Perlman syndrome

{{Short description|Overgrowth syndrome caused by DIS3L2 gene mutation}}

{{Infobox medical condition

| name = Perlman syndrome

| synonyms = Nephroblastomatosis-fetal ascites-macrosomia-Wilms tumor syndrome

| image =

| caption =

| pronounce =

| field = Medical genetics, pediatric oncology

| symptoms = Overgrowth, kidney dysplasia, facial dysmorphisms

| complications = Wilms' tumor

| onset = Prenatal or at birth

| duration = Lifelong

| types =

| causes = DIS3L2 mutation

| risks =

| diagnosis =

| differential = Beckwith–Wiedemann syndrome, Simpson–Golabi–Behmel syndrome

| prevention =

| treatment =

| medication =

| prognosis = High neonatal mortality

| frequency = 30 reported cases

| deaths =

| named after = Max Perlman

| QID = Q7169165

}}

Perlman syndrome (PS), also known as nephroblastomatosis-fetal ascites-macrosomia-Wilms tumor syndrome, is a rare overgrowth syndrome caused by autosomal recessive mutations in the DIS3L2 gene. PS is characterized by macrocephaly, neonatal macrosomia, nephromegaly, renal dysplasia, dysmorphic facial features, and increased risk for Wilms' tumor. The syndrome is associated with high neonatal mortality.

Signs and symptoms

Perlman syndrome may be detected as early as gestational week 18 by prenatal ultrasound. In the first trimester, cystic hygroma and thickened nuchal translucency may be observed. Macrosomia, macrocephaly, enlarged kidneys, macroglossia, cardiac abnormalities, and visceromegaly may become evident by the second and third trimesters. Polyhydramnios is frequently observed.

Characteristic facial features of Perlman syndrome include a hypotonic appearance with an open mouth, macrocephaly, upsweeping anterior scalp line, deep-set eyes, depressed nasal bridge, everted upper lip, and mild micrognathia.

Diagnosis is made based on the individual's phenotypic features and confirmed by histologic examination of the kidneys and/or molecular genetic testing. Bilateral kidney hamartomas with or without nephroblastomatosis are commonly observed.

Genetics

Perlman syndrome is caused by mutations in the DIS3L2 gene found on chromosome 2 at 2q37.2. DIS3L2 is involved in RNA degradation and cell cycle control. PS is genetically distinct from Beckwith–Wiedemann syndrome and Simpson–Golabi–Behmel syndrome, which are caused by mutations in 11p15.5 and GPC3 respectively. It is inherited in an autosomal recessive manner.

Management and prognosis

Perlman syndrome is associated with a high neonatal death rate due to renal failure and/or refractory hypoxemia. Most individuals who survive beyond the neonatal period develop a Wilms' tumor; nearly all display some degree of developmental delay. Treatment is supportive in nature.

Epidemiology

Perlman syndrome is a rare disease with an estimated incidence of less than 1 in 1,000,000. As of 2008, fewer than 30 patients had ever been reported in the world literature. PS has been described in both consanguineous and non-consanguineous couplings. The observed sex ratio is 2 males : 1 female.

References

{{Reflist |refs=

{{cite web | url = http://www.orpha.net//consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2849 | title = Perlman syndrome | access-date = 2010-10-21 | date = May 2008 | publisher = Orphanet}}

{{cite journal| author=Alessandri JL, Cuillier F, Ramful D, Ernould S, Robin S, de Napoli-Cocci S | display-authors=etal| title=Perlman syndrome: report, prenatal findings and review | journal=Am J Med Genet A | year= 2008 | volume= 146A | issue= 19 | pages= 2532–7 | pmid=18780370 | doi=10.1002/ajmg.a.32391| s2cid=205309637}}

{{cite journal |author=Perlman M |title=Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism, and multiple congenital anomalies. |journal=Am J Med Genet |volume=25 |issue=Pt 4 |pages=793–5 |date=December 1986 |pmid=3024486 |doi=10.1002/ajmg.1320250418}}

{{cite journal| author=Astuti D, Morris MR, Cooper WN, Staals RH, Wake NC, Fews GA | display-authors=etal| title=Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. | journal=Nat Genet | year= 2012 | volume= 44 | issue= 3 | pages= 277–84 | pmid=22306653 | doi=10.1038/ng.1071| s2cid=5363560| hdl=2066/93876 | hdl-access=free }}

{{cite web |last1=Piccione |first1=Maria |last2=Corsello |first2=Giovanni |title = Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism) |website=Atlas of Genetics and Cytogenetics in Oncology and Haematology |publisher=Institute for Biomedical Research of Salamanca |date = 2006-12-01 |url=https://atlasgeneticsoncology.org/cancer-prone-disease/10117/perlman-syndrome-(renal-hamartomas-nephroblastomatosis-and-fetal-gigantism) |access-date=2024-01-10}}

{{citation | last=Benacerraf | first=Beryl R. | year=2007 | title=Ultrasound of fetal syndromes | edition=2 | publisher=Elsevier Health Sciences | isbn=978-0-443-06641-2 | page=147 | url=https://books.google.com/books?id=1MHFF0UOKAUC}}

{{cite book |author=Rimoin DL, Emery AEH |title=Emery and Rimoin's Principles and Practice of Medical Genetics |volume=2 |edition=5 |publisher=Churchill Livingstone Elsevier |year=2007 | isbn=978-0-443-06870-6 |page=1522 | url=https://books.google.com/books?id=FfxPAQAAIAAJ }}

{{cite journal| author=Liban E, Kozenitzky IL| title=Metanephric hamartomas and nephroblastomatosis in siblings. | journal=Cancer | year= 1970 | volume= 25 | issue= 4 | pages= 885–8 | pmid=4315293 | doi=10.1002/1097-0142(197504)35:4<1212::AID-CNCR2820350427>3.0.CO;2-2}}

{{cite journal| author=Piccione M, Cecconi M, Giuffrè M, Lo Curto M, Malacarne M, Piro E | display-authors=etal| title=Perlman syndrome: clinical report and nine-year follow-up. | journal=Am J Med Genet A | year= 2005 | volume= 139A | issue= 2 | pages= 131–5 | pmid=16278893 | doi=10.1002/ajmg.a.30994| s2cid=26889314}}

{{cite journal| author=Neri G, Martini-Neri ME, Katz BE, Opitz JM| title=The Perlman syndrome: familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies. | journal=Am J Med Genet | year= 1984 | volume= 19 | issue= 1 | pages= 195–207 | pmid=6093533 | doi=10.1002/ajmg.1320190120}}

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