American Journal of Medical Genetics 139A:131–135 (2005) Clinical Report Perlman Syndrome: Clinical Report and Nine-Year Follow-Up Maria Piccione, 1 Massimiliano Cecconi, 2 Mario Giuffre `, 1 Margherita Lo Curto, 1 Michela Malacarne, 2 Ettore Piro, 1 Andrea Riccio, 3 and Giovanni Corsello 1 * 1 U.O. Pediatria e Terapia Intensiva Neonatale, Dipartimento Materno Infantile, Universita`degli Studi di Palermo, Italy 2 Laboratorio di Genetica Umana E.O. Ospedali Galliera di Genova, Italy 3 Dipartimento di Scienze Ambientali Seconda Universita`degli Studi di Napoli, Italy We present the clinical and follow-up data of a female infant with Perlman syndrome from birth to the age of 9 years. Main features of Perlman syndrome include polyhydramnios, fetal over- growth, neonatal macrosomia, macrocephaly, dysmorphic facial features, visceromegaly, nephroblastomatosis, and a predisposition for Wilm’s tumor. In our patient, the nephromegaly with nephroblastomatosis was not present at birth or during the neonatal period; it became evident in the first months of postnatal life. A Wilm’s tumor was diagnosed when she was about 1 year old. Long term follow-up documents the natural history of Perlman syndrome and allows us to establish the long-term prognosis of the affected individuals. ß 2005 Wiley-Liss, Inc. KEY WORDS: Perlman syndrome; fetal over- growth; nephroblastomatosis; Wilm’s tumor INTRODUCTION The Perlman syndrome is a rare disorder whose main features are polyhydramnios, fetal overgrowth, neonatal macrosomia, macrocephaly, dysmorphic facial features, vis- ceromegaly, nephroblastomatosis, and a significant predis- position for Wilm’s tumor, occurring at a very young age [Herman and McAlister, 1995]. The characteristic features were first described by Liban and Kozenitzsky [1970] in two siblings of a consanguineous Yemenite Jewish family. Perlman et al. [1973, 1975, 1986], described five affected sibs. Moreover, Neri et al. [1984] delineated the syndrome on a family with two affected children. Fourteen additional cases of Perlman syndrome were subsequently documented by Greenberg et al. [1986, 1988], Hamel et al. [1989], Chernos et al. [1990], Grundy et al. [1992], Herman and McAlister [1995], Coppin et al. [1997], Fahmy et al. [1998], Henneveld et al. [1999], Schilke et al. [2000], and five cases have been described with prenatal ultrasound [van der Stege et al., 1998, Chitty et al., 1998, and DeRoche et al., 2004]. The prognosis is severe with neonatal death in most children [Henneveld et al., 1999]; only four cases have previously been described with a survival beyond the first year of life, patient 2 reported by Neri et al. [1984]; Greenberg et al. [1986]; patient 1 described by Grundy et al. [1992]; patient 1 described by Fahmy et al. [1998]. Clinical overlap with other overgrowth syndromes associated with Wilm’s tumor has been discussed by other authors [Schilke et al., 2000]. The genetic basis of the Perlman syndrome is unknown and confirmatory tests are not available. The diagnosis is based on comprehensive phenotypic analysis and confirmed by histological renal evidence [Schilke et al., 2000]. Although both sexes are affected, the sex ratio is 2M:1F [Cohen et al., 2002]. The syndrome has been described in both consanguineous and nonconsanguineous parents [Chitty et al., 1998]. Inheri- tance is autosomal-recessive [Henneveld et al., 1999]. The karyotype is normal in all studied patients, except for the case of Chernos et al. [1990], with a ‘‘de novo’’ extra G-positive band on the tip of the short arm of chromosome 11. We present the clinical and follow-up data of a female infant with Perlman syndrome from birth to the age of 9 years. CLINICAL REPORT This female infant was the first child of nonconsanguineous healthy parents (the mother was 29-year-old and the father was 30 at the time of the child’s birth). She was born after 40 weeks of gestation by Cesarean because of polyhydramnios and fetal distress. The mother reported no exposure to teratogens, alcohol, or tobacco during pregnancy. At birth, the infant weighed 3,950 g (>90th centile ) with a length of 51 cm (50th centile) and occipitofrontal circumference (OFC) 38.5 cm (>97th centile). Neonatal evaluation revealed macrocephaly with multiple facial anomalies, prominent forehead, full round face, deeply set eyes, hypertelorism, epicanthic folds, broad flat nasal bridge, anteverted upper lip, highly arched palate, dysplastic ears. A 2/6 Levine systolic murmur, normal abdominal organs, and axial hypotonia were also found. Cerebral sonogram study showed a regular thin-walled ovoid cystic formation (26 mm  7 mm) well delimited near the left lateral ventricle. Abdominal sonogram showed normal liver, spleen, and kidneys. A muscular ventricular septal defect was found at echocardiography. A high-resolution cytogenetic analysis of peripheral blood lymphocytes showed normal female chromosomes 46,XX. At 6 months of age, the infant had mild hepatosplenomegaly and nephromegaly. Abdominal sonogram (Fig. 1) showed bilaterally enlarged kidneys (Ø 9 cm) with decreased sub- capsular echogenicity and with loss of corticomedullary differentiation, initially interpreted as infantile polycystic kidneys. *Correspondence to: Prof. Giovanni Corsello, Universita ` di Palermo, Dipartimento Materno Infantile, Via Cardinale Rampolla, 1, Palermo, Italy 90142. E-mail: giovanni.corsello@unipa.it Received 8 June 2005; Accepted 22 August 2005 DOI 10.1002/ajmg.a.30994 ß 2005 Wiley-Liss, Inc.