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Cancer Prone Disease Section Mini Review Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Cancer Prone Disease Section Mini Review Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism) Maria Piccione, Giovanni Corsello Dipartimento Materno-Infantile University of Palermo, Palermo, Italy Published in Atlas Database: December 2006 Online updated version: http://AtlasGeneticsOncology.org/Kprones/PerlmanID10117.html DOI: 10.4267/2042/38420 This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence. © 2007 Atlas of Genetics and Cytogenetics in Oncology and Haematology Etiology: The genetic basis of the Perlman syndrome is Identity unknown and there is no conclusive laboratory test to Note: The Perlman syndrome is characterized by confirm the diagnosis. Although both sexes are polyhydramnios, fetal overgrowth, neonatal affected, the sex ratio is 2M:1F. The diagnosis is based macrosomia, high neonatal mortality, macrocephaly, on characteristic features and confirmed by histological dysmorphic facial features, visceromegaly, renal evidence. The syndrome has been described in nephroblastomatosis and a predisposition for Wilms both consanguineous and non-consanguineous tumor at very early age. couplings. Inheritance: Inheritance is of an autosomal recessive nature. Figure 1,2 : Macrocephaly, hypertelorism, epicanthus, broad flat nasal bridge, anteverted upper lip, axial hypotonia. Atlas Genet Cytogenet Oncol Haematol. 2007;11(2) 136 Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism) Piccione M, Corsello G Figure 3 : Abdominal ultrasound scan at 6 months of age: nephromegaly with lobulated contoured kidneys and loss of corticomedullary differentiation. - Cardiomegaly. Clinics - Congenital heart disease: interrupted aortic arch and Phenotype and clinics anomalous coronary vessels and the dextroposition of the heart, muscular ventricular septal defect. Abnormalities: - Intestinal malformations: intestinal malrotation and - Growth: oversize already evident in the prenatal and distal ileal atresia and volvulus and intestinal postnatal period. malrotation with caecum located on the midline, while - Craniofacial: macrocephaly, prominent forehead, most of the small intestine was located on the right. deep-set eyes, hypertelorism, epicantal folds, broad flat - Hemangiomas: Capillary hemangioma in the left nasal bridge, everted upper lip, high arched palate, low- antecubital fossa, choroids plexus hemangioma and set ears (figure 1,2). superficial cutaneus capillary hemangioma around the - Visceral: nephromegaly, nephroblastomatosis, Wilms umbilicus. tumor (figure 3). - Cryptorchidism. - Occasional abnormalities (table 1): - Skeletal abnormalities: the absence of the normal - Central nervous system abnormalities: agenesis of the widening of the lumbar interpediculate distances, corpus callosum; large cisterna magna; retrocerebellar rounded iliac wings, small sacrosciatic notches in a and perichiasmatic leptomeningeal cysts, white matter patient, and in patients showing crowded toes and hypoplasia and grey matter heterotopia involving the bilateral calcaneovalgus deformity, genua recurvata, cerebellum and superior colliculi; choroid plexus left metatarsus varus, right hallux varus, severe right hemangiomas; generalized cerebral atrophy with a convex dorsal and left convex lumbar scoliosis, lumbar marked deficit in the myelinization of the white matter; left periventricular ovoid cystic formation. Atlas Genet Cytogenet Oncol Haematol. 2007;11(2) 137 Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism) Piccione M, Corsello G hyperlordosis and crest iliac asymmetry, prominent Histopathologic findings show cytodifferentiated xiphisternum. nodular renal blastema and nests of immature glomeruli - Hypotonia. together with sclerotic glomeruli and primitive - Developmental delay. structures. Foci of hamartomatous tissue can be found Prenatal diagnosis is possible for families at risk for in the medulla. Perlman syndrome. The fetal overgrowth and Nephroblastomatosis predisposes to the development of particularly the OFC greater than the 90th centile for Wilms tumor, which is frequent and has been found in gestational age, that is associated with polyhydramnios, 7 of the 23 reported patients. Renal biopsy is necessary may be the first signs of Perlman syndrome. A prompt to evaluate the presence of Wilms tumor. Wilms tumor recognition and an accurate follow-up are was diagnosed at the ages of 4 days, 8 months, 10 recommended to offer these patients clinical assistance months, 10 months, 4 years and 6 months and 1 year and to prevent the high morbidity and mortality in and 8 months of age. Perlman syndrome. Organomegaly is frequent (cardiomegaly, Differential diagnosis nephromegaly and hepato/splenomegaly). In the few patients who survived beyond neonatal age, It is a clinical overlap with other overgrowth a psychomotor delay of various degree was reported. A syndromes associated with Wilms tumor. Wilms tumor 12 year old girl is