Perlman syndrome (PS) (also called renal hamartomas, nephroblastomatosis and fetal gigantism) is a rare overgrowth disorder present at birth. It is characterized by

polyhydramnios Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in about 1% of pregnancies. It is typically diagnosed when the amniotic fluid index (AFI) is greater than 24 cm. There are two clini ...

and fetal overgrowth, including

macrocephaly Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to ...

, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for

Wilms' tumor Wilms' tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children, rarely in adults.; and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German sur ...

at an early age. The prognosis for Perlman syndrome is poor and it is associated with a high neonatal mortality. Perlman syndrome is an uncommon

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorde ...

grouped with overgrowth syndrome in which an abnormal increase is often noted at birth in the size of the body or a body part of the infant. The disorder, also called renal hamartomas, nephroblastomatosis and fetal gigantism, has also been grouped with

Renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, res ...

. The characteristic features include

, fetal overgrowth, including

, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for

at an early age.

Signs and symptoms

Genetics

The gene thought to cause some of the cases of Perlman syndrome is '' DIS3L2'' found on

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost ...

at 2q37.2 and is thought to have an important role in the mitotic cell cycle. Although both sexes are affected, the sex ratio of male to female is 2:1. The syndrome has been described in both

consanguineous Consanguinity ("blood relation", from Latin '' consanguinitas'') is the characteristic of having a kinship with another person (being descended from a common ancestor). Many jurisdictions have laws prohibiting people who are related by blood fro ...

and non-consanguineous couplings. No chromosomal abnormalities have been observed, except for in the case of Chernos et al., which showed a ''de novo'' mutation — an extra G positive band, a

genetic mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

that neither parent possessed nor transmitted — on the tip of the short arm of

chromosome 11 Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the to ...

Diagnosis

The

diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...

of Perlman syndrome is based on observed phenotypic features and confirmed by

histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...

examination of the kidneys.

Prenatal diagnosis Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health ...

is possible for families that have a genetic disposition for Perlman syndrome although there is no conclusive laboratory test to confirm the diagnosis. Fetal overgrowth, particularly with an

occipitofrontal circumference Occipitofrontal is a term relating to the occiput and the frontal direction, as in: * Occipitofrontal fasciculus, association fibers in the brain *Occipito-anterior A cephalic presentation or head presentation or head-first presentation is a sit ...

(OFC) greater than the 90th centile for

gestational age In obstetrics, gestational age is a measure of the age of a pregnancy which is taken from the beginning of the woman's last menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method if available. Su ...

, as well as an excess of

amniotic fluid The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwe ...

in the

amniotic sac The amniotic sac, also called the bag of waters or the membranes, is the sac in which the embryo and later fetus develops in amniotes. It is a thin but tough transparent pair of membranes that hold a developing embryo (and later fetus) until sh ...

(polyhydramnios), may be the first signs of Perlman. Using ultrasound diagnosis, Perlman syndrome has been detected at 18 weeks. During the

first trimester Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

, the common abnormalities of the syndrome observed by ultrasound include

cystic hygroma A cystic hygroma is an abnormal growth that usually appears on a baby's neck or head. It consists of one or more cysts and tends to grow larger over time. The disorder usually develops while the fetus is still in the uterus, but can also appear a ...

and a thickened nuchal lucency. Common findings for the second and third trimesters include macrosomia, enlarged kidneys, renal tumors (both hamartoma and Wilms), cardiac abnormalities and visceromegaly. Prompt recognition and identification of the disorder along with accurate follow-up and clinical assistance is recommended as the prognosis for Perlman is severe and associated with a high neonatal death rate.

Differential diagnosis

Perlman syndrome shares clinical overlaps with other overgrowth disorders, with similarities to

Beckwith–Wiedemann syndrome Beckwith–Wiedemann syndrome (; abbreviated BWS) is an overgrowth disorder usually present at birth, characterized by an increased risk of childhood cancer and certain congenital features. A minority (97th centile) * Macroglossia * Hemihyperpla ...

and

Simpson–Golabi–Behmel syndrome Simpson–Golabi–Behmel syndrome (SGBS), is a rare inherited congenital disorder that can cause craniofacial, skeletal, cardiac, and renal abnormalities. The syndrome is inherited in an X-linked recessive fashion, where males express the phenoty ...

having been particularly emphasized in scientific study. Similarities with Beckwith-Wiedemann syndrome include polyhydramnios, macrosomia, nephromegaly and hypoglycaemia. It is the distinctive facial

dysmorphology Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related t ...

of Perlman, including deep-set eyes, depressed

nasal bridge The nasal bridge is the upper, bony part of the human nose, which overlies the nasal bones. Association with epicanthic folds Low-rooted nasal bridges are closely associated with epicanthic folds. A lower nasal bridge is more likely to cause a ...

, everted upper lip, and macrocephaly which allows the two conditions to be distinguished from one another. Diagnosis of Perlman syndrome also overlaps with other disorders associated with Wilms tumor, namely,

Sotos syndrome Sotos syndrome is a rare genetic disorder characterized by excessive physical growth during the first years of life. Excessive growth often starts in infancy and continues into the early teen years. The disorder may be accompanied by autism, mild ...

and

Weaver syndrome Weaver syndrome is a rare autosomal dominant genetic disorder associated with rapid growth beginning in the prenatal period and continuing through the toddler and youth years. It is characterized by advanced osseous maturation and distinctive cra ...

Treatment

Epidemiology

Perlman syndrome is a

rare disease A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discov ...

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.

References

External links

{{Phakomatoses and other congenital malformations not elsewhere classified Genetic disorders with OMIM but no gene Rare syndromes Syndromes affecting head size Syndromes with craniofacial abnormalities Syndromes with tumors