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Disease Profile

Schinzel Giedion syndrome

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

Q87.0

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.

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)

Schinzel Giedion midface-retraction syndrome; SGS; Schinzel-Giedion syndrome

Categories

Congenital and Genetic Diseases; Kidney and Urinary Diseases; Musculoskeletal Diseases;

Summary

Schinzel Giedion syndrome (SGS) is a rare, severe condition that is present from birth and affects many parts of the body. Features of SGS include severe intellectual disability; a distinctive facial appearance; excessive hair growth (hypertrichosis); and various birth defects that may affect the skeletal system, genitourinary system; kidneys; and heart. Affected children usually do not survive beyond a few years after birth.[1] SGS is caused by a mutation in the SETBP1 gene. The mutation is not inherited from a parent, but occurs for the first time in the affected child (a de novo mutation).[2] Treatment is based on symptoms and consists of palliative care.[3]

Symptoms

The signs and symptoms of Schinzel Giedion syndrome (SGS) are present from birth (congenital). The specific features can vary among affected children, but are generally severe. Recurrent infections and respiratory failure are common, and most children with SGS do not live beyond a few years after birth.[1]

Features in children with SGS may include:

  • a distinctive facial appearance including a prominent forehead; "flatness" of the middle part of the face (midface retraction); and a short upturned nose[3]
  • hydronephrosis
  • severe developmental delay and intellectual disability[3][1]
  • skeletal (bone) malformations such as short limbs; valgus or varus foot deformity (the foot is twisted outward or inward, respectively); skull abnormalities; or broad ribs[3][1]
  • genitourinary abnormalities such as undescended testicle(s); abnormally small penis; hypospadias; small uterus; underdeveloped inner and outer labia (folds) of the vagina; or displaced anus[3]
  • heart defects such as septal defects (affecting the dividing walls of the heart); valve abnormalities; hypoplastic ventricles (underdeveloped bottom chambers of the heart) or patent ductus arteriosus[3]
  • seizures[3]
  • visual or hearing impairment[3]
  • increased risk of tumors[3]
  • excessive hair growth (hypertrichosis)[3]
  • nail abnormalities[3]

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.

Cause

Schinzel Giedion syndrome (SGS) is caused by having a mutation in one copy of the SETBP1 gene. The mutation is not inherited from a parent it occurs for the first time in affected people.[3][2] This is called a de novo mutation. There is nothing either parent can do, or not do, before or during a pregnancy to cause a child to have SGS.

The SETBP1 gene gives the body instructions to make a protein (called SET binding protein 1), which is present in cells throughout the body.[4] However, to our knowledge, the job of this protein is poorly understood and it is not yet known why mutations in this particular gene cause the features of SGS.

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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.
    Medical Terms Other Names
    Learn More:
    HPO ID
    80%-99% of people have these symptoms
    Broad forehead
    Increased width of the forehead
    Wide forehead

    [ more ]

    0000337
    Broad nasal tip
    Broad tip of nose
    Broad, upturned nose
    Increased breadth of nasal tip
    Increased breadth of tip of nose
    Increased width of nasal tip
    Increased width of tip of nose
    Nasal tip, broad
    Nasal tip, wide
    Wide tip of nose

    [ more ]

    0000455
    Frontal bossing
    0002007
    Midface retrusion
    Decreased size of midface
    Midface deficiency
    Underdevelopment of midface

    [ more ]

    0011800
    Profound global developmental delay
    0012736
    Short nose
    Decreased length of nose
    Shortened nose

    [ more ]

    0003196
    30%-79% of people have these symptoms
    Abnormal heart morphology
    Abnormality of the heart
    Abnormally shaped heart
    Heart defect

    [ more ]

    0001627
    Abnormality of the helix
    0011039
    Broad ribs
    Wide ribs
    0000885
    Facial hemangioma
    0000329
    Failure to thrive in infancy
    Faltering weight in infancy
    Weight faltering in infancy

    [ more ]

    0001531
    Generalized hypertrichosis
    0004554
    Hydronephrosis
    0000126
    Hypertelorism
    Wide-set eyes
    Widely spaced eyes

    [ more ]

