American Journal of Medical Genetics 56184-187 (1995) Familial Inverted Duplication 7p G. Bradley Schaefer, Kelli Novak, David Steele, Bruce Buehler, Shelley Smith, Dianna Zaleski, Diane Pickering, Marilu Nelson, and Warren Sanger zyxwv Hattie B. Munroe Center for Human Genetics, Meyer Rehabilitation Institute, University of Nebraska Medical School, Omaha. Nebraska A 10-month-oldfemale with developmental delay and failure to thrive was referred for genetic evaluation as part of an adoption as- sessment. Physical exam showed a mildly beaked nose and clinodactyly, but otherwise nothing remarkable. Chromosome analysis showed an inverted duplication of the p12.2-pl3 portion of chromosome 7[(46, XX, dup(7)(p13p12.2)1. The proposita’s older brother, mother, and grandmother were cognitively delayed and had the same chro- mosome 7 duplication. A review of the liter- ature showed no other cases involving this exact duplication. o 1995 Wiley-Liss, Inc. KEY WORDS: chromosome 7, inverted duplication,partial trisomy 7 INTRODUCTION zyxwvu Fewer than 30 cases of duplication of 7p have been documented in the last 20 years. These have been asso- ciated with variable clinical manifestations. Smaller duplications involving only the 7p12.2+p13 region have not been reported. This report suggests that this particular duplication is associated with mild to mod- erate mental retardation and growth delay without other significant clinical manifestations. CASE REPORT The proposita (Fig. 1) was the fourth child born of a 28-year-old mother; the father was 30 years old and unrelated to the mother. The child was thought to be delivered 1 month premature, although the dating of conception was in question. She weighed 2,895 g at birth, and there were no complications in the newborn period. She was referred for genetic evaluation at age 9 months by her pediatrician for “failure to thrive.” At that time she had been in foster care for 4 months because it was felt that it would be difficult for the bio- logical mother to care for her, and there were concerns for poor weight gain. However, she had only gained 2 pounds since foster placement despite concerted efforts to feed her, including nasogastric feedings. Physical examination at age 9 months showed that she was small for chronological age, and her motor mile- stones were about 3 months behind. She had a slightly beaked nose and bilateral fifth finger clinodactyly. There were no other significant physical findings. Subsequently, a gastrostomy tube was placed because of continued difficulties with feeding and poor weight gain. By 20 months of age, there had been sig- nificant “catch-~p’~ growth, with height of 81 cm (2550%)and a weight of 9.9 kg (25%).She has contin- ued to have global developmental delays, however, especially prominent in speech production. The family history (Fig. 2) includes one maternal half sister (111-4) and a full brother (111-2) who are neuro- developmentally normal and have normal growth para- meters. A 2-year-old full brother (111-3) is delayed in speech, has a history of “balance problems,” and has glandular hypospadias with ventral penile chordee. No other dysmorphic features were noted; growth parame- ters are within normal limits. All of the children are in foster care. Their mother (11-1) has a full-scale z I& (WISC-R) of 65 and has a legal guardian. She has nor- mal craniofacial features and no congenital anomalies or dysmorphic features. She graduated from high school in a Special Education Program. She has a brother and a sister (11-4 and 11-51 who were not exam- ined, but social work records refer to them as “slow.” The maternal grandmother (1-2) was examined and was not dysmorphic, but did appear to be at a func- tional level similar to that of her daughter. Because of the family history and a pending adop- tion, chromosomal analysis was requested to “rule out fragile X syndrome (per adoption agency referral).” zy ~~~ Received for publication April 28, 1994; revision received September 30,1994. Address reprint requests to Warren G. Sanger, Ph.D., Univer- sity of Nebraska Medical Center, 600 So. 42nd St., Omaha, NE zyxwvu 0 1995 Wiley-Liss, Inc. 68198-5440. MATERIALS AND METHODS Fragile X testing was performed by culturing lym- phocytes from a peripheral blood sample utilizing three