Phenotypic and Neuropathological Characterization of Fetal Pyruvate Dehydrogenase Deficiency.

To distinguish pyruvate dehydrogenase deficiency (PDH) from other antenatal neurometabolic disorders thereby improving prenatal diagnosis, we describe imaging findings, clinical phenotype, and brain lesions in fetuses from 3 families with molecular characterization of this condition. Neuropathological analysis was performed in 4 autopsy cases from 3 unrelated families with subsequent biochemical and molecular confirmation of PDH complex deficiency. In 2 families there were mutations in the PDHA1 gene; in the third family there was a mutation in the PDHB gene. All fetuses displayed characteristic craniofacial dysmorphism of varying severity, absence of visceral lesions, and associated encephaloclastic and developmental supra- and infratentorial lesions. Neurodevelopmental abnormalities included microcephaly, migration abnormalities (pachygyria, polymicrogyria, periventricular nodular heterotopias), and cerebellar and brainstem hypoplasia with hypoplastic dentate nuclei and pyramidal tracts. Associated clastic lesions included asymmetric leukomalacia, reactive gliosis, large pseudocysts of germinolysis, and basal ganglia calcifications. The diagnosis of PDH deficiency should be suspected antenatally with the presence of clastic and neurodevelopmental lesions and a relatively characteristic craniofacial dysmorphism. Postmortem examination is essential for excluding other closely related entities, thereby allowing for biochemical and molecular confirmation.

Effect of the ellipsoid shape of the left ventricular outflow tract on the echocardiographic assessment of aortic valve area in aortic stenosis.

BACKGROUND: Previous studies showed discrepancies between echocardiographic and multidector row CT (MDCT) measurements of aortic valve area (AVA). OBJECTIVE: Our aim was to evaluate the effect of the ellipsoid shape of the left ventricular outflow tract (LVOT), as shown and measured by MDCT, on the assessment of AVA by transthoracic echocardiography (TTE) in patients with severe aortic stenosis. METHODS: This retrospective single-center study involved 49 patients with severe aortic stenosis referred before transcatheter aortic valve implantation. The AVA was deduced from the continuity equation on TTE and from planimetry on cardiac MDCT. Area of the LVOT was calculated as follows: on TTE, from the measurement of LVOT diameter on parasternal long-axis view; on MDCT, from manual planimetry by using multiplanar reconstruction perpendicular to LVOT. RESULTS: At baseline, correlation of TTE vs MDCT AVA measurements was moderate (R = 0.622; P < .001). TTE underestimated AVA compared with MDCT (0.66 ± 0.15 cm2 vs. 0.87 ± 0.15 cm2; P < .001). After correcting the continuity equation with the LVOT area as measured by MDCT, mean AVA drawn from TTE did not differ from MDCT (0.86 ± 0.2 cm2) and correlation between TTE and MDCT measurements increased (R = 0.704; P < .001). CONCLUSION: Assuming that LVOT area is circular with TTE results in constant underestimation of the AVA with the continuity equation compared with MDCT planimetry. The elliptical not circular shape of LVOT largely explains these discrepancies.

Foetal presentation of cartilage hair hypoplasia with extensive granulomatous inflammation.

Cartilage-hair-hypoplasia is a rare autosomal recessive metaphyseal dysplasia due to RMRP (the RNA component of the RNase MRP ribonuclease mitochondrial RNA processing complex) gene mutations. So far, about 100 mutations have been reported in the promoter and the transcribed regions. Clinical characteristics include short-limbed short stature, sparse hair and defective cell-mediated immunity. We report herein the antenatal presentation of a female foetus, in whom CHH was suspected from 23 weeks' gestation, leading to a medical termination of the pregnancy at 34 weeks gestation, and thereafter confirmed by morphological and molecular studies. Post-mortem examination confirmed short stature and limbs, and revealed thymic hypoplasia associated with severe CD4 T-cell immunodeficiency along with extensive non caseating epithelioid granulomas in almost all organs, which to our knowledge has been described only in five cases. Molecular studies evidenced on one allele the most frequently reported founder mutation NR_003051: g.70A>G, which is present in 92% of Finnish patients with Cartilage Hair Hypoplasia. On the second allele, a novel mutation consisting of a 10 nucleotide insertion at position -18 of the promoter region of the RMRP gene (M29916.1:g.726_727insCTCACTACTC) was detected. The founder mutation was inherited from the father, and the novel mutation from the mother. To our knowledge, this case report represents the first detailed foetal analysis described in the literature.