Wolf-Hirschhorn Syndrome

Wolf Hirschhorn Syndrome Definition

Wolf Hirschhorn Syndrome is a genetic disorder develops due to partial deletion of chromosome 4 at the short arm. The resultant of this leads to growth retardation in both prenatal and postnatal stages of the fetus.

The characteristic features include a typical craniofacial appearance with multiple birth defects, including psychomotor development impairment, cognitive disability, hypotonia, and seizures. [1]

Wolf Hirschhorn Syndrome symptoms


A partial deletion of chromosome 4p (p denotes short arm of the chromosome) is a genetic disorder that causes Wolf-Hirschhorn Syndrome. Approximately 50% sufferers follow a novel type of pure deletion of 4p16. The remaining sufferers, almost 40-45% patients comprise an abnormal DNA sequence (unbalanced translocation) with both a missing of 4p and a partial trisomy of a different chromosome arm. The unbalanced DNA sequence (translocation) may be novel in sufferer chromosomal arrangement or hereditary unique balanced rearrangement. The rest 5 to 10% patients have other intricated rescheduling of DNA sequence and cause deletion of 4p16.3 chromosomes. [2,3,4]

Wolf Hirschhorn Syndrome


Wolf Hirschhorn Syndrome is unique genetic arrangement due to the varied reason of cause, therefore the sign and symptoms vary within a wide range. All the mentioned sign and symptoms may not prominent for all.

Wolf Hirschhorn Syndrome adultss

The symptomatic analysis is important for Wolf Hirschhorn Syndrome because this assists in the management of the syndrome depending upon the requirements of the patients and provide supportive care accordingly. The included sign and symptoms of Wolf Hirschhorn Syndrome are as follows:

  • Prenatal slow growth
  • Postnatal insufficient growth
  • Head circumference smaller than the normal infant and/or child
  • Crying intensity and frequency is less than the normal
  • Hypotonia (reduce muscular tone)
  • Epileptic attacks
  • Prominent developmental disturbance
  • Delayed motor skill development
  • Strabismus or cross eyes
  • Hypertelorism or wide space between the two eye orbits
  • Ptosis or droopy eyelids
  • Epicanthal folds or skin of the eye corner is folded
  • Cleft lip
  • Cleft palate
  • Upper lip is narrow
  • Micrognathia or Small sized chin
  • Cranial irregularity or asymmetric skull
  • Hand and pelvis bone are underdeveloped
  • Cardiac septal defect
  • Underdeveloped secondary sexual organs
  • Clubfoot
  • Fingerprints are not properly developed due to dermal ridges are not properly developed
  • Scoliosis(bend spine)
  • Immunodeficiency [4,5,6]


In suspected cases, the doctor usually prefers to conduct the diagnostic test at the prenatal phase. The prenatal tests are conducted for those, where one parent already identified by possessing a 4p16.3 chromosome rearrangement. [4]

The included test in prenatal diagnosis are:

  • Prenatal ultrasound scanning provides abnormal specific physical findings and karyotyping is followed for verification
  • Chorionic villus sampling or amniocentesis are used for chromosomal analysis
  • Umbilical blood sampling is required for rapid fetal karyotyping

Diagnostic tests are also continued at postnatal phase. The initial diagnosis is based on symptomatic analysis and followed by physical examination. The definite cases are identified by molecular genetics or cytogenetic analysis, genome-wide CMA (chromosomal microarray analysis) and FISH (fluorescence in situ hybridization). Among these tests, depends on upon physician choice the selected test is conducted for confirmation of the disease. Apart from these the following additional diagnostic tests are conducted:

  • The number and function analysis for immunoglobulin and T-cell to evaluate immunodeficiency.
  • Abnormality in EEG findings (Electroencephalography), which follow a typical seizure patterns. This finding is almost found in 90% affected patients
  • Atrial septal defect or ventricular septal defect may identify in Echocardiography testing
  • Urinary tract imaging
  • MRI and CT scan of the brain to identify the associated pathologic condition in the brain, e.g. findings of enlarged ventricles. [2,7]


Wolf Hirschhorn Syndrome is noncurable disease and treatment is based on supportive care. The foremost important treatment approach for patients suffering from Wolf Hirschhorn Syndrome are symptomatic management.

