Perlman syndrome

Title

Other Names:

Nephroblastomatosis fetal ascites macrosomia and wilms tumor; Renal hamartomas, nephroblastomatosis, and fetal gigantism

Categories:

Congenital and Genetic Diseases; Hereditary Cancer Syndromes; Kidney and Urinary Diseases; Congenital and Genetic Diseases; Hereditary Cancer Syndromes; Kidney and Urinary Diseases; Rare Cancers See More

Summary Summary

Perlman syndrome causes overgrowth in infancy and affects many different parts of the body. Babies with Perlman syndrome are bigger than most babies and have large heads, kidneys, and livers. In addition, they may have low muscle tone, distinctive facial features, and developmental delay. Over time, people with Perlman syndrome have an increased chance to develop Wilms tumor, a rare kidney cancer that primarily affects children. Perlman syndrome is caused by genetic changes (variants) in the DIS3L2 gene. It is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, a clinical exam, and may be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms.^[1]^[2]^[3]^[4]

Last updated: 3/2/2021

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Deeply set eye	Deep set eye Deep-set eyes Sunken eye [ more ]	0000490
Global developmental delay		0001263
Hepatomegaly	Enlarged liver	0002240
High forehead		0000348
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Muscular hypotonia	Low or weak muscle tone	0001252
Open mouth	Gaped jawed appearance Gaped mouthed appearance Slack jawed appearance [ more ]	0000194
Retrognathia	Receding chin Receding lower jaw Weak chin Weak jaw [ more ]	0000278
Round face	Circular face Round facial appearance Round facial shape [ more ]	0000311
Short nose	Decreased length of nose Shortened nose [ more ]	0003196
Smooth philtrum		0000319
Specific learning disability		0001328
Tall stature	Increased body height	0000098
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431
30%-79% of people have these symptoms
Abnormal pancreas morphology	Abnormally shaped pancreas	0012090
Anteverted nares	Nasal tip, upturned Upturned nasal tip Upturned nose Upturned nostrils [ more ]	0000463
Broad alveolar ridges		0000187
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
High, narrow palate	Narrow, high-arched roof of mouth Narrow, highly arched roof of mouth [ more ]	0002705
Hyperinsulinemia		0000842
Hypoplasia of penis	Underdeveloped penis	0008736
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Nephroblastoma		0002667
Posteriorly rotated ears	Ears rotated toward back of head	0000358
Thickened helices		0000391
5%-29% of people have these symptoms
Bilateral single transverse palmar creases		0007598
Capillary hemangioma	Strawberry birthmark	0005306
Dolichocephaly	Long, narrow head Tall and narrow skull [ more ]	0000268
Femoral hernia		0100541
Inguinal hernia		0000023
Naevus flammeus of the eyelid	Port-wine stain on eyelid	0010733
Ptosis	Drooping upper eyelid	0000508
Status epilepticus	Repeated seizures without recovery between them	0002133
Percent of people who have these symptoms is not available through HPO
Abnormal facial shape	Unusual facial appearance	0001999
Abnormality of the cardiovascular system	Cardiovascular abnormality	0001626
Agenesis of corpus callosum		0001274
Ascites	Accumulation of fluid in the abdomen	0001541
Autosomal recessive inheritance		0000007
Congenital diaphragmatic hernia		0000776
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Distal ileal atresia		0200116
Edema	Fluid retention Water retention [ more ]	0000969
Growth abnormality	Abnormal growth Growth issue [ more ]	0001507
Hypoplasia of the abdominal wall musculature		0005247
Interrupted aortic arch		0011611
Large for gestational age	Birth weight > 90th percentile Birthweight > 90th percentile [ more ]	0001520
Long upper lip	Elongation of upper lip Increased height of upper lip Increased vertical length of upper lip [ more ]	0011341
Nephroblastomatosis		0008643
Nephrogenic rest		0100880
Pancreatic islet-cell hyperplasia		0004510
Polyhydramnios	High levels of amniotic fluid	0001561
Renal hamartoma		0008696
Tented upper lip vermilion		0010804
Visceromegaly		0003271
Volvulus		0002580

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Perlman syndrome occurs when the DIS3L2 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[2]^[4]

Last updated: 3/4/2021

Inheritance Inheritance

Perlman syndrome is inherited in an autosomal recessive pattern. All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must have a pathogenic variant to have the condition.

People with autosomal recessive conditions inherit one variant from each of their parents. The parents, who each have one gene variant, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms. When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.^[2]

Last updated: 3/4/2021

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The principle differential diagnoses are the Beckwith-Wiedemann (BWS) and Simpson-Golabi-Behmel syndromes (see these terms): mutations the GPC3 gene were excluded as being causative anomalies in several publications and genetic or epigenetic alterations of the 11p15 region (involved in BWS) have never been reported in patients with Perlman syndrome, despite the strong phenotypic similarities between the two syndromes. Visit the Orphanet disease page for more information.

Conditions with similar signs and symptoms from Orphanet

The principle differential diagnoses are the Beckwith-Wiedemann (BWS) and Simpson-Golabi-Behmel syndromes (see these terms): mutations the GPC3 gene were excluded as being causative anomalies in several publications and genetic or epigenetic alterations of the 11p15 region (involved in BWS) have never been reported in patients with Perlman syndrome, despite the strong phenotypic similarities between the two syndromes.

Visit the Orphanet disease page for more information.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Perlman syndrome. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Perlman syndrome. OMIM. September 2016; http://www.omim.org/entry/267000.
Morris MR, Astuti D, Maher ER. Perlman syndrome: overgrowth, Wilms tumor predisposition and DIS3L2. Am J Med Genet C Semin Med Genet. May 2013; 63C(2):106-13. https://pubmed.ncbi.nlm.nih.gov/23613427/.
Soma N, Higasimoto K, Imamura M, Saitoh A, Soejima H, Nagasaki K. Long term survival of a patient with Perlman syndrome due to novel compound heterozygous missense mutations in RNB domain of DIS3L2. Am J Med Genet A. Apr 2017; 173(4):1077-1081. https://pubmed.ncbi.nlm.nih.gov/28328139/.
Astuti D, Morris M, Cooper WN, Staals RH, Wake NC, Fews GA, et al. Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nat Genet. Feb 5, 2012; 44(3):277-84. https://pubmed.ncbi.nlm.nih.gov/22306653/.