Fetal type IV glycogen storage disease: clinical, enzymatic, and genetic data of a pure muscular form with variable and early antenatal manifestations in the same family.

We report on a family of three consecutive fetuses affected by type IV glycogen storage disease (GSD IV). In all cases, cervical cystic hygroma was observed on the 12-week-ultrasound examination. During the second trimester, fetal hydrops developed in the first pregnancy whereas fetal akinesia appeared in the second pregnancy. The diagnosis was suggested by microscopic examination of fetal tissues showing characteristic inclusions exclusively in striated fibers, then confirmed by enzymatic studies on frozen muscle. Antenatal diagnosis was performed on the third and fourth pregnancies: cervical cystic hygroma and low glycogen branching enzyme (GBE) activity on chorionic villi sample (CVS) were detected in the third pregnancy whereas ultrasound findings were normal and GBE activity within normal range on CVS in the fourth pregnancy. Molecular analysis showed that the mother was heterozygous for a c.1471G > C mutation in exon 12, leading to the replacement of an alanine by a tyrosine at codon 491 (p.A491T); the father was heterozygous for a c.895G > T mutation in exon 7, leading to the creation of a stop codon at position 299 (p.G299X). GSD IV has to be considered in a context of cervical cystic hygroma with normal karyotype, particularly when second trimester hydrops or akinesia develop. Enzymatic analysis of GBE must be performed on CVS or amniotic cells to confirm the diagnosis. Characteristic intracellular inclusions are specific to the disease and should be recognized, even in macerated tissues after fetal death. Genetic analysis of the GBE gene may help to shed some light on the puzzling diversity of GSD IV phenotypes.

[Increased nuchal translucency pathophysiology]. / Physiopathologie de la nuque épaisse.

OBJECTIVES: Increased physiological nuchal translucency (NT) between 10 and 14 weeks of gestation is associated with chromosomal anomalies, mainly trisomy 21, developmental malformations and with normal fetus outcome. The aim of this study is to understand the cellular mechanisms leading to increased NT. MATERIALS AND METHODS: We examined five nuchal samples, a normal fetus from a fetal loss with a normal NT, a trisomy 21 fetus with an increased NT, two karyotypically normal fetuses with increased NT and a fetus with increased NT associated with an isolated cardiopathy. These morphological data were correlated with data from the literature. RESULTS: The pathological mechanism of increased NT is a posterior median mesenchymal edema of the fetal neck. It is associated with bilateral distension of jugular lymphatic vessels. CONCLUSION: Increased NT mechanisms are mainly related to a disturbance of embryonic lymphangiogenesis which might be a common denominator of the alteration of the composition of the extracellular matrix and of the cardiovascular and hemodynamic disorder. Nuchal morphological studies should be systematically performed to understand the mechanisms of increased NT.