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Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism)

Identity

Note The Perlman syndrome is characterized by polyhydramnios, fetal overgrowth, neonatal macrosomia, high neonatal mortality, macrocephaly, dysmorphic facial features, visceromegaly, nephroblastomatosis and a predisposition for Wilms tumor at very early age.
Inheritance Inheritance is of an autosomal recessive nature.
Etiology: The genetic basis of the Perlman syndrome is unknown and there is no conclusive laboratory test to confirm the diagnosis. Although both sexes are affected, the sex ratio is 2M:1F. The diagnosis is based on characteristic features and confirmed by histological renal evidence. The syndrome has been described in both consanguineous and non-consanguineous couplings.
 
  Figure 1,2 : Macrocephaly, hypertelorism, epicanthus, broad flat nasal bridge, anteverted upper lip, axial hypotonia. Figure 3 : Abdominal ultrasound scan at 6 months of age: nephromegaly with lobulated contoured kidneys and loss of corticomedullary differentiation.

Clinics

Phenotype and clinics Abnormalities :
  • Growth: oversize already evident in the prenatal and postnatal period.
  • Craniofacial: macrocephaly, prominent forehead, deep-set eyes, hypertelorism, epicantal folds, broad flat nasal bridge, everted upper lip, high arched palate, low-set ears (figure 1,2).
  • Visceral: nephromegaly, nephroblastomatosis, Wilms tumor (figure 3). Occasional abnormalities (table1):
  • Central nervous system abnormalities : agenesis of the corpus callosum; large cisterna magna; retrocerebellar and perichiasmatic leptomeningeal cysts, white matter hypoplasia and grey matter heterotopia involving the cerebellum and superior colliculi; choroid plexus hemangiomas; generalized cerebral atrophy with a marked deficit in the myelinization of the white matter; left periventricular ovoid cystic formation.
  • Cardiomegaly .
  • Congenital heart disease : interrupted aortic arch and anomalous coronary vessels and the dextroposition of the heart , muscular ventricular septal defect .
  • Intestinal malformations : intestinal malrotation and distal ileal atresia and volvulus and intestinal malrotation with caecum located on the midline, while most of the small intestine was located on the right ;
  • Hemangiomas : Capillary hemangioma in the left antecubital fossa, choroids plexus hemangioma and superficial cutaneus capillary hemangioma around the umbilicus.
  • Cryptorchidism.
  • Skeletal abnormalities : the absence of the normal widening of the lumbar interpediculate distances, rounded iliac wings, small sacrosciatic notches in a patient, and in patients showing crowded toes and bilateral calcaneovalgus deformity, genua recurvata, left metatarsus varus, right hallux varus, severe right convex dorsal and left convex lumbar scoliosis, lumbar hyperlordosis and crest iliac asymmetry, prominent xiphisternum .
  • Hypotonia .
  • Developmental delay.

    Prenatal diagnosis is possible for families at risk for Perlman syndrome. The fetal overgrowth and particularly the OFC greater than the 90th centile for gestational age, that is associated with polyhydramnios, may be the first signs of Perlman syndrome. A prompt recognition and an accurate follow-up are recommended to offer these patients clinical assistance and to prevent the high morbidity and mortality in Perlman syndrome.

  •  
      Table1 : Characteristic clinical features of Perlman syndrome Table 2: Comparison of Perlman, Beckwith-Wiedemann, Sotos, Weaver and Simpson-Golabi-Behmel syndromes.
    Differential diagnosis It is a clinical overlap with other overgrowth syndromes associated with Wilms tumor. Wilms tumor is also associated with Beckwith-Wiedemann syndrome, Sotos syndrome, Weaver syndrome and Simpson-Golabi-Behemel syndrome (table 2).
     
