Additional manifestations of the Neu-Laxova syndrome.

A newborn female with intrauterine growth retardation, bilateral cleft lip and palate, absent external nares and eyelids, low set ears, short contracted limbs, webbed digits, intestinal malrotation, and unilateral renal agenesis is reported. These multiple malformations are considered part of the Neu-Laxova syndrome.

Genetic and clinical studies in 13 patients with the Wolf-Hirschhorn syndrome [del(4p)].

Clinical and cytogenetic studies are reported on 13 patients with Wolf-Hirschhorn syndrome. The oldest of the living twelve probands is 24 years of age. Three of these patients had a translocation involving the short arm of chromosome 4, and in one of these the anomalous chromosome was inherited from the father. Another three patients were believed, on the basis of GTG-staining, to have a translocation although the origin of the translocated chromatin could not be identified. In the remaining seven patients the anomalous chromosome appeared to be a simple deletion, although in two cases a translocation could not be ruled out. Cytogenetic studies in these patients suggest that the critical deletion involved in Wolf-Hirschhorn syndrome is within 4p16.

Deficits in space-form perception in patients with sex chromosome mosaicism (45,X/46,XY).

Several studies have shown that selective deficits in space-form perception are found in patients with Turner's syndrome, associated with 45,X or a structural anomaly of an X chromosome. The authors sought to determine whether significant deviations from normal or from Turner's syndrome (relative to space perception) occur when a Y chromosome is present. The four patients studied, aged between 4 1/2 and 24 years, had a karyotype of 45,X/46,XY and a phenotype ranging from sexual ambiguity at birth to typical Turner's syndrome. Although all were in the normal intelligence range (IQ 80 or above), on testing they demonstrated below-average ability in tasks involving visualization of spatial forms, and their drawings were generally immature. The results suggest that patients with sex chromosome mosaicism X/XY may have similar deficits in space-form perception and orientation to those previously demonstrated in Turner's syndrome.

Familial systemic lupus erythematosus.

Pedigrees were obtained from 340 patients with systemic lupus erythematosus (SLE). Two hundred ten (62%) of the patients were from the wards of Lupus Clinic at the Los Angeles County-University of Southern California Medical Center, and 130 (38%) were from a private practice. Forty-one (12%) of the 340 patients with SLE had affected relatives: five had two and 36 had one affected relative. Ten (30%) of the 33 male patients and 31 (10%) of the 307 female patients had relatives with SLE. Examination of the individual pedigrees included examples of possible autosomal dominant, autosomal recessive, and sex-linked dominant and recessive inheritance. When all the pedigrees were considered as a group, multifactorial inheritance was suggested.

HLA phenotype frequencies in individuals with cleft lip and/or cleft palate.

The HLA types of 133 patients with cleft lip and/or cleft palate were determined. Caucasian patients with isolated cleft palate showed a possible association with HLA. Ten of 11 male patients had HLA--A2 as compared to one out of eight female patients (P less than 0.005). Caucasian males with cleft lip and cleft palate had a slight increased frequency of HLA--Aw24 (P = 0.07) and Mexican-American males with cleft lip and/or cleft palate showed an increase of antigen HLA-A28 (P = 0.07), though neither were statistically significant. Females with cleft lip and/or cleft palate from either racial group had no differences from the controls. The serum from 90 mothers of patients with cleft lip and/or cleft palate were reacted against their child's lymphocytes. Of these crossmatch tests, 12% were found to be positive. These preliminary results suggest that male patients with isolated cleft palate are worthy of further studies with respect of HLA associations.

Chromosomal anomalies in patients with retinoblastoma.

Karyotypes from 50 persons with retinoblastoma confirmed by histopathological examination were studied by conventional staining and Giemsa-banding techniques. Two chromosomal anomalies were found. An interstitial deletion of the long arm of No. 13 chromosome was identified by Giemsa-banding in the karyotypes from a boy with unilateral retinoblastoma. Another boy with unilateral tumor had a karyotype of 47,XXY. These findings provide additional evidence that a deletion of chromosome No. 13, most likely involving band 13q14, is associated with the development of retinoblastoma. In conjunction with other reports, our findings also suggest that retinoblastoma may be found more frequently in children with chromosomal aneuploidy.

Heterogeneity in the campomelic syndromes. Long-and short-bone varieties.

Analysis of 9 cases of bilateral bent limbs (campomelia) and dwarfism, as well as a review of the literature, indicate that campomelic syndrome appears to be a well-defined distinct disorder which the authors call long-limbed campomelic syndrome. Other neonates with congenital bent-limbed dwarfism can be classified as having short-limbed campomelic syndrome, and among these at least two distinct forms have been delineated--the craniosynostotic and the normocephalic form. Congenital bent bones also occur in a variety of generalized disorders of ossification that must be distinguished from these well-defined types of campomelic dwarfism.

Heterogeneity in the campomelic syndromes: long and short bone varieties.

There appears to be definite heterogeneity within the campomelic syndromes. We are broadly classifying these into the classic or long bone campomelic syndromes and 2 distinct short bone varieties designated as the normocephalic short-boned and craniosynostotic short-boned types, respectively (Table 1).

Aberrant tissue bands and craniofacial defects.

A report of 8 cases of craniofacial anomalies and aberrant tissue bands has been presented. Analyses of the pedigrees, pregnancy histories and chromosome analyses were unrevealing. This syndrome appears to be a sporadic disorder and it is important to delineate it further from other syndromes for which recurrence risks are known.

Sex chromosome mosaicism of X/XY or X/XY/XYY.

To date, we have studied 7 patients with X/XY mosaicism, one of whom showed an X/XY/XYY pattern. Four patients presented as newly born infants because of incomplete male development, ambiguity of external genitalia or Turner syndrome. The other 3 patients presented in midchildhood or early adult life. Bilateral gonadectomy, histologic examination of the gonads for tumor or testicular tissue, and chromosome analysis from blood and gonad specimens (and usually skin) were done in these 7 patients. The Y cell line and mosaicism were always detected in the blood culture although the predominant cell line in the majority of tissues was 45,X. The Y chromosome in one of the patients failed to show the expected bright fluorescence over the long arm, and the Y chromosome of another patient previously reported had a terminal nonfluorescing portion of the long arm. Patients with masculinization showed normal height and, on laparotomy, mixed gonadal dysgenesis. Patients with Turner syndrome showed bilateral streak gonads (2) and, in one 2 1/2-year-old girl, a bilateral gonadoblastoma. All patients with Turner syndrome were less than the third percentile in height. All 7 patients were reared as female, 4 of them requiring surgery to diminish the size of the clitoris. All 7 patients appeared to be developing normally. Nonrecognition or delay of the diagnosis, which still occurs in this condition, appears to be a result of the mild physical abnormalities in some patients and a clinical diagnosis of Turner syndrome supported only by a negative X-chromatin result.

A pattern of craniofacial and limb defects secondary to aberrant tissue bands.

Seven infants have been studied who have a similar pattern of severe craniofacial and limb anomalies associated with aberrant tissue bands. The craniofacial anomalies consist of unusual encephaloceles, facial clefts, and cranial plus midfacial distortion; the limb anomalies consist of constrictions, amputations, and pseudosyndactyly. These defects are interpreted as being secondary to the early distorting and disruptive effects of aberrant tissue bands, the etiology for which is undetermined. Survival beyond the neonatal period has occurred in four of the five liveborn patients, indicating that early death should not necessarily be anticipated. Recurrence risk is apparently negligible.