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Disease Profile

Greenberg dysplasia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Antenatal

ICD-10

Q77.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Hydrops-ectopic calcification-motheaten syndrome; Skeletal dysplasia, Greenberg type; HEM;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases

Summary

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.

Symptoms

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.

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.

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
Abnormal scapula morphology
Abnormality of the shoulder blade
0000782
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 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

Cause

Greenberg dysplasia is associated with mutations (changes) in both copies of the lamin B receptor (LBR) gene located on chromosome 1.[3]

Diagnosis

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]

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.

    Organizations

    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

      Learn more

      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.

          References

          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. https://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;

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