American Journal of Medical Genetics 128A:294–298 (2004) Clinical Report Infant With Severe Penicillamine Embryopathy Born to a Woman With Wilson Disease R. Pinter, 1 * W.A. Hogge, 1 and E. McPherson 1,2 1 Department of Genetics, Magee-Women’s Hospital, Pittsburgh, Pennsylvania 2 Department of Pediatrics, Children’s Hospital Pittsburgh, Pittsburgh, Pennsylvania We report a chromosomally normal infant boy with congenital diffuse cutis laxa, severe micrognathia, contractures of all limbs, and central nervous system abnormalities including agenesis of the corpus callosum, born to a woman taking D-penicillamine (DP) for Wilson disease (WD) throughout her pregnancy. His postnatal course was remarkable for chronic lung disease, pro- found developmental delays, and probable cortical blindness, as well as resolution of his cutis laxa. Embryopathy is a rare com- plication in babies born to pregnant women treated with DP, and there have been only seven previous reports of birth defects in exposed infants (three of which had favor- able postnatal outcomes). The etiology of the severe outcome in this boy is unclear, but prenatal measurement of maternal cop- per and zinc levels may be indicated for management. ß 2004 Wiley-Liss, Inc. KEY WORDS: penicillamine embryopathy; cutis laxa; joint contrac- tures; arthrogryposis; corpus callosum agenesis; develop- mental delay; cortical blind- ness; Wilson disease INTRODUCTION Embryopathy is a rare complication in babies born to women being treated with D-penicillamine (DP). Numerous reports support the safety of prenatal use of DP in pregnancy. Roubenoff et al. [1988] summarized studies of a total of 40 women taking DP for Wilson disease (WD) during pregnancy who had 57 normal babies. Furthermore, they reviewed reports on 93 babies born to mothers exposed to various doses and durations of DP while pregnant, of whom only four had congeni- tal abnormalities. Of these four, two of the mothers had WD, and their babies had reversible cutis laxa and inguinal hernias. To date, there have been 10 reported cases of birth defects in DP-exposed babies. Three of these were not published but were submitted to the United States Food and Drug Administration (FDA) in 1966–1984 [Rosa, 1986]. Details of these cases are summarized in Table I. Continuing DP therapy in pregnant women with WD has been recommended because stopping therapy has led to clinical deterioration from renewed copper toxicity [Scheinberg and Sternlieb, 1975; Brewer et al., 2000], although Marecek and Graf [1976] offered an alter- native view. Untreated maternal WD has been associat- ed with infant hepatomegaly and a persistent hepatic enzyme elevation [Oga et al., 1993]. Of the five cases of congenital anomalies in DP-exposed infants from mothers with WD, only two had adverse outcomes (first-trimester viremia [Rosa, 1986] and maternal hypotension [Gal and Ravenel, 1984]), both of which might be explained by other complicating factors. It is generally accepted that DP is safe to give to pregnant women with WD. CLINICAL REPORT The propositus (Figs. 1–3) is a 16-month-old male born after 37 weeks gestation to a 35-year-old G2 P1 woman with WD, who was on DP throughout the preg- nancy. Vaginal delivery was induced because of oligohy- dramnios. She took 1 g/day DP for the first 20 weeks of gestation, but this was reduced to 500 mgm/day after her first fetal ultrasound at 16 weeks showed arthro- gryposis, bowed femurs, and a single umbilical artery. Amniotic fluid was normal then, but oligohydramnios developed prior to delivery. His amniocentesis karyo- type was 46XY. The pregnancy was otherwise uncom- plicated, with no other known maternal exposures. Maternal urine copper excretion was followed, but *Correspondence to: Robert Pinter, Department of Genetics, Magee-Womens Hospital, Pittsburgh, PA. E-mail: rpinter@mail.magee.edu Received 17 May 2002; Accepted 6 June 2002 DOI 10.1002/ajmg.a.10871 ß 2004 Wiley-Liss, Inc.