Wolf-Hirschhorn Syndrome Workup

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

Genetic testing

Diagnosis of WHS is confirmed by the detection of a deletion in the WHSCR.

Chromosomal microarray

This leads to diagnosis in greater than 95% of probands.

Cytogenetic analysis (routine and high resolution) 

This detects 50-60% of WHS.

Fluorescence in situ hybridization (FISH)

FISH using a WHCR probe detects more than 95% of deletions in WHS. Molecular cytogenetic studies using FISH allow the diagnosis to be made in patients with very small deletions or cryptic translocations.

FISH uses genetic markers that have been precisely localized to the area of interest. The absence of signal from either the maternal or paternal allele for the marker indicates monosomy for that chromosomal region.

Commercially, D4S96 or D4Z1 chromosome band 4p16.3–specific probe (Wolf-Hirschhorn region, Vysis, Inc) is available for FISH study.

Immune workup

Patients should be assessed for common variable immunodeficiency, immunoglobulin A (IgA) and immunoglobulin G2 (IgG2) subclass deficiency, IgA deficiency, impaired polysaccharide responsiveness, and normal T-cell immunity.


Imaging Studies

Imaging studies in WHS include the following:

  • Radiography - May reveal delayed bone maturation, microcephaly, hypertelorism, micrognathia, anterior fusion of vertebrae, fused ribs, dislocated hips, proximal radioulnar synostosis, clubfeet, and split hand/foot abnormality
  • Echocardiography - Should be obtained in all patients to evaluate for heart defects
  • Renal ultrasonography - Used to detect renal anomalies
  • Magnetic resonance imaging (MRI) and computed tomography (CT) scanning - May reveal underlying brain pathology, including agenesis of the corpus callosum and ventriculomegaly

In a study of 10 prenatal cases of Wolf-Hirschhorn syndrome (WHS), Xing et al found that the most common prenatally detected ultrasonographic features of the condition were intrauterine growth retardation (97.7%) and typical facial appearance (82.9%). Other phenotypic characteristics found ultrasonographically included renal hypoplasia (36.2%), cardiac malformation (29.8%), cleft lip and palate (25.5%), cerebral abnormalities (25.5%), skeletal anomalies (21.3%), and increased nuchal translucency/nuchal fold thickness (19%). [25]


Other Tests

These include the following:

  • Electroencephalogram-video monitoring - To evaluate for atypical or subtle seizures in children (aged 1-6 years)
  • Swallowing study - For feeding difficulty
  • Comprehensive audiologic and otologic evaluation - To rule out possible hearing impairment
  • Ophthalmologic examination
  • Developmental testing and referral to early intervention and appropriate school placement
  • Specific growth charts - Should be used to monitor growth parameters in patients with WHS between birth and age 4 years [11]


Gastrostomy may be necessary in infancy to protect the airway of patients with major feeding difficulty.