Fetal intracranial calcification: Pseudo‐TORCH phenotype and discussion of related phenotypes

Abstract

Fetal intracranial calcification (ICC) noted during antenatal imaging poses a diagnostic challenge. Although this presentation is most commonly associated with intrauterine infection, non-infectious causes of fetal ICC have been reported and include metabolic, genetic, or hemodynamic conditions. We report on a patient with antenatally detected extensive ICC, in whom postnatal imaging revealed a distinctive band-like ICC with abnormal gyral pattern and a negative serology for TORCH infections. Such a constellation of findings have been previously described under the terminology of "pseudo-TORCH phenotype," and we posit that our patient represents this entity. Our patient had unreported dysmorphic features, which expands the phenotypic spectrum of this recently described heterogenous condition. In addition we report on the progression of the phenotype both clinically and radiologically. In view of the limited information available for the differential diagnosis of fetal ICC, we also review the available literature on this topic.

Zika Virus–Associated Micrencephaly: A Thorough Description of Neuropathologic Findings in the Fetal Central Nervous System

“…23,24 Importantly, our neuropathologic evaluation demonstrated that the Zika virus-infected fetal brain shares most of the neuroimaging changes seen in other intrauterine TORCH infections and even in pseudo-TORCH phenotypes. 6,7,8,25,26 It is difficult to make a comparison with the neuropathology of such cases because relatively few autopsies with brain examinations have been performed, 27 not only in cases of Zika virus-associated microcephaly but also in other intrauterine fetal brain infections. 28,29 Some changes, especially those of a malformed cortex, have frequently been described as polymicrogyria on MRI, which should be interpreted with caution.…”

“…6 Some cases with fetal, intracranial, bandlike calcifications, similar to those produced by TORCH agents but without confirmed intrauterine viral infection, have been described under the term pseudo-TORCH. 7,8 The most-frequent microorganisms affecting the fetal brain and causing microcephaly, usually accompanied by calcifications, are cytomegalovirus and Toxoplasma gondii. 6 An outbreak of microcephaly in Brazil, causally associated with the Zika virus epidemic since May 2015, has resulted in this emerging viral infection becoming the leading causative agent of microcephaly in South and Central America 9,10 and a serious threat to pregnant women from other countries who have visited that region.…”

Pseudo Toxoplasmosis

“…Narrowly-defined pseudo-TORCH syndrome (al-Dabbous et al, 1998;Baraitser et al, 1983;Briggs et al, 2008;Burn et al, 1986;Cohen et al, 2012;Ishitsu et al, 1985;Knoblauch et al, 2003;Kulkarni et al, 2010;Nakamura et al, 2011;Reardon et al, 1994;Vivarelli et al, 2001;Watts et al, 2008;Wieczorek et al 1995), also called Baraitser-Reardon syndrome (Vivarelli et al, 2001), or band-like calcification with simplified gyration and polymicrogyria (BLCPMG; MIM: 251290) (Abdel-Salam & Zaki, 2009;Briggs et al, 2008;O'Driscoll et al, 2010), is associated with microcephaly and intracranial calcifications mimicking congenital toxoplasmosis in the absence of infection. Ocular changes are not reported with pseudo-TORCH syndrome / AGS.…”

“…When congenital toxoplasmosis is excluded, these case are diagnosed as having pseudo toxoplasmosis (Hervouet, 1961), pseudo-TORCH (toxoplasma, rubella, cytomegalovirus, and herpes simplex) syndrome (Baraitser et al, 1983;Burn et al, 1986;Cohen et al, 2012;Ishitsu et al, 1985;Knoblauch et al, 2003;Kulkarni et al, 2010;Nakamura et al, 2011;Reardon et al, 1994;Vivarelli et al, 2001;Watts et al, 2008;Wieczorek et al, 1995) or congenital infection-like syndrome (Abdel-Salam & Zaki, 2009;al-Dabbous et al, 1998;al-Gazali et al, 1999;Dale et al, 2000;Knoblauch et al, 2003;Kulkarni et al, 2010;Mishra et al, 2002;Mizuno et al, 2011;Slee et al,1999).…”

“…These signs include microcephaly (Aalfs et al, 1995;Abdel-Salam & Zaki, 2009;AbdelSalam et al, 1999;Abdel-Salam et al, 2000;Ahmadi & Bradfield, 2007;Aicardi & Goutières, 1984;al-Dabbous et al, 1998;al-Gazali et al, 1999;Alzial et al, 1980;Angle et al, 1994;Atchaneeyasakul et al, 1998;Baraitser et al, 1983;Bogdan, 1951;Book et al, 1953;Briggs et al, 2008;Burn et al, 1986;Cantú et al, 1977;Casteels et al, 2001;Dale et al, 2000;EventovFriedman et al, 2009;Feingold & Bartoshesky 1992;Fisch et al, 1973;Fryns et al, 1995;Hoyeraal et al, 1970;Hordijk et al, 1996;Hreidarsson et al, 1988;Ishitsu et al, 1985;Jarmas et al, 1981;Kloepfer et al, 1964;Knoblauch et al, 2003;Komai et al, 1955;Kozma et al, 1996;Kulkarni et al, 2010;Leung, 1985;Limwongse et al, 1999;McKusick et al, 1966;Mishra et al, 2002;Nakamura et al, 2011;Nemos et al, 2009;Ostergaard et al, 2012;Pearson et al, 2008;Reardon et al, 1994;…”