Rare Endocrinology News

Disease Profile

Wolf-Hirschhorn 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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Neonatal

ICD-10

Q93.3

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)

WHS; Wolf syndrome; Chromosome 4p syndrome;

Categories

Chromosome Disorders; Congenital and Genetic Diseases; Digestive Diseases;

Summary

Wolf-Hirschhorn syndrome (WHS) is a genetic disorder that affects many parts of the body. The major features include a characteristic facial appearance, delayed growth and development, intellectual disability, low muscle tone (hypotonia), and seizures. Other features may include skeletal abnormalities, congenital heart defects, hearing loss, urinary tract malformations, and/or structural brain abnormalities. WHS is caused by a missing piece (deletion) of genetic material near the end of the short (p) arm of chromosome 4 (written as 4p-). The size of the deletion varies among people with WHS, and studies suggest larger deletions tend to result in more severe features. Most cases of WHS are not inherited, but some cases are inherited from a parent who does not have WHS.[1][2] Treatment depends on the symptoms.

Symptoms

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.

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.
    Medical Terms Other Names
    Learn More:
    HPO ID
    80%-99% of people have these symptoms
    Ataxia
    0001251
    Decreased fetal movement
    Less than 10 fetal movements in 12 hours
    0001558
    Decreased muscle mass
    0003199
    Dolichocephaly
    Long, narrow head
    Tall and narrow skull

    [ more ]

    0000268
    Downslanted palpebral fissures
    Downward slanting of the opening between the eyelids
    0000494
    Downturned corners of mouth
    Downturned corners of the mouth
    Downturned mouth

    [ more ]

    0002714
    Epicanthus
    Eye folds
    Prominent eye folds

    [ more ]

    0000286
    Failure to thrive
    Faltering weight
    Weight faltering

    [ more ]

    0001508
    Frontal bossing
    0002007
    Generalized hypotonia
    Decreased muscle tone
    Low muscle tone

    [ more ]

    0001290
    Global developmental delay
    0001263
    High anterior hairline
    High frontal hairline
    0009890
    High forehead
    0000348
    Highly arched eyebrow
    Arched eyebrows
    Broad, arched eyebrows
    High, rounded eyebrows
    High-arched eyebrows
    Thick, flared eyebrows

    [ more ]

    0002553
    Hypertelorism
    Wide-set eyes
    Widely spaced eyes

    [ more ]

    0000316
    Hypodontia
    Failure of development of between one and six teeth
    0000668
    Hypospadias
    0000047
    Intellectual disability, severe
    Early and severe mental retardation
    Mental retardation, severe
    Severe mental retardation

    [ more ]

    0010864
    Intrauterine growth retardation
    Prenatal growth deficiency
    Prenatal growth retardation

    [ more ]

    0001511
    Low posterior hairline
    Low hairline at back of neck
    0002162
    Low-set, posteriorly rotated ears
    0000368
    Microcephaly
    Abnormally small skull
    Decreased circumference of cranium
    Decreased size of skull
    Reduced head circumference
    Small head circumference

    [ more ]

    0000252
    Micrognathia
    Little lower jaw
    Small jaw
    Small lower jaw

    [ more ]

    0000347
    Microtia
    Small ears
    Underdeveloped ears

    [ more ]

    0008551
    Muscular hypotonia
    Low or weak muscle tone
    0001252
    Seizure
    0001250
    Short philtrum
    0000322
    Small for gestational age
    Birth weight less than 10th percentile
    Low birth weight

    [ more ]

    0001518
    Wide nasal bridge
    Broad nasal bridge
    Broad nasal root
    Broadened nasal bridge
    Increased breadth of bridge of nose
    Increased breadth of nasal bridge
    Increased width of bridge of nose
    Widened nasal bridge
    Increased width of nasal bridge
    Nasal bridge broad
    Wide bridge of nose

    [ more ]

    0000431
    30%-79% of people have these symptoms
    Abnormal form of the vertebral bodies
    0003312
    Abnormal heart valve morphology
    0001654
    Abnormality of the kidney
    Abnormal kidney
    0000077
    Abnormality of the pinna
    Abnormally shaped ears
    Auricular malformation
    Deformed ears
    Malformed ears

    [ more ]

    0000377
    Aplasia cutis congenita of scalp
    0007385
    Aplasia/Hypoplasia of the lungs
    Absent/small lungs
    Absent/underdeveloped lungs

    [ more ]

    0006703
    Arachnodactyly
    Long slender fingers
    Spider fingers

    [ more ]

    0001166
    Atrial septal defect
    An opening in the wall separating the top two chambers of the heart
    Hole in heart wall separating two upper heart chambers

    [ more ]

    0001631
    Calvarial skull defect
    Cranial defect
    Skull defect

    [ more ]

    0001362
    Cleft upper lip
    Harelip
    0000204
    Congenital diaphragmatic hernia
    0000776
    Convex nasal ridge
    Beaked nose
    Beaklike protrusion
    Hooked nose
    Polly beak nasal deformity

    [ more ]

    0000444
    Craniofacial asymmetry
    0004484
    Cryptorchidism
    Undescended testes
    Undescended testis

    [ more ]

    0000028
    Delayed skeletal maturation
    Delayed bone maturation
    Delayed skeletal development

    [ more ]

    0002750
    Hearing impairment
    Deafness
    Hearing defect

    [ more ]

    0000365
    Hemangioma
    Strawberry mark
    0001028
    Hypoplastic pubic rami
    0008830
    Iris coloboma
    Cat eye
    0000612
    Kyphosis
    Hunched back
    Round back

    [ more ]

    0002808
    Nystagmus
    Involuntary, rapid, rhythmic eye movements
    0000639
    Optic atrophy
    0000648
    Preauricular pit
    Pit in front of the ear
    0004467
    Preauricular skin tag
    0000384
    Preaxial hand polydactyly
    Extra thumb
    0001177
    Prominent glabella
    Prominent area between the eyebrows
    Protruding area between the eyebrows

    [ more ]

    Conditions with similar signs and symptoms from Orphanet
    Differential diagnosis includes many syndromes displaying growth failure, intellectual disability and/or facial dysmorphism such as Seckel, CHARGE, Smith-Lemli-Opitz, Opitz G/BBB, Williams, Rett, Angelman and Smith-Magenis syndromes (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

      • The 4pSupport Group offers information on Wolf-Hirschhorn syndrome.
      • Genetics Home Reference (GHR) contains information on Wolf-Hirschhorn 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

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • 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 Wolf-Hirschhorn syndrome. Click on the link to view a sample search on this topic.

          References

          1. Wolf-Hirschhorn syndrome. Genetics Home Reference Website. April 2012; https://ghr.nlm.nih.gov/condition/wolf-hirschhorn-syndrome.
          2. Battaglia A, Carey JC, South ST & Wright TJ. Wolf-Hirschhorn Syndrome. GeneReviews. 2015; https://www.ncbi.nlm.nih.gov/books/NBK1183/.
          3. General 4pInfo. 4pSupport Group. 2015; https://4p-supportgroup.org/general-info/.
          4. What is WHS?. Wolf Hirschhorn Syndrome Trust. https://www.whs4pminus.co.uk/what-is-this/.

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