No abstract

Maternal uniparental disomy for the entire chromosome 7 has so far been reported in three patients with intrauterine and postnatal growth retardation. Two were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous, and one because he was homozygous for a rare COL1A2 mutation. We investigated 35 patients with either the Silver-Russeli syndrome or primordial growth retardation and their parents with PCR markers to search for uniparental disomy 7. Four of 35 patients were found to have maternal disomy, including three with isodisomy and one with heterodisomy. The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7. It is suggested to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardation.

A review of case reports on patients with ring chromosome revealed 30 individuals (plus two fetuses) who inherited the ring from a total of 23 carrier parents (21 mothers and 2 fathers). The proportion of cases with inherited rings, among all patients with a ring, was calculated to be 5.6% as an upper limit. However, because of a propable difference in survival and fertility between individuals with transmitted and do novo rings, and because of the preferential publication of cases involving inherited rings (and thus a publication bias), the proportion of inherited rings should in reality be no more than 1%. Out of 30 transmitted rings, there were 9 where parent and child were both mosaics, suggesting an inherited instability of the chromosome involved leading to de novo re-formation of the ring in the second generation. The relatively mild clinical manifestations of ring chromosomes, in general, was found to be even more striking in familial cases. In half of the offspring the phenotype was very similar to that of the parent. However, in about a third of cases the offspring were more severely (mentally) affected. This fact should be considered in genetic counseling of clinically normal women who carry a ring chromosome.

An international group of clinicians working in the field of dysmorphology has initiated the standardization of terms used to describe human morphology. The goals are to standardize these terms and reach consensus regarding their definitions. In this way, we will increase the utility of descriptions of the human phenotype and facilitate reliable comparisons of findings among patients. Discussions with other workers in dysmorphology and related fields, such as developmental biology and molecular genetics, will become more precise. Here we introduce the anatomy of the nose and philtrum, and define and illustrate the terms that describe the major characteristics of these body regions.

Body measurements were taken and the prevalence of major malformations and of 57 minor anomalies was determined in 106 children with malignant disease, in 81 of their sibs, and in 106 control subjects matched to the patients according to sex, age and ethnic origin. Leukaemic children had a significantly smaller head circumference than the corresponding control children, but no significant differences in height, weight, anthropometric and syndromologic indices were found. No differences were observed in the frequency of associated major malformations including renal malformations detectable by sonography. The prevalence of minor anomalies was significantly higher in the patients with malignant disease and their sibs than in the control children: 69.2% of the patients, 63.0% of the sibs and 34.6% of the control subjects had at least one minor anomaly. When two and more minor anomalies were considered, the prevalence figures were 36.5%, 29.6% and 12.5%, respectively. Among the single minor anomalies only the Sydney line was significantly more frequent in patients with solid tumours. No specific association of an individual dysplasia or a pattern of minor anomalies with a given tumour could be established.

No abstract

In two non-consanguineous Hungarian Roma (Gypsy) children who presented with cardiomyopathy and decreased plasma carnitine levels, we identified homozygous deletion of 17081C of the SLC22A5 gene that results in a frameshift at R282D and leads ultimately to a premature stop codon (V295X) in the OCTN2 carnitine transporter. Carnitine treatment resulted in dramatic improvement of the cardiac symptoms, echocardiographic, and EKG findings in both cases. Family investigations revealed four sudden deaths, two of them corresponded to the classic SIDS phenotype. In postmortem tissue specimens available from three of them we could verify the homozygous mutation. In liver tissue reserved from two patients lipid droplet vacuolization could be observed; the lipid vacuoles were located mainly in the peripherolobular regions of the acini. In the heart tissue signs of generalized hypertrophy and lipid vacuoles were seen predominantly in the subendocardial areas in both cases; some aggregates of smaller lipid vacuoles were separated, apparently by membranes. Review of all OCTN2 deficiency cases reported so far revealed that this is the first presentation of histopathology in classic familial sudden infant death syndrome (SIDS) with an established SLC22A5 mutation. In addition to the two affected homozygous cardiomyopathic children and three homozygous sudden death patients, the genetic analysis in 25 relatives showed 14 carriers. The mutant gene derived from five non-consanguineous grandparents, each of them having 6-14 brothers and sisters. This alone suggests a wide ancestral spread of the mutation in certain Roma subpopulations.

A 2-year-old girl presented with thrombocytopenic purpura. Clinical examination and follow-up documented severe bone marrow hypoplasia associated with bilateral progressive Coats retinopathy, nail dystrophy, fine hair, and apparent chromosome instability. The syndrome is regarded as a variant of the Révész syndrome sharing some findings of dyskeratosis congenita.