Prenatal identification of a pathogenic maternal FGFR1 variant in two consecutive pregnancies with fetal forebrain malformations

Figures & data

Table 1a. Clinical data of the second (I) and third (II) pregnancies of the proposita, both of which were terminated due to adverse fetal outcomes.

Case	Parental details			Gestation at diagnosis	Phenotypes (HPO terms)	Obstetric history	Family history	Outcome
I	Maternal	Age	33	Pregnancy previously terminated at 21w0d	Unilateral cleft lip-palate, absent septum pellucidum, intrauterine growth restriction.	Gravida 2, para 1.	Unremarkable	Pregnancy termination
		Medical history	Unremarkable
	Paternal	Age	37
		Medical history	Unremarkable
II	Maternal	Age	34	19w0d	Hypoplasia of the corpus callosum, absent cavum septum pellucidum, lobar holoprosencephaly.	Gravida 3, para 1.	Unremarkable	Pregnancy termination
		Medical history	Unremarkable
	Paternal	Age	38
		Medical history	Unremarkable

Figure 1. Fetal neuroimaging findings. Ultrasound (a) and magnetic resonance imaging (b) of the sagittal view showing the hypoplasia of the corpus callosum (white arrows). Magnetic resonance imaging of the transverse (c) and coronal (d) view showing partial separation of the frontal lobe (white asterisk), incomplete development of the corpus callosum and the presence of the sagittal scissure (white arrowhead), suggestive of lobar holoprosencephaly.

Table 1b. Genetic findings on amniotic fluid sampling in both pregnancies of the proposita.

Case	Procedure (gest. age)	Sample	Performed test	Result	Variant	ACMG classification	Inheritance and zygosity	Interpretation
I	Amniocentesis (20w0d)	Cultured amniocytes	Karyotype	46,XX	–	–	–	–
	Amniocentesis (as above)	Cultured amniocytes	CMA	arr(X-22)x2	–	–	–	–
	Amniocentesis (as above)	Cultured amniocytes and parentals’ lymphocytes	Trio exome sequencing	FGFR1 (ENST00000447712.7)	NM_023110.3: c.296A>G p.(Tyr99Cys)	Pathogenic	Maternal, heterozygous	Causative of fetal phenotype
II	Amniocentesis (16w0d)	Cultured amniocytes	Karyotype	46,XX	–	–	–	–
	Amniocentesis (as above)	Cultured amniocytes	FGFR1 exon 3 Sanger sequencing	FGFR1 (ENST00000447712.7)	NM_023110.3: c.296A>G p.(Tyr99Cys)	Pathogenic	Maternal, heterozygous	Causative of fetal phenotype

Abbreviations: CMA, chromosomal microarray; HPO, Ontology of Human Phenotype; ACMG, American College of Medical Genetics [11].

Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369(9569):1287–1301. doi: 10.1016/S0140-6736(07)60601-1.

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Data availability statement

The datasets supporting the conclusions of this article are included within the article (and its additional files).