National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Greenberg dysplasia


Other Names:
Hydrops-ectopic calcification-motheaten syndrome; Skeletal dysplasia, Greenberg type; HEM; Hydrops-ectopic calcification-motheaten syndrome; Skeletal dysplasia, Greenberg type; HEM; Hydrops, Ectopic calcification, Moth-eaten skeletal dysplasia; HEM dysplasia; HEM/Greenberg dysplasia; Greenberg skeletal dysplasia; Autosomal recessive lethal chondrodystrophy with congenital hydrops See More
Categories:
Greenberg dysplasia is a very severe disorder that that affects the bones.[1] It is called a skeletal dysplasia because the bones do not develop properly. This condition is sometimes called HEM based on the main features of Hydrops fetalis, Ectopic calcifications, and "Moth-eaten" appearance of the skeleton. Greenberg dysplasia is an autosomal recessive condition caused by a mutation in the lamin B receptor (LBR) gene.[2] Because of the very severe symptoms of Greenberg dysplasia, fetuses with this condition do not survive until birth. 
Last updated: 8/24/2016
Greenberg dysplasia causes problems when the bones are developing in a fetus. Bones have a spotted, moth-eaten look when seen on an X-ray. Another sign is the abnormal build up of calcium in soft tissues of the body (ectopic calcification). The legs and arms are severely shortened (micromelia) and there may be extra fingers or toes (polydactyly). The fetus may also develop severe swelling all over the body called hydrops fetalis.
Last updated: 8/24/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 83 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal leukocyte morphology 0001881
Abnormal pelvis bone ossification 0009106
Abnormally ossified vertebrae
Abnormal bone maturation of vertebra
0100569
Anterior rib punctate calcifications 0006619
Brachydactyly
Short fingers or toes
0001156
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Micromelia
Smaller or shorter than typical limbs
0002983
Platyspondyly
Flattened vertebrae
0000926
Rhizomelia
Disproportionately short upper portion of limb
0008905
Severe short-limb dwarfism 0008890
30%-79% of people have these symptoms
Calvarial skull defect
Cranial defect
Skull defect
[ more ] 		0001362
Decreased skull ossification
Decreased bone formation of skull
0004331
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Narrow chest
Low chest circumference
Narrow shoulders
[ more ] 		0000774
Preeclampsia 0100602
Percent of people who have these symptoms is not available through HPO
11 pairs of ribs 0000878
Abnormal circulating cholesterol concentration
Abnormality of cholesterol metabolism
0003107
Abnormal foot bone ossification 0010675
Abnormal joint morphology
Abnormal shape of joints
Abnormality of the joints
Anomaly of the joints
[ more ] 		0001367
Abnormal lung lobation 0002101
Abnormal ossification involving the femoral head and neck 0009107
Abnormality of the calcaneus
Abnormal heel bone
0008364
Abnormality of the orbital region
Abnormality of the eye region
Abnormality of the region around the eyes
[ more ] 		0000315
Abnormality of the scapula
Abnormality of the shoulder blade
0000782
Abnormality of the vertebral spinous processes 0008516
Absent or minimally ossified vertebral bodies 0004599
Absent toenail 0001802
Autosomal recessive inheritance 0000007
Barrel-shaped chest
Barrel chest
0001552
Bone marrow hypocellularity
Bone marrow failure
0005528
Bowing of the long bones
Bowed long bones
Bowing of long bones
[ more ] 		0006487
Broad palm
Broad hand
Broad hands
Wide palm
[ more ] 		0001169
Cardiomegaly
Enlarged heart
Increased heart size
[ more ] 		0001640
Cystic hygroma 0000476
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Diaphyseal thickening
Thickening of shaft or central part of long bones
0005019
Disproportionate short-limb short stature
Short limb dwarfism, disproportionate
Short-limbed dwarfism
[ more ] 		0008873
Epiphyseal stippling
Speckled calcifications in end part of bone
0010655
Extramedullary hematopoiesis 0001978
Flared metaphysis
Flared wide portion of long bone
0003015
Hepatic calcification 0006559
Hepatomegaly
Enlarged liver
0002240
Hepatosplenomegaly
Enlarged liver and spleen
0001433
High forehead 0000348
Horizontal sacrum 0003440
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion
[ more ] 		0000327
Hypoplastic fingernail
Small fingernail
Underdeveloped fingernail
[ more ] 		0001804
Hypoplastic vertebral bodies
Underdeveloped back bones
0008479
Intestinal malrotation 0002566
Laryngeal calcification 0008754
Lethal skeletal dysplasia
Lethal dwarfism identifiable at birth
0005716
Long clavicles
Long collarbone
0000890
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Malar flattening
Zygomatic flattening
0000272
Mesomelia
Disproportionately short middle portion of limb
0003027
Metaphyseal cupping 0003021
Misalignment of teeth
Abnormal dental position
Abnormal teeth spacing
Abnormality of alignment of teeth
Abnormality of teeth spacing
Crooked teeth
Malaligned teeth
Malposition of teeth
Malpositioned teeth
[ more ] 		0000692
Multiple prenatal fractures
Multiple fractures present at birth
Multiple fractures, present at birth
Numerous multiple fractures present at birth
Numerous multiple fractures that are present at birth
[ more ] 		0005855
Neonatal death
Neonatal lethal
0003811
Nonimmune hydrops fetalis 0001790
Omphalocele 0001539
Pancreatic islet-cell hyperplasia 0004510
Patchy variation in bone mineral density
Patchy increased and decreased bone mineral density
0010659
Pleural effusion
Fluid around lungs
0002202
Polyhydramnios
High levels of amniotic fluid
0001561
Postaxial foot polydactyly
Extra toe attached near the little toe
0001830
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger
[ more ] 		0001162
Pulmonary hypoplasia
Small lung
Underdeveloped lung
[ more ] 		0002089
Punctate vertebral calcifications 0008420
Sandal gap
Gap between 1st and 2nd toes
Gap between first and second toe
Increased space between first and second toes
Sandal gap between first and second toes
Wide space between 1st, 2nd toes
Wide space between first and second toes
Wide-spaced big toe
Widely spaced 1st-2nd toes
Widely spaced first and second toes
Widened gap 1st-2nd toes
Widened gap first and second toe
[ more ] 		0001852
Sclerosis of skull base
Dense bone of skull base
0002694
Severe hydrops fetalis 0005099
Short diaphyses
Short shaft of long bone
0000941
Short phalanx of finger
Short finger bones
0009803
Short ribs 0000773
Sternal punctate calcifications 0006637
Stillbirth
Stillborn
0003826
Supernumerary vertebral ossification centers 0004598
Tracheal calcification 0002787
Ulnar deviation of the hand 0009487
Showing of 83 |
Last updated: 7/1/2020
Greenberg dysplasia is associated with mutations (changes) in both copies of the lamin B receptor (LBR) gene located on chromosome 1.[3]

