Greenberg Dysplasia

Greenberg dysplasia is a very rare lethal skeletal dysplasia characterized by fetal hydrops, short limbs and abnormal chondro-osseous calcification. The disease is characterized by early in utero lethality and affected fetuses are considered as nonviable.

Epidemiology

Less than ten cases have been published so far.

Clinical description

The main features include fetal hydrops, severe short-limbed dwarfism and a marked disorganization of chondro-osseous calcification. Unusual facial features, cystic hygroma, incomplete lung lobation, pulmonary hypoplasia, extramedullary hematopoiesis, intestinal malrotation and polydactyly may occur.

Etiology

The causative gene has been recently identified as that encoding the lamin B receptor (LBR gene), a member of the sterol reductase family. Mutations in LBR have also been reported to cause Pelger-Huët anomaly (PHA), but in this case transmission occurs in an autosomal dominant manner. PHA is characterized by hypolobulated granulocyte nuclei and abnormal chromatin structure in granulocytes. It has been suggested that homozygous LBR mutations result in distinct mild (PHA homozygosity) or severe (Greenberg skeletal dysplasia) phenotypes based on allelic heterogeneity.

Diagnostic methods

Radiologic abnormalities include a distinctive 'moth-eaten'' appearance of the long bones, marked platyspondyly with multiple abnormal ossification centers, ectopic ossification of the ribs, sternum, pelvis and epiphysis, and deficient ossification of the skull. Histological characterization shows marked disorganization of the cartilaginous architecture, with absence of cartilage column formation, nodular calcifications in cartilage and islands of cartilage surrounded by bone. Greenberg dysplasia has been shown to be associated with an abnormality of cholesterol biosynthesis.

Differential diagnosis

Greenberg dysplasia should be considered in differential diagnosis of cases with severe fetal hydrops (see this term) and phokomelia on antenatal sonography.

Antenatal diagnosis

Prenatal ultrasound diagnosis at 20 weeks of gestation will usually reveal the polyhydramnios, hydrops fetalis, severely short limbs, and cystic hygroma. Sterol profile analysis may be a useful diagnostic tool and can be used for prenatal diagnosis, as can molecular analysis if the mutation in the family is known.

Genetic counseling

It is inherited as an autosomal recessive trait.