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Articles » Aneuploidy » 4p-, Wolf-Hirschhorn syndrome

2007-10-06-04 Wolf-Hirshorn syndrome © Dudarewicz

Wolf-Hirshorn syndrome

Lech Dudarewicz, MD, PhD*; Lucjusz Jakubowski, MD, PhD*; Tatiana Chilarska, MD*; Nina Wieczorek-Cichecka, MD*; Wanda Hawula, MSc*; Magdalena Kozlowska, MSc*; Mariusz Grzesiak, MD**; Piotr Hincz, MD**.


Polish Mother’s Memorial Hospital, Department of Genetics, 281/289 Rzgowska St. 93-338 Lodz, Poland; Ph: 48 42 271 11 83;


Polish Mother’s Memorial Hospital, Department of Maternal-Fetal Medicine.


Wolf-Hirschhorn syndrome (WHS, MIM 194190) is caused by the loss of the genetic material of the distal part of the short arms of chromosome 4. It is a rare disorder, with the estimated frequency of 0.2:10,000 births. We present the case of the second trimester fetus diagnosed by amniocentesis, which was prompted by abnormalities detected on ultrasound.

Case report

A 27-years-old patient was screened at 13 weeks. The nuchal translucency was around the 90th centile. No other suspicious signs were noticed at that moment, although retrospectively micrognathia can be identified in the images obtained at that time. The next scan at 20th week revealed significant IUGR and a suspicion of ventricular septal defect, therefore the patient was offered genetic amniocentesis. Initially the patient refused invasive testing and looked for the second opinion scan elsewhere, which failed to confirm the findings. The next scan at our institution confirmed the findings and additionally the overriding aorta was noticed. The patient agreed to have the amniocentesis performed and as a result 4p deletion was noted on GTG banding [46,XX,del(4)(p15.2) karyotype], which is diagnostic of  the Wolf-Hirschhorn syndrome. The child was born by cesarean section at term in our institution and had typical health problems: low birth weight, major feeding difficulties etc. The child expired before cardiologic surgery, for which she had been scheduled for, was performed.

Images 1, 2: 13 weeks of gestation;  The image 1 shows the fetal profile; the image 2 shows the four chamber view of the heart with the ventricular septal defect. 


Images 3, 4: The images show overriding aorta and ventricular septal defect of the heart.


Images 5, 6: The images show overriding aorta and ventricular septal defect of the heart.


Images 7: 20th week of pregnancy. The image shows the facial profile of the fetus with micrognathia.

Video 1, 2: The videos show ventricular septal defect and the overriding aorta at the level of the four-chamber view of the heart.

 Images 8, 9: Postnatal appearance of the neonate.



Many prenatally diagnosed cases of Wolf-Hirschhorn syndrome have been described. Frequent abnormality on first trimester examination is increased nuchal translucency. Although nuchal edema is a very unspecific sign, with wide differential diagnosis, it warrants karyotyping, which leads straight to the diagnosis. Other frequently cited signs of  the Wolf-Hirschhorn syndrome are heart defects, characteristic facial dysmorphism (Greek helmet – like forehead and nose), ambiguous genitalia in boys (tulip sign) and constant and early IUGR. It is worth to point out, that the IUGR is early and can be demonstrated around mid-gestation. In our opinion detection of early IUGR should call for particular scrutiny of the fetal face, as in the favorable fetal position it should be possible to detect the facial dysmorphism characteristic of the Greek helmet and suspect the diagnosis before the karyotype is known. The differential diagnosis of the Greek helmet in the prenatal period encompasses other cases with IUGR, nuchal thickening, heart defects and micrognathia, so it is broad. Particularly trisomy 18 should be taken in consideration, the main differentiating feature being overlapping clenched fingers that are virtually a constant feature of trisomy 18 from 18 weeks of gestation on, and not typical of Wolf-Hirschhorn syndrome. Also a very rare Pitt-Roger-Danks syndrome, which is caused by a smaller size deletion 4p16.3 and as the consequence of the smaller amount of genetic material loss, presenting with only part of the Wolf-Hirschhorn syndrome spectrum, should be born in mind. Also 5p deletion and embryonic or fetal infections should be considered. The occurrence of the clinical features of the Wolf-Hirschhorn syndrome with normal classical karyotype should prompt search for the deletion of the Wolf-Hirschhorn syndrome critical region by molecular techniques (FISH, PCR).

The Wolf-Hirschhorn syndrome should be considered an indication for termination of pregnancy, if diagnosed before viability. After this time we feel, that the standard obstetrical care should not be altered. Search for associated anomalies should be performed and typical problems in the neonatal and later periods anticipated.
Recurrence risk is not increased, although gonadal mosaicism in the parents cannot be excluded. We propose detailed “genetic” sonogram with fetal cardiac scan at 12 and 19 weeks of the future pregnancies.


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