    0000316
    Hypoplasia of the corpus callosum
    Underdevelopment of part of brain called corpus callosum
    0002079
    Low-set ears
    Low set ears
    Lowset ears

    [ more ]

    0000369
    Macroglossia
    Abnormally large tongue
    Increased size of tongue
    Large tongue

    [ more ]

    0000158
    Narrow forehead
    Decreased width of the forehead
    0000341
    Shallow orbits
    Decreased depth of eye sockets
    Shallow eye sockets

    [ more ]

    0000586
    Short distal phalanx of finger
    Short outermost finger bone
    0009882
    Short neck
    Decreased length of neck
    0000470
    Ventriculomegaly
    0002119
    Visual impairment
    Impaired vision
    Loss of eyesight
    Poor vision

    [ more ]

    0000505
    Wide anterior fontanel
    Wider-than-typical soft spot of skull
    0000260
    Wide mouth
    Broad mouth
    Large mouth

    [ more ]

    0000154
    5%-29% of people have these symptoms
    Abnormal clavicle morphology
    Abnormal collarbone
    0000889
    Abnormal cochlea morphology
    0000375
    Abnormality of the gingiva
    Abnormality of the gums
    0000168
    Abnormality of the stapes
    0008628
    Aganglionic megacolon
    Enlarged colon lacking nerve cells
    0002251
    Alacrima
    Absence of tears in the eyes
    Absent tear secretion

    [ more ]

    0000522
    Annular pancreas
    0001734
    Anteriorly placed anus
    0001545
    Arnold-Chiari type I malformation
    0007099
    Broad alveolar ridges
    0000187
    Cerebral cortical atrophy
    Decrease in size of the outer layer of the brain due to loss of brain cells
    0002120
    Choanal stenosis
    Narrowing of the rear opening of the nasal cavity
    0000452
    Choroid plexus cyst
    0002190
    Delayed eruption of teeth
    Delayed eruption
    Delayed teeth eruption
    Delayed tooth eruption
    Eruption, delayed
    Late eruption of teeth
    Late tooth eruption

    [ more ]

    0000684
    High palate
    Elevated palate
    Increased palatal height

    [ more ]

    0000218
    Hypoplastic pubic bone
    0003173
    Infantile sensorineural hearing impairment
    0008610
    Kyphoscoliosis
    0002751
    Micrognathia
    Little lower jaw
    Small jaw
    Small lower jaw

    [ more ]

    0000347
    Neural tube defect
    0045005
    Overlapping fingers
    0010557
    Overlapping toe
    Overlapping toes
    Overriding toes

    [ more ]

    0001845
    Pulmonary hypoplasia
    Small lung
    Underdeveloped lung

    [ more ]

    0002089
    Respiratory distress
    Breathing difficulties
    Difficulty breathing

    [ more ]

    0002098
    Retrognathia
    Receding chin
    Receding lower jaw
    Weak chin
    Weak jaw

    [ more ]

    0000278
    Sclerosis of skull base
    Dense bone of skull base
    0002694
    Short 1st metacarpal
    Shortened 1st long bone of hand
    0010034
    Conditions with similar signs and symptoms from Orphanet
    Other conditions with the distinctive midface retraction that could be considered in the differential diagnosis include fetal hydantoin, fetal warfarin syndromes, Zellweger syndrome, mucopolysaccharidosis, gangliosidosis, and rhizomelic chondrodysplasia punctata, as well as congenital hypothyroidism (see these terms).
    Visit the Orphanet disease page for more information.

    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

      • MedlinePlus Genetics contains information on Schinzel Giedion syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        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 Schinzel Giedion syndrome. Click on the link to view a sample search on this topic.

          References

          1. Herenger Y et. al. Long term follow up of two independent patients with Schinzel-Giedion carrying SETBP1 mutations. Eur J Med Genet. September, 2015; 58(9):479-487.
          2. Marla J. F. O'Neill. SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME. OMIM. May 12, 2011; https://www.omim.org/entry/269150.
          3. Albert Schinzel. Schinzel-Giedion syndrome. Orphanet. April, 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=798.
          4. SETBP1. Genetics Home Reference. January, 2012; https://ghr.nlm.nih.gov/gene/SETBP1.

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