Spondylocostal Dysostosis 3, Autosomal Recessive

A number sign (#) is used with this entry because of evidence that autosomal recessive spondylocostal dysostosis-3 (SCDO3) is caused by homozygous or compound heterozygous mutation in the LFNG gene (602576) on chromosome 7p22.

For a phenotypic description and a discussion of genetic heterogeneity of spondylocostal dysostosis, see 277300.

Clinical Features

Sparrow et al. (2006) reported a proband of Lebanese background who presented with extensive congenital vertebral anomalies; long, slender fingers; and camptodactyly of the left index finger. X-ray and magnetic resonance imaging (MRI) scans showed multiple vertebral ossification centers in the thoracic spine, which showed fitted angular shapes similar to those seen in the patient with spondylocostal dysostosis (SCDO2; see 608681) caused by mutation in the MESP2 gene (605195) (Whittock et al., 2004). Severe foreshortening of the spine was emphasized by comparison of the patient's arm span (186.5 cm) with adult height (155 cm; lower segment 92.5 cm). In contrast to SCDO2, vertebral anomalies were also present in the cervical and lumbar spine.

Otomo et al. (2019) described a 9-month-old Japanese boy with a spinal deformity. His height was approximately -2.5 SD. He had multiple vertebral anomalies from cervical to sacral vertebrae as well as defect and fusion of ribs. Radiographs showed normal pelvis and long tubular bones, but a 'pebble-beach' appearance of the vertebral bodies. Lateral view of the cervical spine showed kyphosis and a hypoplastic odontoid process.

Molecular Genetics

In a Lebanese patient with spondylocostal dysostosis in whom mutations in the DLL3 (602768) and MESP2 genes were excluded, Sparrow et al. (2006) screened for mutations in the LFNG gene based on the phenotype of the homologous mouse mutant and identified a homozygous missense mutation (F188L; 602576.0001). Both parents with normal spinal and hand anatomy were heterozygous for the mutant allele. Based on comparison with the Lfng-null mouse, Sparrow et al. (2006) suggested that the hand anomalies in the proband were not caused by the LFNG mutation but were a secondary consequence of the cervical segmentation phenotype through nerve entrapment.

In a 9-month-old Japanese boy with spondylocostal dysostosis, Otomo et al. (2019) found compound heterozygosity for a missense (D201N; 602576.0002) and a frameshift (602576.0003) mutation in the LFNG gene. Each parent was heterozygous for 1 of the mutations. Neither mutation was found in the ExAC, ESP6500, or iJGVD databases.