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Genetic and Rare Diseases Information Center (GARD)

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Hydrops, Ectopic calcification, Moth-eaten skeletal dysplasia

Other Names for this Disease
  • Autosomal recessive lethal chondrodystrophy with congenital hydrops
  • Greenberg dysplasia
  • Greenberg skeletal dysplasia
  • HEM
  • HEM dysplasia
More Names
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Your Question

Since my daughter passed from HEM, I have checked the leading publications for news of Greenburg's dysplasia. I am both happy and perplexed at the lack of mention. Are there truly only a handful of cases? Has this horrible condition not captured the eye of the research community? I was told that my daughter's death (after three weeks in the NICU) was due to this extraordinary mutation, and that her survival (although short) was beyond expectation. I am desperately looking for more information. Both my husband and I are carriers for the mutation and have many siblings. Our siblings have concerns over the prevalence of this mutation. I am not a medical professional. I would appreciate any response in "layman's terms" please.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is HEM?

HEM (hydrops fetalis, ectopic calcifications, "moth-eaten" skeletal dysplasia) is a very rare type of lethal skeletal dysplasia. According to the reported cases of HEM in the medical literature, the condition's main features are hydrops fetalis, dwarfism with severely shortened limbs and relatively normal-sized hands and feet, a "moth-eaten" appearance of the skeleton, flat vertebral bodies and ectopic calcifications. HEM is an autosomal recessive condition caused by a mutation in the lamin B receptor (LBR) gene.[1] No treatment or cure is currently known for HEM.
Last updated: 7/17/2009

What are the signs and symptoms of HEM?

The diagnostic findings of HEM (hydrops fetalis, severe micromelia, and ectopic calcification) have been present in all cases reported in the medical literature thus far. The following are several of the other signs and symptoms that have been reported in some patients with HEM [2]:

  • Polydactyly (presence of more than 5 fingers on the hands or 5 toes on the feet)
  • Reduced number of ribs
  • Omphalocele
  • Intestinal malformation
  • Abnormal fingernails
  • Less than normal number of lobes in the lung (hypolobated lungs)
  • Cystic hygroma
Last updated: 7/16/2009

What causes HEM?

HEM is associated with mutations (changes) in the lamin B receptor (LBR) gene located on chromosome 1, specifically at 1q42.1.[3][2]  Each person has two copies of the LBR gene - one inherited from mom and the other from dad. People who have two mutated copies of the LBR gene have HEM; thus, the condition is said to be inherited in an autosomal recessive pattern. The presence of two mutated copies of the LBR gene may affect the structure of the nucleus of the cell as well.[4]
Last updated: 7/16/2009

How is HEM diagnosed?

Establishing a diagnosis of HEM prenatally can be difficult and may require the interaction between a perinatologist, geneticist, and fetal/neonatal pathologist. Clinical examination, radiographs, genetic testing, and autopsy may be performed in order to establish a diagnosis of HEM.[2][1]
Last updated: 7/16/2009

Is carrier testing available for people who have other family members who are carriers or who have been affected with HEM?

Yes. Carrier testing is available for HEM. Clinical laboratories offering carrier testing for HEM are listed through and Orphanet. (Please note: Most laboratories do not accept direct contact from patients and their families; thererfore, you may have to work with a health care provider such as a genetics professional to learn more and coordinate testing.)
Last updated: 7/16/2009

How can my family members determine their chances of having a child with HEM?

To determine one's chances of having a child with HEM, we recommend scheduling a genetics consultation with a genetics professional. Genetics clinics are a source of information for individuals and families regarding genetic diagnosis, natural history, treatment, mode of inheritance, and genetic risks to other family members. To find a genetics clinic, we recommend that you contact your primary doctor for a referral.

The following online resources can also help you find a genetics professional in your community:

  * GeneTests - A searchable directory of US and international genetics and prenatal diagnosis clinics. Go to the following link and click on 'Clinic Directory' to find a genetic service close to you.

  * ResourceLink - A database of genetics counseling services, searchable by location, name, institution, type of practice, or specialty. Hosted by the National Society of Genetic Counselors.

  * Genetic Centers, Clinics, and Departments - A comprehensive resource list for genetic counseling, including links to genetic centers and clinics, associations, and university genetics departments. Hosted by the University of Kansas Medical Center.

Last updated: 7/16/2009

What is the prognosis for HEM?

All cases of HEM reported to date in the medical literature have resulted in death in utero.[2]
Last updated: 7/16/2009

Are there truly only a handful of cases of HEM?

According to the most recent published article on HEM we found by Konstantinidou et al. (2008), there have only been eight reported cases.[2]
Last updated: 7/16/2009

Has this horrible condition not captured the eye of the research community?

According to and Orphanet, there are several laboratories that are conducting research on HEM. Click on the links below to learn more. Addiitonally, an International Skeletal Dysplasia Registry was established in 1970 to collect information for research into the diagnosis, management and causes of the skeletal dysplasias.  
Last updated: 7/16/2009

  • Madazli R, Aksoy F, Ocak V, Atasu T. Detailed ultrasonographic findings in Greenberg dysplasia. Prenat Diagn. 2001;
  • Konstantinidou A, Karadimas C, Waterham HR, Superti-Furga A, Kaminopetros P, Grigoriadou M et al. Pathologic, radiographic and molecular findings in three fetuses diagnosed with HEM/Greenberg skeletal dysplasia. Prenat Diagnosis. 2008;
  • LBR - lamin B receptor. Genetics Home Reference. Accessed 7/15/2009.
  • Worman HJ, Bonne G. "Laminopathies": A wide spectrum of human diseases. Experimental Cell Research. 2007;