PMC6491806_01
(A) Pedigree of the family segregating severe MTHFR deficiency. Pedigree clearly depicts an autosomal recessive mode of inheritance. Circles and squares represent females and males, respectively. Clear symbols represent normal, while filled symbols represent affected individuals. Slashes represents deceased individuals and triangle represents spontaneous abortion (SAB). The individual numbers labeled with asterisks were subjected to WES and the red arrow indicates the proband. (B) Pictures of the affected individual exhibiting microcephalic features at 1 month of age. (C) Brain MRI showing axial, coronal, and both T2 weighted images. These images revealed bilateral abnormal and symmetrical high signal intensity along the bilateral frontal horn in white matter, and the superior part of the periventricular deep white matter as well as within the subcortical basal temporal lobe white matter. The images also showed severely dilated ventricles and loss of white matter in cerebral hemispheres with prominent extra-axial CSF spaces. (D) A recent photograph of the proband (III-7) showing severe MTHFR deficiency.
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PMC6491806_02_fneur-10-00411-g0001.jpg
F1
During the first clinical investigation, the proband (female; III-7) was 1-month-old with features such as non-obstructive hydrocephalus, recurrent apnea, microcephaly, and white matter abnormality (Figure 1B). At birth, the head circumference was 31.5 cm, and the birth weight was 2,980 grams (Figure 1B). High signal intensity was observed in the white matter along the bilateral horn deep in the white matter, suggestive of white matter disease (Figure 1C). Follow-up examination after 10 months revealed that the proband could support her head but could not sit without support and may easily roll over (Figure 1D).
PMC6491806_02
(A) Pedigree of the family segregating severe MTHFR deficiency. Pedigree clearly depicts an autosomal recessive mode of inheritance. Circles and squares represent females and males, respectively. Clear symbols represent normal, while filled symbols represent affected individuals. Slashes represents deceased individuals and triangle represents spontaneous abortion (SAB). The individual numbers labeled with asterisks were subjected to WES and the red arrow indicates the proband. (B) Pictures of the affected individual exhibiting microcephalic features at 1 month of age. (C) Brain MRI showing axial, coronal, and both T2 weighted images. These images revealed bilateral abnormal and symmetrical high signal intensity along the bilateral frontal horn in white matter, and the superior part of the periventricular deep white matter as well as within the subcortical basal temporal lobe white matter. The images also showed severely dilated ventricles and loss of white matter in cerebral hemispheres with prominent extra-axial CSF spaces. (D) A recent photograph of the proband (III-7) showing severe MTHFR deficiency.
fneur-10-00411-g0001.jpg
PMC6491806_02_fneur-10-00411-g0001.jpg
F1
During the first clinical investigation, the proband (female; III-7) was 1-month-old with features such as non-obstructive hydrocephalus, recurrent apnea, microcephaly, and white matter abnormality (Figure 1B). At birth, the head circumference was 31.5 cm, and the birth weight was 2,980 grams (Figure 1B). High signal intensity was observed in the white matter along the bilateral horn deep in the white matter, suggestive of white matter disease (Figure 1C). Follow-up examination after 10 months revealed that the proband could support her head but could not sit without support and may easily roll over (Figure 1D).