Wolf-Hirschhorn Syndrome Differential Diagnoses

Updated: Jan 19, 2021
  • Author: Santina A Zanelli, MD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Diagnostic Considerations

Pitt-Rogers-Danks syndrome (OMIM #262350) is now considered to be a part of WHS. 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 differential diagnosis includes 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

  • 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