9 6 Clinical and laboratory observations The Journal of Pediatrics July 1990 Selective deficiency of antibody responses to polysaccharide antigens in a child mosaic for partial trisomy I (46,XX,dir dup (I) (q 2 q23)/46,XX) Emily L. Germain-Lee, MD, Gerald Schiffman, MD, Emilie H. Mules, ScM, and Howard M. Lederman, MD, PhD From the Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, the Department of Microbiology and Immunology, State University of New York Health Science Center at Brooklyn, New York, and the Genetics Laboratory, Kennedy Institute, Baltimore, Maryland The selective inability to mount antibody responses to polysaceharide antigens occurs infrequently and usually is seen in association with other defects of the immune system, such as IgG subclass deficiency, functional asplenia, and Wiskott-Aldrich syndrome. 1 This report describes a selec- tive deficiency of antipolysaccharide immunity in a child mosaic for partial trisomy 1. The association of these two extremely rare conditions in a single patient may suggest a role for a gene on chromosome 1 in the humoral immune response to polysaccharide antigens. CASE REPORT The patient, the 3100 gm product of a full-term gestation, was born to a 16-year-old black adolescent. The infant had multiple congenital anomalies, including Pierre Robin syndrome with cleft palate, scoliosis, bilateral rneatal hypoplasia of the ear canals, hy- pertrophic obstructive cardiomyopathy, Wolff-Parkinson-White syndrome, severe mental retardation, and cerebral palsy. Ophthal- mologic examination revealed myopia and astigmatism with nor- mal visual acuity. The patient had no cataracts, glaucoma, or ret- inal abnormalities. Auditory examination by evoked potentials revealed no response from the left ear and a mild conductive hear- ing deficit on the right. Cytogenetic analysis of lymphocyte cultures from the proband revealed two cell lines [46,XX, dir dup (1) (pter ~ q23::q12 q23::q23 ~ qter)/46,XX]. In the first cell line (39/50 = 78%) a direct duplication in the long arm of chromosome 1 was present, the duplicated segment being lq12 ~ lq23 (Figure). The second cell line (11/50 = 22%) had a normal 46,XX karyotype. The proband was thus mosaic for trisomy of the ql 2 --~ q23 portion of chromo- Supported in part by grants Nos. AI23023 and RR 05378 from the National Institutes of Health (Dr. Lederman) and by Core Grant No. HD 24061 from the National Institute of Child Health and Human Development Mental Retardation Research Center (Ms. Mules). Submitted for publication Oct. 9, 1989; accepted Jan. 29, 1990. Reprint requests: Howard M. Lederman, MD, PhD, Eudowood Division of Pediatric Immunology, CMSC 1103, Johns Hopkins Hospital, Baltimore, MD 21205. 9/22/19709 some 1. Cytogenetic studies of the proband's mother revealed a normal karyotype. The father was not available for analysis. When the patient was 4 days of age, midgut volvulus secondary to malrotation developed, and surgery was required. Subsequent surgical procedures included tracheostomy for airway manage- ment, gastrostomy tube placement for management of gastro- esophageal reflux and recurrent aspiration pneumonia, insertion of a ventriculoperitoneal shunt to control hydrocephalus, cleft palate repair, and tympanostomy tube placement for chronic otitis media. When the patient was 1 month of age, scleral ieterus developed in her mother, who was also found to have hepatitis B. The infant, who was symptom free, subsequently had positive test results for both hepatitis B surface antigen and e antigen; her antigen test results have remained persistently positive, but she has had only minimal elevations of liver enzymes. The child had episodes of pneumococcal bacteremia at ages 20 and 26 months, recurrent otitis media, and several episodes of Pseudomonas tracheitis. Immunizations were up-to-date, includ- ing the Haemophilus influenzae b vaccine (HibVax, from Con- naught Laboratories, Inc., Swiftwater, Pa.), which was given at age 24 months. The patient was treated with phenobarbital, phenytoin, and theophylline, as well as with metaproterenol and cromolyn so- dium administered by inhalation. She has continued to grow well, and her height and weight have remained within the normal range. The mother's family history was negative for miscarriages, early infant deaths, congenital anomalies, or unusual susceptibility to infection. The mother denied alcohol or drug exposure during pregnancy. The father's family history was unobtainable. The par- ents are unrelated, and the patient has no siblings. At age 36 months, the child became febrile and was brought to the hospital. There were coarse rhonchi throughout the lungs, but the physical examination findings were otherwise unchanged from baseline findings. The leukocyte count was 8900/mm 3 with 41% neutrophils, 45% lymphocytes, and 4% monocytes. The hemoglo- bin value was 14.0 gm/dl, the hematocrit 41.4%, and the platelet count 244,000/mm 3. Lumbar puncture revealed 33 leukocytes/ mm 3 with 73% polymorphonuclear cells, 99 erythrocytes/mm 3, glucose concentration 95 mg/dl (5.3 mmol/L), and protein con- centration 55 mg/dl. Cultures of blood were positive for Strepto- coccus pneumoniae, and counterimmunoelectrophoresis of eere- brospinal fluid was positive for S. pneumoniae antigen.