Wolf-Hirschhorn syndrome

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Other Names:

WHS; Wolf syndrome; Chromosome 4p syndrome; WHS; Wolf syndrome; Chromosome 4p syndrome; Microcephaly, IUGR, Hypertelorism, Ptosis, iris coloboma, hooked nose, external ear dysplasia, psychomotor retardation; 4p syndrome; Distal deletion 4p; 4p- syndrome; Distal monosomy 4p; Telomeric deletion 4p; Wittwer syndrome; Pitt-Rogers-Danks syndrome See More

Categories:

Chromosome Disorders; Congenital and Genetic Diseases; Digestive Diseases; Chromosome Disorders; Congenital and Genetic Diseases; Digestive Diseases; Ear, Nose, and Throat Diseases; Eye diseases; Lung Diseases; Nervous System Diseases See More

Summary 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.

Last updated: 4/28/2017

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.

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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 Thick, flared eyebrows High-arched eyebrows High, rounded eyebrows Broad, arched 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 size of skull Decreased circumference of cranium Small head circumference Reduced head circumference [ more ]	0000252
Micrognathia	Little lower jaw Small lower jaw Small 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 root Increased breadth of bridge of nose Broadened nasal bridge Nasal bridge broad Increased width of nasal bridge Increased width of bridge of nose Increased breadth of nasal bridge Broad nasal bridge Widened nasal bridge 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	Hole in heart wall separating two upper heart chambers An opening in the wall separating the top two chambers of the heart [ 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 ]	0002057
Proptosis	Bulging eye Eyeballs bulging out Prominent eyes Prominent globes Protruding eyes [ more ]	0000520
Ptosis	Drooping upper eyelid	0000508
Rib fusion	Fused ribs	0000902
Rib segmentation abnormalities		0006655
Rieger anomaly		0000558
Sacral dimple	Spinal dimple	0000960
Scoliosis		0002650
Severe postnatal growth retardation	Marked growth retardation Severe growth delay in children Severe postnatal growth failure [ more ]	0008850
Short hallux	Short big toe	0010109
Short stature	Decreased body height Small stature [ more ]	0004322
Short thumb	Short thumbs Small thumbs [ more ]	0009778
Short upper lip	Decreased height of upper lip Decreased vertical length of upper lip Shortening of upper lip [ more ]	0000188
Split hand	Claw hand deformities Claw hand Claw-hand deformities Claw hands Split-hand [ more ]	0001171
Stenosis of the external auditory canal	Narrowing of passageway from outer ear to middle ear	0000402
Stereotypy	Repetitive movements Repetitive or self-injurious behavior [ more ]	0000733
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Talipes equinovarus	Club feet Club foot Clubfeet Clubfoot [ more ]	0001762
Tethered cord		0002144
5%-29% of people have these symptoms
Abdominal situs inversus		0003363
Abnormality of movement	Movement disorder Unusual movement [ more ]	0100022
Abnormality of the gallbladder		0005264
Agenesis of corpus callosum		0001274
Aplasia of the uterus	Absent uterus uterus absent [ more ]	0000151
Aplasia/Hypoplasia of the cerebellum	Absent/small cerebellum Absent/underdeveloped cerebellum [ more ]	0007360
Aplasia/Hypoplasia of the nipples	Absent/small nipples Absent/underdeveloped nipples [ more ]	0006709
Biliary tract abnormality		0001080
Chronic otitis media	Chronic infections of the middle ear	0000389
Cleft palate	Cleft roof of mouth	0000175
Disproportionate tall stature		0001519
Hip dysplasia		0001385
Hydrocephalus	Too much cerebrospinal fluid in the brain	0000238
Megalocornea	Enlarged cornea	0000485
Osteoporosis		0000939
Preaxial foot polydactyly		0001841
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Retinopathy	Noninflammatory retina disease	0000488
Sclerocornea	Hardening of skin and connective tissue	0000647
Single transverse palmar crease		0000954
Webbed neck	Neck webbing	0000465
1%-4% of people have these symptoms
Conductive hearing impairment	Conductive deafness Conductive hearing loss [ more ]	0000405
EEG abnormality		0002353
Immunodeficiency	Decreased immune function	0002721
Sensorineural hearing impairment		0000407
Percent of people who have these symptoms is not available through HPO
Abnormal sternal ossification	Abnormal maturation of breastbone	0011863
Absent septum pellucidum		0001331
Accessory spleen		0001747
Autosomal dominant inheritance		0000006
Cavum septum pellucidum		0002389
Ectopia pupillae	Displaced pupil	0009918
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Hip dislocation	Dislocated hips Dislocation of hip [ more ]	0002827
Hyperconvex fingernails		0001812
Malrotation of small bowel		0004794
Metatarsus adductus	Front half of foot turns inward	0001840
Periventricular cysts		0007109
Precocious puberty	Early onset of puberty Early puberty [ more ]	0000826
Pseudoepiphyses of the metacarpals		0009193
Radioulnar synostosis	Fused forearm bones	0002974
Sporadic	No previous family history	0003745
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629
Ventriculomegaly		0002119
Vertebral fusion	Spinal fusion	0002948

