Late sequelae of aberrant intrauterine bands

LETTERS

TO T H E E D I T O R

Clinical notes

"Clinical Notes" represent clinical and/or laboratory experiences which can be presented in 200 to 400 words, 3 or 4 references, and, if contributory, one illustration or short table. "Clinical Notes" are subject to the same critical peer review and editing as papers published in other sections of the JOURNAL.

Late sequelae of aberrant intrauterine bands To the Editor: Seven infants with a constellation of anomalies secondary to aberrant tissue bands were described by Jones and associates in the January, 1974, issue of THE JOURNAL.1 Four of the infants survived the newborn period. In addition to a similarly affected infant born at our institution in June, 1973, we have recently seen two adults with this pattern of anomalies. Both were referred by the plastic surgery service for genetic counseling. They were leading normal adult lives although neither has married nor had children. CASE REPORTS

Case 1. J. C. is a 24-year-old white male born at term to a 26year-old primigravida after a reportedly normal pregnancy.

Multiple anomalies were noted at birth including a left cleft lip with wide palatal cleft, brachysyndactyly with symphalangism involving all four extremities, and distal peripheral edema of the right lower extremity secondary to a constrictive band. Examination at 24 years revealed a repaired left cleft lip, hypoplasia of the left malar region, left palpebral fissure and iris smaller than right, aplasia of the sternal head of the pectoralis major, and the prominent limb anomalies. These were typical of a combination of congenital amputations and distal fusions ("pseudosyndactyly"). Surgical scars were present above the right ankle, but we were unable to determine the nature of the original condition. Multiple surgical procedures have been performed. Six siblings were unaffected. Case 2. J. S., 39-year-old white male bacteriology student, is severely affected (Fig. 1). He was born at home after a 32 weeks' gestation. Birth weight was 2 pounds; his mother was a 15-year-old p r i m i g r a v i d a w h o s e p r e g n a n c y had b e e n unremarkable. His grandmother assisted at the delivery and reported "bands wrapped around him." Abnormalities similar to those in the patients of Jones and associatesI included a skull

Fig. 1. Case 2. Surgical scars about the right eye, nose, and lip are obvious. Also note the maxillary hypoplasia, more marked on the right, the right eyelid deficiencies, and low position of the right orbit.

Vol. 85, No. 3, pp. 434-445

Volume 85 Number 3

Letters to the Editor

defect in the right parieto-occipital area with an atrichotic, nodular soft tissue protrusion, marked maxillary hypoplasia, absent right lower eyelid with ocular asymmetry, broad cleft nose, right cleft of the lip and palate, and bilateral hand anomalies consisting of congenital amputations, symphalangism, and distal pseudosyndactyly, and a right clubfood. Numerous surgical procedures have been performed beginning at 2 weeks of age. Intelligence is normal, and functioning is handicapped only by his unusual appearance. Three siblings have no anomalies. DISCUSSION We think that these two men represent less severely affected cases with the same disorder as reported by Jones and associa t e s ) The purpose of this letter is to emphasize that intelligence can be unaffected and that a lack of other major system malformations makes survival and normal productivity possible. The absence of affected family members is in keeping with previous data. 1 Claire O. Leonard, M.D. Vincent M. Riccardi, M.D. Departments o f Biophysics, Genetics, and Pediatrics University of Colorado Medical Center Denver, Colo. 80220

REFERENCE 1.

Jones, K. L., Smith, D. W., Hall, B. D., Hall, J. G., Ebbin, A. J., Massound, H., and Golbus, M. S.: A pattern of craniofacial and limb defect secondary to aberrant tissue bands, J. PEDIATR. 84: 90, 1974.

Fetal hemoglobin and the irreversibly sickled cell in sickle cell disease To the Editor: In sickle cell anemia it is usual for a percentage of the erythrocytes to exist as permanently deformed, irreversibly sickled cells (ISC). Indications are that the disc to sickle to disc transformation may be accompanied by the loss of microspherules leading to permanent cell deformation. 1 Electron microscopic evaluations of the ISC have shown changes consistent with the interpretation that the membrane of these erythrocytes have suffered structural damage3 Fetal and adult sickle hemoglobin are heterogeneously distributed in the red cells of sickle cell anemia, and there is evidence that cells with the lowest synthesis of fetal hemoglobin are destined to become irreversibly sickled cells. 3 Further reports indicate variable propensity for sickling of red blood cells in the same environment. ! Reprint address:Michael K. MeCormack, DightInstitute.for Human Genetics, Universityof Minnesota, Minneapolis,Minn. 55455.

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Our sample consisted of 54 multiplex families (two or more affected full sibs per family) collected by Dr. Graham Serjeant of Jamaica, West Indies. Fetal hemoglobin values were estimated by the alkali denaturation technique of Betke and associates. 4 Irreversible sickle cell counts were estimated as described by Serjeant and associates. 5 Fetal hemoglobin values and irreversible sickle cell percentages were estimated on 54 sets of full sibs (two or three sibs per family). To assess the degree of familial determination of fetal hemoglobin and ISC counts in sickle cell anemia, an analysis of variance was performed using the 54 sets of full sibs. For fetal hemoglobin, the observed F statistic (F = 1.59; 53, 65df; P (0.05) indicated a significant intraclass correlation coefficient whereas for the ISC counts, the F statistic (F = 1.27; 53, 66 df; P > 0.05) indicated a nonsignificant intraclass correlation coefficient. Thus familial factors (either genetic or environmental) appear to have some influence on the level of fetal hemoglobin in sickle cell anemia. The observed intraclass correlation coefficient for fetal hemoglobin was 0.198. Even though there was no significant intraclass correlation of the ISC count, a highly statistically significant negative correlation was observed between fetal hemoglobin levels and ISC counts (r = -0.38, P (0.01). Similar distributions of elevated fetal hemoglobin levels have been reported in girls across all ages and boys 14 years and younger. A lower incidence of elevated fetal hemoglobin levels, however, was found in boys 15 years and older.6 In our study the previously reported. 6 However, while Bicker 5 group reported 26% (5 of 19) of the boys 15 years and older with elevated fetal hemoglobin levels, we found 71.5% (35 of 49) of the boys in this same age group to have elevated fetal hemoglobin values, differing significantly from Bickers' data (X 2 = 11.50, 1 df, P (0,025). However, we confirm a statistically significant difference between the sexes in the proportions of individuals 15 years and older with elevated fetal hemoglobin values (X 2 = 6.08, 1 df, P (0.025). These data suggest three major points: (1) that some familial factor or factors are influencing the net synthesis of fetal hemoglobin in sickle cell anemia; (2) the statistically significant negative correlation coefficient between the fetal hemoglobin levels and the ISC counts indicates that fetal hemoglobin may definitely influence the formation of the irreversibly sickled cell in sickle cell anemia; and (3) further investigation is necessary to discern if real sex differences do exist for elevated fetal hemoglobin values. Michael K. McCormack Victor L. Bresson Dight Institute for Human Genetics University o f Minnesota Minneapolis, Minn. 55455 Graham R. Serjeant M R C Epidemiology Unit University of the West Indies Mona, Kingston Jamaica, West Indies