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Wolf-Hirschhorn Syndrome Differential Diagnoses

  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Luis O Rohena, MD  more...
Updated: Feb 15, 2015

Diagnostic Considerations

These include the following:

  • Angelman syndrome: This is a neurogenetic disorder characterized by severe intellectual and developmental disability, sleep disturbance, seizures, jerky limb movements (especially hand flapping and a wide-based, stiff-legged gait), frequent laughter or smiling, and usually a happy demeanor; it is caused by chromosome deletion (de novo) of the maternally derived chromosome region 15q11-q13 (~70%), rare deletion due to unique chromosome 15 rearrangement within 15q11-q13 (< 1%), and UBE3A and other presumed single gene mutations (20-25%)
  • Smith-Magenis syndrome: This is a complex developmental disorder that consists of multiple congenital anomalies and intellectual disability caused by an interstitial deletion of chromosome 17p11.2
  • Duplication 4p syndrome: This syndrome is characterized by interstitial direct duplication of 4p (4p16.1-3), large low-set ears, microcephaly, a prominent glabella, broad nasal bridge, bulbous nose (often referred to as box nose), growth deficiency, severe mental retardation, seizures, scoliosis, fifth finger clinodactyly, flexion contractures, and hypospadias
  • Other autosomal monosomy syndromes and trisomy syndromes
  • Other multiple congenital anomalies and mental retardation syndromes
  • Pitt-Rogers-Danks syndrome (OMIM #262350): This is a rare disorder, presumed to have autosomal recessive inheritance, that is characterized by prenatal and postnatal growth retardation, microcephaly, characteristic facial appearance, seizures, unusual palmar creases, and developmental delay; microdeletion of chromosome band 4p16 has been reported; the syndrome is now considered to be a part of Wolf-Hirschhorn syndrome
  • Proximal 4p syndrome: This syndrome is characterized by deletion of the proximal half of chromosome arm 4p (4p11->4p15), moderate intellectual disability, normal height, short palpebral fissures, abnormal ears, large nose, broad hands, microcephaly, short fingers, and congenital heart defects
  • Seckel syndrome (OMIM #210600): This syndrome is also known as bird-headed dwarfism or microcephalic primordial dwarfism type I

Differential Diagnoses

Contributor Information and Disclosures

Harold Chen, MD, MS, FAAP, FACMG Professor, Department of Pediatrics, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lois J Starr, MD, FAAP Assistant Professor of Pediatrics, Clinical Geneticist, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center

Lois J Starr, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

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A child with Wolf-Hirschhorn syndrome. Note the characteristic dysmorphic facial features, including prominent glabella, hypertelorism, beaked nose, and frontal bossing, collectively described as "Greek warrior helmet" facies.
A fetus with Wolf-Hirschhorn syndrome. Note the presence of "Greek warrior helmet" facies.
The result of a fluorescence in situ hybridization (FISH) study of a patient with Wolf-Hirschhorn syndrome. FISH photograph shows deletion of a locus-specific probe for the Wolf-Hirschhorn critical region (absence of a probe signal at 4p16.3).
G-banded karyotype showing deletion of 4p, derived from the mother, with balanced translocation (4p;8p).
A girl with Wolf-Hirshhorn syndrome showing characteristic features of the condition.
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