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 1/1/2021

Do you have updated information on this disease? We want to hear from you.

Inheritance Inheritance

Many cases of Wolf-Hirschhorn syndrome (WHS) (about 50-60%) are not inherited from a parent and are caused by a new (de novo) deletion of a region of chromosome 4 (called 4p16) that occurs for the first time in the person with WHS. In about 40-45% of cases, the person with WHS has an unbalanced translocation with both a deletion on chromosome 4 and an extra piece (trisomy) of part of another chromosome. In these cases, the unbalanced translocation may be de novo, or inherited from a parent who carries a balanced rearrangement (when parts of chromosomes are rearranged but there is no extra or missing genetic material).^[2]

Risks to family members and their children depend on whether the person with WHS has the syndrome due to a de novo deletion or an unbalanced translocation.^[2]

Last updated: 4/28/2017

Diagnosis 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.

Prognosis Prognosis

The long-term outlook (prognosis) for people with Wolf-Hirschhorn syndrome (WHS) depends on the specific features present and the severity of those features. The average life expectancy is unknown. Muscle weakness may increase the risk of having chest infections and ultimately may reduce the life expectancy. Many people, in the absence of severe heart defects, chest infections, and uncontrollable seizures, survive into adulthood.^[3]^[4]

Last updated: 4/28/2017

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

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
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.

Research Research

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

Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Organizations 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

4p- Support Group
131 Green Cook Road
Sunbury, OH 43074
E-mail: membership@4p-supportgroup.org
Website: http://www.4p-supportgroup.org/
Chromosome Disorder Outreach (CDO)
PO Box 724
Boca Raton, FL 33429
Telephone: +1-561-395-4252
E-mail: https://chromodisorder.org/contact/
Website: https://chromodisorder.org/
Unique – Rare Chromosome Disorder Support Group
G1, The Stables
Station Road West
Surrey
RH8 9EE
United Kingdom
Telephone: +44 (0)1883 723356
E-mail: info@rarechromo.org
Website: https://www.rarechromo.org/
Wolf-Hirschhorn Syndrome Trust (UK)
Telephone: 0845-603-5338
E-mail: enquiries@whs4pminus.co.uk
Website: http://www.whs4pminus.co.uk/

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More 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 4p- Support 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.

GARD Answers GARD Answers

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

My step-daughter carries Wolf-Hirschhorn syndrome. Should my son be tested? He is 18. He is a half brother. See answer
My 37-year-old daughter has Wolf-Hirschhorn syndrome. As she has gotten older, her behaviors have gotten worse, which is stressful and frustrating. Her behaviors include alternating periods of aggression, excitement, depression, apathy, antisocial behavior, and anger. She also has sudden mood swings accompanied by bizarre behaviors such as pulling people's hair and clothes and swiping things of a table. Can you tell me if these are recognized symptoms of this syndrome? If so, can one do anything about them? See answer
What is the life expectancy for someone with Wolf-Hirschhorn syndrome? See answer
My sister has two children that have been diagnosed with Wolf-Hirschhorn Syndrome. How common is it for a person to have more than one child with the syndrome? I am interested in getting a genetic test to see if I am a carrier. Will the test be covered by my insurance? How much do they generally cost? See answer