Prenatal diagnosis of complex phenotype in a 13-week-old fetus with an interstitial multigene deletion 20q13.13.-q13.2 by chromosomal microarray

Eur J Med Genet. 2017 Nov;60(11):589-594. doi: 10.1016/j.ejmg.2017.08.010. Epub 2017 Aug 12.


We report the first trimester three-dimensional ultrasonographic findings in a 13-week-old fetus with complex phenotype and a de novo 4.7 Mb multigene deletion encompassing chromosome region 20q13.13-q13.2 detected by chromosomal microarray. Fetal sonography detected radial-ray anomalies in the form of bilateral absence of thumbs and the left club hand deformity. The presence of single atrioventricular canal instead of the atrial septal defect typical for Holt-Oram syndrome pointed us to rather suspect the SALL4 related diseases. Central nervous system anomaly in the form of enlarged lateral brain ventricles with choroid plexus shifted backwards was not previously reported as a part of SALL4 related disorders. The pregnancy was terminated at 14 + 3 weeks of pregnancy and the autopsy confirmed ultrasonographic findings. Deleted region included 38 genes, where only SALL4, ADNP and KCNB1 heterozygote pathogenic variants were described to be cause of syndromic forms. Radial ray anomalies are common part of clinical picture of SALL4 related disorders. Despite the lack of prenatally described cases, we hypothesized that maldevelopment of lateral brain ventriculomegaly could be very early sonographic sign of disturbed ADNP expression causing Helsmoortel-Van der Aa syndrome, but in some extent also of KCNB1 related early-onset epileptic encephalopathy. Furthermore, the possible dosage-dependent influence of recessive genes located in this region cannot be also excluded. The use of genome-wide technologies enables the detection of subtle chromosomal imbalances and more precise familial genetic counseling regarding actual and future pregnancies.

Keywords: ADNP; Chromosome 20 deletion; Microarray; Radial ray anomaly; SALL4; Ventriculomegaly.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / diagnostic imaging
  • Abnormalities, Multiple / genetics*
  • Adult
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 20 / genetics*
  • Diagnosis, Differential
  • Female
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / diagnostic imaging
  • Heart Defects, Congenital / genetics*
  • Heart Septal Defects, Atrial / diagnosis
  • Heart Septal Defects, Atrial / diagnostic imaging
  • Heart Septal Defects, Atrial / genetics*
  • Homeodomain Proteins / genetics
  • Humans
  • Lower Extremity Deformities, Congenital / diagnosis
  • Lower Extremity Deformities, Congenital / diagnostic imaging
  • Lower Extremity Deformities, Congenital / genetics*
  • Nerve Tissue Proteins / genetics
  • Phenotype*
  • Pregnancy
  • Shab Potassium Channels / genetics
  • Transcription Factors / genetics
  • Ultrasonography, Prenatal*
  • Upper Extremity Deformities, Congenital / diagnosis
  • Upper Extremity Deformities, Congenital / diagnostic imaging
  • Upper Extremity Deformities, Congenital / genetics*


  • ADNP protein, human
  • Homeodomain Proteins
  • KCNB1 protein, human
  • Nerve Tissue Proteins
  • SALL4 protein, human
  • Shab Potassium Channels
  • Transcription Factors

Supplementary concepts

  • Holt-Oram syndrome