Perlman syndrome (renal hamartomas, nephroblastomatosis and fetal gigantism)

The Perlman syndrome is characterized by polyhydramnios, fetal overgrowth, neonatal macrosomia, high neonatal mortality, macrocephaly, dysmorphic facial features, visceromegaly, nephroblastomatosis and a predisposition for Wilms tumor at very early age.

Inheritance is of an autosomal recessive nature.
 , Etiology: The genetic basis of the Perlman syndrome is unknown and there is no conclusive laboratory test to confirm the diagnosis. Although both sexes are affected, the sex ratio is 2M:1F. The diagnosis is based on characteristic features and confirmed by histological renal evidence. The syndrome has been described in both consanguineous and non-consanguineous couplings.

267000

C536399

2849 Perlman syndrome

-

Abnormalities :

Growth: oversize already evident in the prenatal and postnatal period.

Craniofacial: macrocephaly, prominent forehead, deep-set eyes, hypertelorism, epicantal folds, broad flat nasal bridge, everted upper lip, high arched palate, low-set ears (figure 1,2).

Visceral: nephromegaly, nephroblastomatosis, Wilms tumor (figure 3).Occasional abnormalities (table1):

Central nervous system abnormalities : agenesis of the corpus callosum; large cisterna magna; retrocerebellar and perichiasmatic leptomeningeal cysts, white matter hypoplasia and grey matter heterotopia involving the cerebellum and superior colliculi; choroid plexus hemangiomas; generalized cerebral atrophy with a marked deficit in the myelinization of the white matter; left periventricular ovoid cystic formation.

Cardiomegaly .

Congenital heart disease : interrupted aortic arch and anomalous coronary vessels and the dextroposition of the heart , muscular ventricular septal defect .

Intestinal malformations : intestinal malrotation and distal ileal atresia and volvulus and intestinal malrotation with caecum located on the midline, while most of the small intestine was located on the right ;

Hemangiomas : Capillary hemangioma in the left antecubital fossa, choroids plexus hemangioma and superficial cutaneus capillary hemangioma around the umbilicus.

Cryptorchidism.

Skeletal abnormalities : the absence of the normal widening of the lumbar interpediculate distances, rounded iliac wings, small sacrosciatic notches in a patient, and in patients showing crowded toes and bilateral calcaneovalgus deformity, genua recurvata, left metatarsus varus, right hallux varus, severe right convex dorsal and left convex lumbar scoliosis, lumbar hyperlordosis and crest iliac asymmetry, prominent xiphisternum .

Hypotonia .

Developmental delay.

Prenatal diagnosis is possible for families at risk for Perlman syndrome. The fetal overgrowth and particularly the OFC greater than the 90th centile for gestational age, that is associated with polyhydramnios, may be the first signs of Perlman syndrome. A prompt recognition and an accurate follow-up are recommended to offer these patients clinical assistance and to prevent the high morbidity and mortality in Perlman syndrome.

It is a clinical overlap with other overgrowth syndromes associated with Wilms tumor. Wilms tumor is also associated with Beckwith-Wiedemann syndrome, Sotos syndrome, Weaver syndrome and Simpson-Golabi-Behemel syndrome (table 2).

Pre and postnatal nephromegaly is evident. In a lot of the cases described neonatal nephromegaly is present at birth. In a patient, the neonatal nephromegaly is not evaluated and a patient described at birth had not organomegaly. Nephromegaly is associated with fetal lobulation. Nephroblastomatosis is characteristic. Histopathologic findings show cytodifferentiated nodular renal blastema and nests of immature glomeruli together with sclerotic glomeruli and primitive structures. Foci of hamartomatous tissue can be found in the medulla.
Nephroblastomatosis predisposes to the development of Wilms tumor, which is frequent and has been found in 7 of the 23 reported patients . Renal biopsy is necessary to evaluate the presence of Wilms tumor. Wilms tumor was diagnosed at the ages of 4 days, 8 months, 10 months, 10 months, 4 years and 6 months and 1 year and 8 months of age.
Organomegaly is frequent ( cardiomegaly, nephromegaly and hepato\/splenomegaly).
In the few patients who survived beyond neonatal age, a psychomotor delay of various degree was reported. A 12 year old girl is referred was moderately retarded, partly due to chemotherapy and radiation ; a 1 year-old patient had a development quotient (DQ) of 50, a nine-year-old patient had a normal cognitive level and the neurological examination was normal.

The prognosis is severe with neonatal death in most children ; only 5 cases have been described with a survival beyond the first year of life.

No chromosomal abnormalities have been found thus far, except for the case of Chernos et al , with a de novo extraG-positive band on the tip of the short arm of chromosome 11