotonic dystrophy (DM).

To verify the reliability of secretor status for prenatal diagnosis of myotonic dystrophy (DM), 179 amniotic fluid samples were compared with saliva or urine samples of the infants by hemagglutination inhibition. While no discrepancies were observed, problems could arise with intermediate results. Additionally, secretor typing is only informative in 8.4% of patients.

Wolf-Hirschhorn syndrome: case report and review of the chromosomal aberrations associated with diaphragmatic defects.

A female fetus showing severe growth retardation was delivered at 31 weeks of gestation because of fetal distress. At birth, the infant showed bradycardia and no spontaneous breathing. Although high frequency oscillatory ventilation was started, severe asphyxia persisted and the infant died of respiratory insufficiency. At the autopsy, the propositus showed microcephaly, prominent glabella, broad bridge of the nose, ocular hypertelorism, poorly differentiated and low-set ears, bilateral palatoschisis, and micrognathia. Midline closure defects of the cervical spine bodies, lower jaw, and skull base were seen at postmortem radiography. An extreme hypoplasia of both lungs, a large defect of the left diaphragm with upward displacement of viscera, and multiple cortical cysts in both kidneys were seen at postmortem examination. Karyotyping revealed a chromosomal imbalance with 46, XX, del(4) (pter-->13), characterizing the Wolf-Hirschhorn syndrome. Because diaphragmatic defects can occur in association with specific recognizable patterns of human malformation careful pathologic and genetic workup of all affected infants in crucial for accurate genetic counseling.

Maternal uniparental disomy 7--review and further delineation of the phenotype.

UNLABELLED: Uniparental disomy (UPD) is defined as the inheritance of both homologous chromosomes from only one parent. So far, maternal UPD 7 has been described in 28 cases. Here, we report 4 new cases, present clinical information of 5 cases previously reported by us, and review the clinical and molecular findings of all 32 cases. We found a phenotype characterized by pre- and postnatal growth retardation, occipitofrontal head circumference in the lower normal range, a triangular face, and retarded bone maturation. Findings of the facial gestalt included a high and broad forehead and a pointed chin. A broad mouth with down-turned corners, prominent ears, café-au-lait spots, hemihypotrophy, or clinodactyly were rarely present. Psychomotor development was delayed in 6 cases. The clinical findings strikingly resemble the phenotype of the heterogeneous Silver-Russell syndrome (SRS). Other anomalies were less frequently found than in SRS. Molecular investigations revealed 11 cases with isodisomy and 17 cases with heterodisomy. In 4 cases this information was not available. From the allelic distribution of the microsatellites investigated, 9 cases might be the consequence of an error at maternal meiosis I, and 6 cases might be due to non-disjunction at maternal meiosis II. Three of the 17 heterodisomic cases had trisomy 7 in chorionic villi, in the remaining cases no prenatal diagnosis through chorionic villus sampling was reported. CONCLUSION: Maternal UPD 7 should investigated in children with pre- and postnatal growth retardation anda facial gestalt characterized by a high and broad forehead and a pointed chin, as well as in cofined placental mosaicism for trisomy 7.