referred was moderately retarded, is also associated with Beckwith-Wiedemann partly due to chemotherapy and radiation; a 1-year-old syndrome, Sotos syndrome, Weaver syndrome and patient had a development quotient (DQ) of 50, a nine- Simpson-Golabi-Behemel syndrome (table 2). year-old patient had a normal cognitive level and the Evolution neurological examination was normal. Pre and postnatal nephromegaly is evident. In a lot of Prognosis the cases described neonatal nephromegaly is present at The prognosis is severe with neonatal death in most birth. In a patient, the neonatal nephromegaly is not children; only 5 cases have been described with a evaluated and a patient described at birth had not survival beyond the first year of life. organomegaly. Nephromegaly is associated with fetal lobulation. Nephroblastomatosis is characteristic. Table 1 : Characteristic clinical features of Perlman syndrome Atlas Genet Cytogenet Oncol Haematol. 2007;11(2) 138 Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism) Piccione M, Corsello G Table 2: Comparison of Perlman, Beckwith-Wiedemann, Sotos, Weaver and Simpson-Golabi-Behmel syndromes. Hamel BCJ, Mannens M., Bokkerink JPM. Perlman syndrome: Cytogenetics report of a case and results of molecular studies. Am J Hum Genet 1989;45 (suppl.):A48. (Abstract). No chromosomal abnormalities have been found thus Chernos JE, Fowlow SB, Cox DM. A case of Perlman far, except for the case of Chernos et al, with a ‘de syndrome associated with a cytogenetic abnormality of novo’ extraG-positive band on the tip of the short arm chromosome 11. Am J Hum Genet 1990;47 (suppl.)A28. of chromosome 11. (Abstract). Grundy RG, Pritchard J, Baraitser M, Risdon A, Robards M. Perlman and Wiedemann-Beckwith syndromes: two distinct References conditions associated with Wilms tumour. Eur J pediatr Liban E, Kozenitzsky Il. Metanephric hamartomas and 1992;151:895-898. nephoblastomatosis in siblings. Cancer 1970;25:885-888. Herman TE, McAlister WH. Perlman syndrome: report of a Perlman M, Goldberg GM, Bar-Ziv J, Danovitch G. Renal case with additional radiographic findings. Pediatr Radiol hamartomas and nephroblastomatosis with fetal gigantism:a 1995;25:S70-S72. familial syndrome. J Pediatr 1973;83:414-418. Coppin B, Moore I, Hatchwell E. Extending the overlap of three Perlman M, Levin M, Witels B. Syndrome of fetal gigantism, congenital overgrowth syndromes. Clin Genet 1997;51:375- renal hamartomas and nephroblastomatosis with Wilms¹ 378. tumor. Cancer 1975;35:1212-1217. Chitty LS, Clark T, Maxwell D. Perlman syndrome: a cause of Neri G, Martini-Neri ME, Katz Ben E, Optiz JM. The Perlman enlarged, hyperechogenic kidneys. Prenat Diagn Syndrome of Familial Renal Dysplasia with Wilms tumor, fetal 1998;18:1163-1168. gigantism and multiple congenital anomalies. American Journal Fahmy J, Kaminsky C, Parisi MT. Perlman syndrome: a case of Medical Genetics 1984;19:195-207. report emphasizing the similarity to and distinction from Beckwith-Wiedemann and prune-belly syndromes. Pediatr Perlman M. Perlman syndrome: familial renal dysplasia with radiol 1998;28:179-182. Wilms tumor, fetal gigantism and multiple congenital anomalies. Am J Med Genet 1986;25:793-795. Van der Stege JG, van Eyck J, Arabin B. Prenatal ultrasound observations in subsequent pregnancies with Perlman Greenberg F, Stein F, Gresik V, Finegold MJ, Carpenter RJ, syndrome. Ultrasound Obstet Gynecol 1998;11:149-151. Riccardi VM, Beaudet AL. The Perlman familial nephroblastomatosis syndrome. American Journal of Medical Henneveld HT, van Lingen RA, Hamel BCJ, Stolte-Dijkstra I, Genetics 1986;24:101-110. van Hessen AJ. Perlman syndrome: four additional cases and review. Am J Med Genet 1999;86:439-446. Greenberg F, Copeland K, Gresik MV. Expanding the spectrum of Perlman syndrome. Am J Med Genet Schilke K, Schaefer F, Waldherr R, Rohrschneider W, John C, 1988;29:773-779. Himbert U, Mayatepek E, Tariverdian G. A case of Perlman Atlas Genet Cytogenet Oncol Haematol. 2007;11(2) 139 Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism) Piccione M, Corsello G syndrome: Fetal gigantism, renal dysplasia, and severe Pirgon O, Atabek ME, Akin F, Sert A. A case of Perlman neurological deficits. Am J Med Genet 2000;91:29-33. syndrome presenting with hemorrhagic hemangioma. J Pediatr Cohen MM jr, Neri G, Weksberg R. Overgrowth syndromes. Hematol Oncol 2006;28(8):531-533. Oxford University Press 2002;47-50. DeRoche M, Craffey A, Greenstein R, Borgida A. Antenatal This article should be referenced as such: Sonographic Features of Perlman Syndrome. J Ultrsound Med Piccione M, Corsello G. Perlman syndrome (renal 2004;23.561-564. hamartomas, nephroblastomatosis and fetal gigantism). Atlas Genet Cytogenet Oncol Haematol.2007;11(2):136-140. Piccione M, Cecconi M, Giuffrè M, Lo Curto M, Malacarne M, Piro E, Riccio A, Corsello G. Perlman syndrome: clinical report and nine-years follow-up. Am J Med Genet A 2005;139(2):131- 135. Atlas Genet Cytogenet Oncol Haematol. 2007;11(2) 140 .
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