Congenital Malformations and Chromosomal Aberrations

Abstract

Among a great number of chromosomal aberrations, the absence of cerebral malformations does not explain the reason for mental retardation and will lead to interpreting as normal the echography of a fetus which, after birth, will be revealed to have a trisomy. Trisomic brain anomalies are not constant or obligatory, but some of them (holoprosencephaly for 61 % of trisomy-13 and agenesis of corpus callosum for 8% of trisomy-18) have a degree of specificity. As for cerebral and cerebellar heterotopias, they cannot be considered as real malformations as they are frequently found in premature newborns and disappear with maturation, thus proving that they are a sign of immaturity. There is still a lot of work to be done before we are able to meet the request for fetal integrity formulated by contemporary couples.

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

“…In this study, karyotyping analysis revealed 2 cases of aneuploidy (one is trisomy 21 and another is trisomy 13) with 10.53% of detection rate, which was basically consistent with the previous report 12 . Up to now, 35 (35/172) patients with trisomy 13 have been reported to be associated with CCA 12–18 . Only 20 cases of trisomy 21 have been reported either in detailed or partial case reports, suggesting rare association of trisomy 21 with CCA.…”

“… 12 Up to now, 35 (35/172) patients with trisomy 13 have been reported to be associated with CCA. 12 , 13 , 14 , 15 , 16 , 17 , 18 Only 20 cases of trisomy 21 have been reported either in detailed or partial case reports, suggesting rare association of trisomy 21 with CCA. Jacob et al 19 presented the first report of a monozygotic twin pregnancy with trisomy 21 and partial ACC in both fetuses.…”

Cerebellar heterotopia in an 11‐year‐old child with KDM6B‐related neurodevelopmental disorder: A case report and review of the literature

“…Cerebellar heterotopia, categorized by Patel and Barkovich among isolated cerebellar hemispheric dysplasia (Patel & Barkovich, 2002), are nodules of neurons abnormally located in the cerebellar white matter due to an alteration in neuronal migration during cerebellar development (Laure‐Kamionowska & Maślińska, 2011; Sarnat, 2018). To date, cerebellar heterotopia has been reported as recurrent findings in CHARGE syndrome (Wright et al, 2019) and trisomy 21 (Battin, 1986; Laure‐Kamionowska & Maślińska, 2011), they have sometimes been described in trisomy 18 (Battin, 1986) and rarely associated, almost always in single patients, to other genetic conditions such as Turner syndrome (Laure‐Kamionowska & Maślińska, 2011), ornithine carbamoyl transferase deficiency (Harding et al, 1984), MKS3‐related Meckel syndrome (Adams et al, 2012), occipital horn syndrome (Palmer & Percy, 2001), OPHN1‐related syndrome (Rocas et al, 2013), PAK1‐related syndrome (Scorrano et al, 2023) and clinically diagnosed Fryns syndrome (Clark & Fenner‐Gonzales, 1989; Slavotinek, 2004). Of note, KDM6B is highly expressed in cerebellar neurons, where it plays an important role in the main genetic pathways involved in mechanisms of cerebellar neurons migration during development such as SDF‐1/CXCR4 (Huang et al, 2014), BDNF/TrkB (Borghesani et al, 2002) and SHH signaling (Lewis et al, 2004; Liu et al, 2022; Shi et al, 2014), as well as in non‐neuronal cells such as Bergmann glia (Wijayatunge et al, 2018), which constitutes the scaffold for neuronal migration (Buffo & Rossi, 2013).…”

Down syndrome and fetal ventriculomegaly

“…Three of their seven cases of mild ventriculomegaly had trisomy 21. Intriguingly, ventriculomegaly is not commonly described in children with trisomy 21 (Vinken ef al., 1977;Battin, 1986;Gullotta et al, 1981). The clinical sigdicance of a high incidence of mild fetal ventriculomegaly in fetuses with trisomy 21 remains to be elucidated.…”