Diaphragmatic Defects, Limb Deficiencies, And Ossification Defects Of Skull

Clinical Features

Froster et al. (1996) described a 'possibly new' autosomal recessive syndrome in 4 successive fetuses (2 females; 2 males) from a healthy nonconsanguineous couple. Both prenatal and postnatal findings were reported. The spectrum of malformations included diaphragmatic defects, hypoplastic lungs, omphalocele, limb deficiencies, syndactyly of toes, and ossification defect of the skull. The specific spectrum of anomalies was not fully compatible with that of any established syndrome. No prenatal exposure to any possible teratogen was found. The limb anomalies were more severe in the 2 last born fetuses. The diaphragmatic defect, which was of postural lateral Bochdalek type, was found in all 4. Gonadal mosaicism in 1 parent was mentioned as a possible alternative to autosomal recessive inheritance.

Koifman et al. (2009) reported a female fetus diagnosed prenatally with left diaphragmatic hernia and absence of the right femur. Family history was unremarkable and the parents were not related. The pregnancy was terminated, and on autopsy the fetus was found to have complete absence of the right femur and a left diaphragmatic hernia. The only other abnormality observed was bilateral fifth finger clinodactyly. The authors proposed that the infant had the same condition as the sibs reported by Froster et al. (1996) and suggested that the condition be called Froster syndrome.

Gardham et al. (2013) reported 2 sibs, born to healthy nonconsanguineous parents, with features similar to those in the patients reported by Froster et al. (1996) and Koifman et al. (2009). The first, a male fetus, was found on prenatal ultrasonography to have multiple congenital anomalies. Pathologic examination following pregnancy termination showed bilateral diaphragmatic hernia, limb hypoplasia, omphalocele, partial intestinal malrotation, absent right pelvic bone with a single long bone in the right leg, and right testicular atrophy. In addition, the fetus had mild hypertelorism, low-set ears, and an upturned nose. The second sib, a female fetus, was also found on prenatal ultrasonography to have a diaphragmatic hernia. Following pregnancy termination, pathologic examination showed bilateral diaphragmatic hernia with lung hypoplasia. No other abnormalities were observed. A maternally inherited 1.2-Mb duplication in chromosome 8p22 was seen in the female sib on oligonucleotide microarray, but was believed to be a benign copy number variant.