Perlman syndrome (PS), also known as nephroblastomatosis-fetal ascites-macrosomia-Wilms tumor syndrome, is a rare

overgrowth syndrome Overgrowth syndromes in children constitute a group of rare disorders that are characterised by tissue hypertrophy. Individual overgrowth syndromes have been shown to overlap with regard to clinical and radiologic features. The details of the gene ...

caused by

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

mutations in the '' DIS3L2'' gene. PS is characterized by

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 Heredity, familial genetic characteristic. People diagnosed with macrocephaly will receive further medical ...

, neonatal

macrosomia Large for gestational age (LGA) is a term used to describe infants that are born with an abnormally high weight, specifically in the 90th percentile or above, compared to other babies of the same developmental age. Macrosomia is a similar term tha ...

nephromegaly Nephromegaly is the process whereby a kidney or both kidneys become enlarged. Both Autosomal dominant polycystic kidney disease, autosomal dominant and autosomal recessive polycystic kidney disease can cause nephromegaly. References Further ...

, renal dysplasia,

dysmorphic A dysmorphic feature is an abnormal difference in body structure. It can be an isolated finding in an otherwise normal individual, or it can be related to a congenital disorder, genetic syndrome or birth defect. Dysmorphology is the study of dysm ...

facial features, and 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 ...

. The syndrome is associated with high

neonatal mortality Perinatal mortality (PNM) is the death of a fetus or neonate and is the basis to calculate the perinatal mortality rate. ''Perinatal'' means "relating to the period starting a few weeks before birth and including the birth and a few weeks after bi ...

Signs and symptoms

Perlman syndrome may be detected as early as gestational week 18 by

prenatal ultrasound Obstetric ultrasonography, or prenatal ultrasound, is the use of medical ultrasonography in pregnancy, in which sound waves are used to create real-time visual images of the developing embryo or fetus in the uterus (womb). The procedure is a stand ...

. In the first trimester,

cystic hygroma A cystic hygroma is a form of lymphatic malformation. It 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 s ...

and thickened nuchal translucency may be observed.

Macrosomia Large for gestational age (LGA) is a term used to describe infants that are born with an abnormally high weight, specifically in the 90th percentile or above, compared to other babies of the same developmental age. Macrosomia is a similar term tha ...

, enlarged kidneys,

macroglossia Macroglossia is the medical term for an unusually large tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties in speaking, eating, Dysphagia, swallowing and sleeping. Macroglossia is uncommon, and usually occurs ...

, cardiac abnormalities, and visceromegaly may become evident by the second and third trimesters.

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 ...

is frequently observed. Characteristic facial features of Perlman syndrome include a

hypotonic In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective memb ...

appearance with an open mouth,

, upsweeping anterior scalp line, deep-set eyes, depressed

nasal bridge The nasal bridge is the upper part of the nose, where the nasal bones and surrounding soft tissues provide structural support. While commonly discussed in human anatomy, nasal bridges exist in various forms across many vertebrates, particularl ...

, everted upper lip, and mild

micrognathia Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnorma ...

. Diagnosis is made based on the individual's phenotypic features and confirmed by histologic examination of the kidneys and/or molecular

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

. 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 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 ei ...

at 2q37.2. ''DIS3L2'' is involved in RNA degradation and cell cycle control. PS is genetically distinct from

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 * Hemihypertroph ...

and

Simpson–Golabi–Behmel syndrome Simpson–Golabi–Behmel syndrome (SGBS) is a rare inherited congenital disorder that can cause craniofacial, skeletal, vascular, cardiac, and renal abnormalities. There is a high prevalence of cancer associated in those with SGBS which includes ...

, which are caused by mutations in 11p15.5 and ''

GPC3 Glypican-3 is a protein that, in humans, is encoded by the ''GPC3'' gene. The ''GPC3'' gene is located on human X chromosome (Xq26) where the most common gene (Isoform 2, GenBank Accession No.: NP_004475) encodes a 70-kDa core protein with 580 am ...

'' 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 Hypoxemia (also spelled hypoxaemia) is an abnormally low level of oxygen in the blood. More specifically, it is oxygen deficiency in arterial blood. Hypoxemia is usually caused by pulmonary disease. Sometimes the concentration of oxygen in the ...

. Most individuals who survive beyond the neonatal period develop a

; nearly all display some degree of

developmental delay The term developmental delay can refer to: *Global developmental delay, an umbrella term used when children are significantly delayed in two or more areas of development *Specific developmental disorder, a classification of disorders characterize ...

. Treatment is supportive in nature.

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, the term orphan disease describes a rare disease whose rarity results in little or no funding or research for treatments, without financi ...

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 Consanguinity (from Latin '' consanguinitas'' 'blood relationship') is the characteristic of having a kinship with a relative who is descended from a common ancestor. Many jurisdictions have laws prohibiting people who are closely related by blo ...

and non-consanguineous couplings. The observed sex ratio is 2 males : 1 female.

References

External links