Lethal osteosclerotic bone dysplasia is a rare disorder characterized by generalized osteosclerosis with periosteal new bone formation and distinctive facies. The facial appearance in lethal osteosclerotic bone dysplasia (Raine syndrome) is characterized by a wide anterior fontanelle, exophthalmos and severe depression of the nasal bridge with severe midface hypoplasia. The nose in many cases appears severely hypoplastic but this is not consistent. The mouth is usually triangular. Other abnormalities include gum hypertrophy, natal teeth and cleft palate/uvula.
The radiological findings in lethal osteosclerotic bone dysplasia include generalized osteosclerosis of all bones and the base of the skull with cortical hyperostosis and periosteal new bone formation. The ribs usually appear irregular in shape due tp fractures.
By year 2003, a total of nine cases were described in the world with lethal osteosclerotic bone dysplasia. Of these nine cases, five reported patients were Arabs from Saudi Arabia, Palestine, and Egypt indicating that the gene is probably more common in the region. Parental consanguinity in many of the cases strongly supports suggestions that this is an autosomal recessive disorder.
Al-Gazali et al. (2003) reported a male infant from unrelated Egyptian parents, residents of the United Arab Emirates, with Raine syndrome. There were no histories of any congenital anomaly or genetic disease or of maternal drug intake during pregnancy. Prenatal ultrasound showed polyhydramnios and short limbs. The baby presented at birth with severe craniofacial anomalies including a wide anterior fontanel, exophthalmos, severe depression of the nasal bridge with a hypoplastic midface, bilateral choanal atresia, and a large protruding tongue. All the limbs were short and the thorax was small with widely spaced nipples. Radiologically, there was increased bone density in some bones, periosteal new bone formation, and marked bowing of the femurs, tibias, and ulnas. Al-Gazali et al. (2003) suggested that osteosclerosis in Raine syndrome is not necessarily severe and generalized, and that bowing of the long bones is another variable radiologic feature of the syndrome. Subsequent molecular investigation demonstrated that this disease resulted in this case from a splice site c.915-3C>G mutation in the FAM20C gene (Simpson et al., 2007).
Shalev et al. (1999) described a newborn girl with a lethal sclerosing bone dysplasia leading to prenatal skeletal alterations and microcephaly, intracranial calcifications, and generalized osteosclerosis. Other findings included bilateral severe proptosis with optic atrophy, everted lower eyelids, severely hypoplastic nose with choanal atresia, depressed nasal bridge, and mid-face hypoplasia with small mandible giving rise to a fish-like facial appearance. Mouth was triangular with cleft palate and hypertrophied gums. The ears were low set and the chest was narrow and short. Chromosomes were normal. The baby died on day 27 due to severe respiratory distress. Shalev et al. (1999) suggested an autosomal recessive mode of inheritance for the disease because parents were consanguineous.
Patel et al. (1992) described a case of osteopetrosis presenting with rare features of dysmorphism with proptosis due to hypoplasia of the orbits and the temporal bone. The case also had calcifications in the periventricular regions, the falx cerebri and the corpora colliculi. In 1996, Al-Mane and colleagues described a second patient with Raine syndrome, with a third known to be affected, all from the same family. In 1998 Al Mane et al. reported a girl, the third child of a Saudi consanguineous couple, who was stillborn after 37 weeks of gestation with a pregnancy complicated by polyhydramnios. The skeleton showed general increase of bone density. In the skull, the cranial base and vault were sclerotic although overall ossification appeared delayed with wide sutures and large fontanelles. Cranial CT demonstrated microcrania, an occipital encephalocele, facial hypoplasia and proptosis. Histopathological examination of the cord and placenta was normal except for retroplacental clot.
[See: Egypt > Al-Gazali et al., 2003; Simpson et al., 2007].