    Evolution Pre and postnatal nephromegaly is evident. In a lot of the cases described neonatal nephromegaly is present at birth. In a patient, the neonatal nephromegaly is not evaluated and a patient described at birth had not organomegaly. Nephromegaly is associated with fetal lobulation. Nephroblastomatosis is characteristic. Histopathologic findings show cytodifferentiated nodular renal blastema and nests of immature glomeruli together with sclerotic glomeruli and primitive structures. Foci of hamartomatous tissue can be found in the medulla.
    Nephroblastomatosis predisposes to the development of Wilms tumor, which is frequent and has been found in 7 of the 23 reported patients . Renal biopsy is necessary to evaluate the presence of Wilms tumor. Wilms tumor was diagnosed at the ages of 4 days, 8 months, 10 months, 10 months, 4 years and 6 months and 1 year and 8 months of age.
    Organomegaly is frequent ( cardiomegaly, nephromegaly and hepato/splenomegaly).
    In the few patients who survived beyond neonatal age, a psychomotor delay of various degree was reported. A 12 year old girl is referred was moderately retarded, partly due to chemotherapy and radiation ; a 1 year-old patient had a development quotient (DQ) of 50, a nine-year-old patient had a normal cognitive level and the neurological examination was normal.
    Prognosis The prognosis is severe with neonatal death in most children ; only 5 cases have been described with a survival beyond the first year of life.

    Cytogenetics

    Note No chromosomal abnormalities have been found thus far, except for the case of Chernos et al , with a ³de novo² extraG-positive band on the tip of the short arm of chromosome 11

    External links

    OrphanetPerlman syndrome

    Bibliography

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    Renal hamartomas and nephroblastomatosis with fetal gigantism: a familial syndrome.
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    Syndrome of fetal gigantism, renal hamartomas, and nephroblastomatosis with Wilms' tumor.
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    The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies.
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    Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism, and multiple congenital anomalies.
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    The Perlman familial nephroblastomatosis syndrome.
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    Expanding the spectrum of the Perlman syndrome.
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    Perlman syndrome: report of a case and results of molecular studies.
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    A case of Perlman syndrome associated with a cytogenetic abnormality of chromosome 11.
    Chernos JE, Fowlow SB, Cox DM
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    Perlman and Wiedemann-Beckwith syndromes: two distinct conditions associated with Wilms' tumour.
    Grundy RG, Pritchard J, Baraitser M, Risdon A, Robards M
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    Perlman syndrome: report of a case with additional radiographic findings.
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    Extending the overlap of three congenital overgrowth syndromes.
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    Perlman syndrome--a cause of enlarged, hyperechogenic kidneys.
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    Perlman syndrome: a case report emphasizing its similarity to and distinction from Beckwith-Wiedemann and prune-belly syndromes.
    Fahmy J, Kaminsky CK, Parisi MT
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    Prenatal ultrasound observations in subsequent pregnancies with Perlman syndrome.
    van der Stege JG, van Eyck J, Arabin B
    Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. 1998 ; 11 (2) : 149-151.
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    Perlman syndrome: four additional cases and review.
    Henneveld HT, van Lingen RA, Hamel BC, Stolte-Dijkstra I, van Essen AJ
    American journal of medical genetics. 1999 ; 86 (5) : 439-446.
    PMID 10508986
     
    A case of Perlman syndrome: fetal gigantism, renal dysplasia, and severe neurological deficits.
    Schilke K, Schaefer F, Waldherr R, Rohrschneider W, John C, Himbert U, Mayatepek E, Tariverdian G
    American journal of medical genetics. 2000 ; 91 (1) : 29-33.
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    Overgrowth syndromes.
    Cohen MM jr, Neri G, Weksberg R
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    Antenatal sonographic features of Perlman syndrome.
    DeRoche ME, Craffey A, Greenstein R, Borgida AF
    Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. 2004 ; 23 (4) : 561-564.
    PMID 15098877
     
    Perlman syndrome: clinical report and nine-year follow-up.
    Piccione M, Cecconi M, Giuffrˆ® M, Lo Curto M, Malacarne M, Piro E, Riccio A, Corsello G
    American journal of medical genetics. Part A. 2005 ; 139 (2) : 131-135.
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    A case of Perlman syndrome presenting with hemorrhagic hemangioma.
    Pirgon O, Atabek ME, Akin F, Sert A
    Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology. 2006 ; 28 (8) : 531-533.
    PMID 16912594
     
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    Contributor(s)

    Written12-2006Maria Piccione, Giovanni Corsello

    Citation

    This paper should be referenced as such :
    Piccione, M ; Corsello, G
    Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism)
    Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):136-140.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Kprones/PerlmanID10117.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Tue Aug 26 15:56:24 CEST 2014


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