Interstitial and terminal deletions of the long arm of chromosome 4: further delineation of phenotypes.

We reviewed 45 patients with a deletion of the long arm of chromosome 4. Forty-one were previous reports (25 terminal deletions and 16 interstitial deletions) and 4 are new cases with terminal deletions. Of the 29 patients with terminal deletions, 18 with deletion at 4q31 and 4 at 4q32----qter had an identifiable phenotype consisting of abnormal skull shape, hypertelorism, cleft palate, apparently low-set abnormal pinnae, short nose with abnormal bridge, virtually pathognomonic pointed fifth finger and nail, congenital heart and genitourinary defects, moderate-severe mental retardation, poor postnatal growth, and hypotonia. Six patients with a deletion at 4q33 and one patient with deletion 4q34 were less severely affected. In general, patients with various interstitial deletions proximal to 4q31 had a phenotype that was less specific, although mental retardation and minor craniofacial anomalies were also present. There were 3 patients with piebaldism and one with Rieger syndrome. We conclude that terminal deletion of chromosome 4q (4q31----qter) appears to produce a distinctive malformation (MCA/MR) syndrome in which the phenotype correlates with the amount of chromosome material missing and which differs from the more variable phenotype associated with interstitial deletions of 4q.

Predicting in vitro tissue culture growth for cytogenetic evaluation of stillborn fetuses.

A prospective study was undertaken of 131 perinatal deaths to determine whether gestational age, body weight, maceration degree and autopsy interval influenced successful in vitro tissue culture for cytogenetic evaluation. Perinatal populations were categorized as neonatal death (NND), fresh stillbirth (FSB), or graded as macerated stillbirth (MAC-0, MAC-1, MAC-2, MAC-3). Metaphase production by at least 15 cells separated 'growth' from 'no growth' categories after sampling liver, kidney and spleen. Body weight and degree of maceration were predictive of successful 'growth', while gestational age and autopsy interval were not. Body weight was significant in separating 'growth' from 'no growth' in NND (P = 0.05), FSB, MAC-0 and MAC-1 (P = 0.01). Growth probabilities were 0.78 (NND), 0.57 (FSB), 0.49 (MAC-0), 0.38 (MAC-1) and zero for MAC-2 and MAC-3. We conclude that (a) tissues from MAC-2 and MAC-3 fetuses do not grow and thus need not be sampled at autopsy, (b) maceration degree and body weight can be used to predict the growth probability in the other categories, (c) tissue samples can be taken during daylight hours, since autopsy interval does not influence successful growth provided the fetus is refrigerated at 4 degrees C, (d) all of the above conclusions have cost-efficiency implications for cytogenetic laboratories.

Mosaicism or pseudomosaicism: the problem of hypermodal cells in amniotic fluid cell culture.

A series of 2029 consecutive amniotic fluid specimens studied for prenatal genetic diagnosis were reviewed and reassessed so as to evaluate the frequency and clinical significance of hypermodal cells in amniotic fluid cell cultures. Hypermodal cells were defined as those with more than 46 chromosomes, and were characterized by an additional structurally normal or structurally abnormal chromosome. Of 2029 specimens, 47 (2.31 per cent) contained a total of 167 hypermodal cells. True fetal mosaicism was detected in three cases (0.14 per cent). All had hypermodal cells in more than one culture flask or colony which contained the same aberrant chromosome complement. In all but one case the babies were normal when only one cell was hypermodal, or when several cells were hypermodal but present in only one colony or one culture vessel. One case had an extra No. 20 chromosome in one cell. Although the child had multiple anomalies, they were not characteristic of trisomy 20, and subsequent chromosomal study on the baby postnatally revealed a 46,XX karyotype. The in situ coverslip technique is recommended as the preferred method for prenatal diagnosis, and it is useful as an aid in differentiating true mosaicism from pseudomosaicism.