Last updated: 8/24/2016
Establishing a diagnosis of Greenberg dysplasia can be difficult. Several types of doctors usually work together, such as a maternal-fetal medicine specialist, clinical geneticist, and a pathologist. A prenatal ultrasound usually detects the bone abnormalities and swelling of the body (hydrops fetalis) that develop in this condition. Clinical examination, X-rays, genetic testing, and autopsy may also be performed in order to diagnose Greenberg dysplasia.[4][5]
Last updated: 8/24/2016

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Greenberg dysplasia is a very severe condition that causes a fetus to not survive to birth.[4]
Last updated: 8/24/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Greenberg dysplasia should be considered in differential diagnosis of cases with severe fetal hydrops (see this term) and phokomelia on antenatal sonography.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Greenberg dysplasia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Greenberg dysplasia. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Greenberg dysplasia:
    International Skeletal Dysplasia Registry (ISDR)
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Greenberg dysplasia. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Since my daughter passed from Greenberg dysplasia, I have checked the leading publications for news of this condition. 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. See answer


  1. Greenberg dysplasia. Genetics Home Reference. February 2012; https://ghr.nlm.nih.gov/condition/greenberg-dysplasia.
  2. Clayton P et. al. Mutations causing Greenberg dysplasia but not Pelger anomaly uncouple enzymatic from structural functions of a nuclear membrane protein. Nucleus. Jul-Aug 2010; 1(4):354-366. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3027044/.
  3. LBR - lamin B receptor. Genetics Home Reference. http://ghr.nlm.nih.gov/gene=lbr#location. Accessed 7/15/2009.
  4. 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; https://www.ncbi.nlm.nih.gov/pubmed/18382993.
  5. Madazli R, Aksoy F, Ocak V, Atasu T. Detailed ultrasonographic findings in Greenberg dysplasia. Prenat Diagn. 2001;