Clinical characteristics: Spondylocostal dysostosis (SCDO), defined radiographically as multiple segmentation defects of the vertebrae in combination with abnormalities of the ribs, is characterized clinically by a short trunk in proportion to height; short neck; and non-progressive mild scoliosis in most affected individuals – rarely, more significant scoliosis occurs. Respiratory function in neonates with severe disease may be compromised by reduced size of the thorax. By age two years lung growth may improve sufficiently to support relatively normal growth and development. In severely affected individuals with restricted pulmonary capacity, there is a possibility that pulmonary hypertension may eventually impact cardiac function. Males with SCDO appear to be at increased risk for inguinal hernia.
Diagnosis/testing: The diagnosis of SCDO is based on radiographic features. Identification of biallelic pathogenic variants in DLL3, HES7, LFNG, MESP2, RIPPLY2, or TBX6 can confirm the diagnosis of autosomal recessive SCDO.
Management: Treatment of manifestations: Surgical intervention may be necessary when scoliosis is significant; external bracing (e.g., by use of a vertical expandable prosthetic titanium rib) may be considered, as well as growing rods and other devices as appropriate. Respiratory support, including intensive care, is provided as needed for the small proportion of individuals with acute respiratory distress and chronic respiratory failure. Expert management is indicated for chronic respiratory failure, which can result in pulmonary hypertension and cardiac failure. Standard treatment of neurologic problems associated with LFNG-related SCDO. Inguinal hernias are treated per routine.
Surveillance: Growth, spinal curvature, respiratory function, neurologic and motor function, and development should be monitored. The parents / care providers of young males need to be alert for the signs of inguinal hernia and its potential complications.
Genetic counseling: SCDO caused by biallelic pathogenic variants in DLL3, HES7, LFNG, MESP2, RIPPLY2, or TBX6 is inherited in an autosomal recessive manner. (Autosomal dominant inheritance of TBX6-related SCDO has been reported in a three-generation family.) If both parents are known to be heterozygous for an autosomal recessive SCDO-causing pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the autosomal recessive SCDO-related pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible. In experienced hands, detailed fetal ultrasound scanning is sensitive enough to detect multiple segmentation defects of the vertebrae as early as 13 weeks' gestation, especially when the malformation is anticipated and looked for specifically. However, molecular genetic testing of an at-risk pregnancy is considered the gold standard for accurate prenatal diagnosis.
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