Prenatal diagnosis of Fryns syndrome associated with a microdeletion at 8p23.1

Abstract

A 33-year-old, unmarried, primigravid woman was referred to the hospital at 24 weeks' gestation because of abnormal sonographic findings. The mother and the father were not consanguineous and healthy. There was no family history of congenital malformations. A cytogenetic study performed on the amniotic fluid cells revealed a karyotype of 46,XX at the 850band stage. Level II ultrasound at 24 weeks' gestation revealed polyhydramnios, macrocephaly with a head circumference of 24.1 cm (>95th centile), ventriculomegaly, increased nuchal thickness, micrognathia, a left congenital diaphragmatic hernia, a single umbilical artery, large for gestational age and left renal hypoplasia. Magnetic resonance imaging (MRI) showed cerebellar hypoplasia, left pulmonary hypoplasia, left diaphragmatic hernia and left renal hypoplasia (Figure 1(A) and (B)). A diagnosis of Fryns syndrome was made. The pregnancy was terminated at 25 weeks' gestation. A 1064-g female baby was delivered with a body length of 35 cm and a head circumference of 26.5 cm. The proband manifested characteristic dysmorphism of Fryns syndrome, including macrocephaly, brachytelephalangy, nail hypoplasia, a short webbed neck with redundant (a) (b) Figure 1-Prenatal magnetic resonance imaging (MRI) scans at 24 weeks' gestation show (A) left diaphragmatic hernia with intestines in the left hemithorax and left renal hypoplasia, and (B) cerebellar hypoplasia. RL: right lung, I: intestines, RK: right kidney, LK: left kidney

Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia

“…Chromosome 8p contains many copy number variant regions whose potential contribution to the development of birth defects has not been adequately studied. Recently, Chen et al 2007 described a patient with a Fryns‐like phenotype including CDH, macrocephaly, brachytelephalangy, nail hypoplasia, short webbed neck with redundant posterior nuchal skin, coarse face, flat and broad nasal bridge, hypertelorism, macrostomia, microretrognathia, and low‐set ears. The patient's phenotype was attributed to a de novo 0.7 Mb deletion within 8p23.1 [Chen et al, 2007].…”

“…Recently, Chen et al 2007 described a patient with a Fryns‐like phenotype including CDH, macrocephaly, brachytelephalangy, nail hypoplasia, short webbed neck with redundant posterior nuchal skin, coarse face, flat and broad nasal bridge, hypertelorism, macrostomia, microretrognathia, and low‐set ears. The patient's phenotype was attributed to a de novo 0.7 Mb deletion within 8p23.1 [Chen et al, 2007]. However, this deletion lies entirely within a known copy number variant region making it difficult to determine if this deletion is causal.…”

A Potential Relationship among Beta-Defensins Haplotype, SOX7 Duplication and Cardiac Defects

“…S. Giglio reported that haploinsufficiency of the region between WI-8372 (6.36–6.57 Mb) and D8S1825 (8.86–9.06 Mb) was associated with congenital heart defects using short-tandem repeat (STR) analysis [23], which suggested that the REPD may be related to CHD. However, Chen found that the microdeletion (chr8∶7227000–7916187) was insufficient to induce heart defects [24].…”

Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by genetics and protein interaction networks

“…More telomeric deletions, which do not overlap the hotspot region, may be unrelated to the “classical” del(8)(p23.1) syndrome. Chen et al [2007] reported an infant with CDH and additional anomalies, clinically diagnosed as having Fryns syndrome. Standard chromosome analysis was normal (46,XX) but focused aCGH revealed a de novo 0.7 Mb deletion in sub‐band 8p23.1, which extended from base pairs 7,227,000 to 7,916,187 (NCBI36/hg18).…”