Perlman syndrome
Encyclopedia
Perlman syndrome (also called renal hamartomas, nephroblastomatosis and fetal gigantism) is a rare overgrowth disorder
present at birth. It is characterized by polyhydramnios
and fetal overgrowth, including macrocephaly
, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms' tumor
at an early age. The prognosis for Perlman syndrome is severe and associated with a high neonatal mortality.
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
. The characteristic features include polyhydramnios
, fetal overgrowth, including macrocephaly
, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms' tumor
at an early age.
with an estimated incidence of less than 1 in 1,000,000. As of 2008, less than 30 patients had ever been reported in the world literature.
The genetic basis of the syndrome is unknown though an autosomal recessive mode of inheritance
is suggested. Although both sexes are affected, the sex ratio of male to female is 2:1. The syndrome has been described in both consanguineous 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 that neither parent possessed nor transmitted— on the tip of the short arm of chromosome 11
.
of Perlman syndrome is based on observed phenotypic features and confirmed by histological examination of the kidneys. Prenatal diagnosis
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 orbitofrontal cortex
(OFC) greater than the 90th centile for gestational age
, as well as an excess of amniotic fluid
in the amniotic sac
(polyhydramnios), may be the first signs of Perlman. Using ultrasound diagnosis, Perlman syndrome has been detected at 18 weeks. During the first trimester, the common abnormalities of the syndrome observed by ultrasound include cystic hygroma
and a thickened nuchal lucency. Common findings for the second and third trimesters include macrosomia, enlarged kidneys, renal tumors (both hamartona and Wilm’s), 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.
having been particularly emphasized in scientific study. Similarities with Beckwith-Wiedemann syndrome, include polyhydramnios, macrosomia, nephromegaly and hypoglycaemia. It is the distinctive facial dysmorphology of Perlman, including deep-set eyes, depressed nasal bridge
, everted upper lip, and macrocephaly which allows the two conditions to be distinguished from one another. Diagnosis of Perlman syndrome also overlap with other disorders associated with Wilms tumor namely Sotos syndrome
and Weaver syndrome
.
Overgrowth syndrome
Overgrowth syndrome is a group of genetic disorders in which there is an abnormal increase in the size of the body or a body part that is often noted at birth. Examples of overgrowth syndromes include neurofibromatosis, Sotos syndrome, Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome,...
present at birth. It is characterized by polyhydramnios
Polyhydramnios
Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in 0.2 to 1.6% of pregnancies,,...
and fetal overgrowth, including macrocephaly
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms' tumor
Wilms' tumor
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon who first described this kind of tumor....
at an early age. The prognosis for Perlman syndrome is severe and associated with a high neonatal mortality.
Signs and symptoms
Perlman syndrome is an uncommon genetic disorderGenetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
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
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...
. The characteristic features include polyhydramnios
Polyhydramnios
Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in 0.2 to 1.6% of pregnancies,,...
, fetal overgrowth, including macrocephaly
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms' tumor
Wilms' tumor
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon who first described this kind of tumor....
at an early age.
Epidemiology
Perlman syndrome is a rare diseaseRare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
with an estimated incidence of less than 1 in 1,000,000. As of 2008, less than 30 patients had ever been reported in the world literature.
Genetics
Inheritance
Inheritance is the practice of passing on property, titles, debts, rights and obligations upon the death of an individual. It has long played an important role in human societies...
is suggested. Although both sexes are affected, the sex ratio of male to female is 2:1. The syndrome has been described in both consanguineous 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 that neither parent possessed nor transmitted— on the tip of the short arm of chromosome 11
Chromosome 11 (human)
thumb|right|Chromosome 11 ChartChromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 134.5 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells...
.
Diagnosis
The diagnosisDiagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
of Perlman syndrome is based on observed phenotypic features and confirmed by histological examination of the kidneys. Prenatal diagnosis
Prenatal diagnosis
Prenatal diagnosis or prenatal screening is testing for diseases or conditions in a fetus or embryo before it is born. The aim is to detect birth defects such as neural tube defects, Down syndrome, chromosome abnormalities, genetic diseases and other conditions, such as spina bifida, cleft palate,...
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 orbitofrontal cortex
Orbitofrontal cortex
The orbitofrontal cortex is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making...
(OFC) greater than the 90th centile for gestational age
Gestational age
Gestational age relates to the age of an embryo or fetus . There is some ambiguity in how it is defined:*In embryology, gestational age is the time elapsed since conception. This interval is also termed fertilisation age....
, as well as an excess of amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of amniotic fluid :...
in the amniotic sac
Amniotic sac
The amniotic sac is the sac in which the fetus develops in amniotes. It is a tough but thin transparent pair of membranes, which hold a developing embryo until shortly before birth. The inner membrane, the amnion, contains the amniotic fluid and the fetus. The outer membrane, the Chorion,...
(polyhydramnios), may be the first signs of Perlman. Using ultrasound diagnosis, Perlman syndrome has been detected at 18 weeks. During the first trimester, the common abnormalities of the syndrome observed by ultrasound include cystic hygroma
Cystic hygroma
A cystic hygroma is a congenital multiloculated lymphatic lesion that can arise anywhere, but is classically found in the left posterior triangle of the neck. This is the most common form of lymphangioma. It contains large cyst like cavities containing watery fluid.Microscopically cystic hygroma...
and a thickened nuchal lucency. Common findings for the second and third trimesters include macrosomia, enlarged kidneys, renal tumors (both hamartona and Wilm’s), 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 and Simpson-Golabi-Behmel syndromeSimpson-Golabi-Behmel syndrome
Simpson–Golabi–Behmel syndrome , also called Bulldog syndrome, Sara Agers syndrome, Golabi–Rosen syndrome, Simpson dysmorphia syndrome or X-linked dysplasia gigantism syndrome , is a rare inherited congenital disorder with widely variable expression, causing craniofacial and other abnormalities.It...
having been particularly emphasized in scientific study. Similarities with Beckwith-Wiedemann syndrome, include polyhydramnios, macrosomia, nephromegaly and hypoglycaemia. It is the distinctive facial dysmorphology of Perlman, including deep-set eyes, depressed nasal bridge
Nasal bridge
The nasal bridge is the name given to the upper, bony part of the nose, overlying the nasal bones.A lower or higher than average nasal bridge can be a sign of various genetic disorders, such as fetal alcohol syndrome. A flat nasal bridge can be a sign of Down syndrome, Fragile X syndrome, and Fetal...
, everted upper lip, and macrocephaly which allows the two conditions to be distinguished from one another. Diagnosis of Perlman syndrome also overlap with other disorders associated with Wilms tumor namely Sotos syndrome
Sotos syndrome
Sotos syndrome is a rare genetic disorder characterized by excessive physical growth during the first 2 to 3 years of life. The disorder may be accompanied by autism mild mental retardation, delayed motor, cognitive, and social development, hypotonia , and speech impairments...
and Weaver syndrome
Weaver syndrome
Weaver syndrome is a congenital disorder associated with rapid growth beginning in the prenatal period, a characteristic facial appearance and certain skeletal features. It was first described by Weaver in 1974....
.