A team of multidisciplinary experts is required for management of the Wolf-Hirschhorn Syndrome. The planned treatment is to give support the patient in regards of mental growth retardation, delayed physical growth, and behavioral problems.

  • Valproic acid alone or in combination with ethosuximide is provided to control seizure attacks, though it is difficult to manage.
  • Feeding therapies are recommended for Wolf Hirschhorn Syndrome sufferers, as they often have a feeding problem.
  • Genetic counseling is also part of treatment approach, as there is a chance of inherited disease transmission from either of a parent.
  • Surgical repair is required for correction of different malformations, including cleft lip and palate
  • Different rehabilitation therapies, physiotherapies, education, social, or vocational services are also included in the treatment approach of Wolf Hirschhorn syndrome with the belief of this combined therapy can provide some benefits to the sufferers. [8,9]


The prognosis of Wolf Hirschhorn syndrome is not same for every case, following are the possible prognosis

  • Often consequences of Wolf Hirschhorn syndrome are stillbirth or fatality within the initial year.
  • If sufferer survives infancy period, they have delay, but steady developmental progress physically and mentally
  • Most of the children suffering from Wolf Hirschhorn syndrome have only two years of life span after birth, because of complication arises due to the presence of a cardiac problem, aspiration pneumonia, seizure attacks or other severe infection.
  • The risk of recurrence in negligible for Sporadic cases. [10]

Life Expectancy

The life expectancy is not same for every individual suffering from Wolf Hirschhorn Syndrome. The survival is very difficult in the infant stage. But if patient tolerates all the associated symptoms and survives then they can persist their life till their adult age. [8]


Wolf Hirschhorn Syndrome is non-curable disease, and some cases are inherited, therefore if any one partner is identified as a carrier of 4p16.3 chromosome rearrangement, then genetic counseling can be a preventive measure. [6]


  1. N L Shannon, E L Maltby, A S Rigby, O W J Quarrell; An epidemiological study of Wolf-Hirschhorn syndrome: life expectancy and cause of mortality; J Med Genet 2001;38:674-679 doi:10.1136/jmg.38.10.674
  2. Battaglia A, Carey JC; Seizure and EEG patterns in Wolf-Hirschhorn (4p-) syndrome. Brain Dev. 2005 Aug;27(5):362-4. Epub 2005 Apr 22.
  3. Wolf-Hirschhorn Syndrome, WHS; Online Mendelian Inheritance in Man (OMIM)
  4. Wolf-Hirschhorn Syndrome; wolfhirschhorn.org; Retrieve from: http://wolfhirschhorn.org/about-wolf-hirschhorn-syndrome/
  5. Paradowska-Stolarz AM; Wolf-Hirschhorn syndrome (WHS) – literature review on the features of the syndrome. Adv Clin Exp Med. 2014 May-Jun;23(3):485-9.
  6. Battaglia A, et al; Wolf-Hirschhorn Syndrome, Gene Reviews, April 2009
  7. Debost-Legrand A, Goumy C, Laurichesse-Delmas H, et al; Prenatal ultrasound findings observed in the Wolf-Hirschhorn syndrome: data from the registry of congenital malformations in Auvergne. Birth Defects Res A Clin Mol Teratol. 2013 Dec;97(12):806-11. doi: 10.1002/bdra.23194. Epub 2013 Nov 6.
  8. Dr. Agatino BATTAGLIA (2012); Wolf-Hirschhorn syndrome; http://www.orpha.net/consor4.01/www/cgi-bin/OC_Exp.php?lng=EN&Expert=280
  9. Wolf-Hirschhorn Syndrome; National Organization for Rare Disorders; https://rarediseases.org/rare-diseases/wolf-hirschhorn-syndrome/
  10. Dr Colin Tidy (2015); Wolf-Hirschhorn Syndrome; Retrieve from: http://patient.info/in/doctor/wolf-hirschhorn-syndrome-pro

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