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Smith-Lemli-Opitz syndrome

MIM.270400 11q12-q13

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Foot post-axial polydactyly and syndactyly 2-3 in Smith-Lemli-Opitz (...) Hand post-axial polydactyly in Smith-Lemli-Opitz syndrome Male pseudohermaphrodism and XY intersex in Smith-Lemli-Opitz (...)
SLOS, SLO syndrome, RSH syndrome, Rutledge lethal multiple congenital anomaly syndrome, polydactyly-sex reversal-renal hypoplasia syndrome, letahl acrodysgenital syndrome

Definition: Smith-Lemli-Opitz syndrome (SLO) is characterised by pre- and postnatal growth retardation and microcephaly, severe mental retardation, facial dysmorphic features, hypospadias and syndactyly between toes 2 and 3.

SLO results from cholesterol metabolic impairment with mutation of the 7-dehydro-cholesterol reductase gene (DHCR7, chromosome 11q12-q13).

SLOS patients have decreased cholesterol and increased 7-dehydrocholesterol (7-DHC) levels.

Dietary cholesterol supplementation improves systemic biochemical abnormalities; however, because of the blood-brain barrier, the central nervous system (CNS) is not treated. Simvastatin therapy has been proposed as a means to treat the CNS.

Synopsis

- systemic anomalies

- craniofacial anomalies

- cardiovascular anomalies (12797454)

- pulmonary anomalies

  • hypoplastic lungs
  • incomplete lobulation of the lungs

- gastrointestinal anomalies

- atypical mononuclear giant cells in pancreatic islets

- genital anomalies

- urinary anomalies

- limb anomalies

- cutaneous anomalies

  • severe photosensitivity
  • eczema
  • facial capillary hemangioma
  • blonde hair

- central nervous system

Biology

- low cholesterol
- elevated 7-dehydrocholesterol

Phenotypic variants

- lethal form of SLOS: Rutledge multiple congenital anomaly syndrome (RMCAS) (SLO2) (Ex-MIM.268670) (12717589)

Etiology

Smith-Lemli-Opitz syndrome is a autosomal recessive malformative syndrome caused by mutations in the sterol delta-7-reductase gene (DHCR7) (MIM.602858), which maps to 11q12-q13.

- mutations in the gene DHCR7 encoding sterol delta-7-reductase at 11q12-q13 (MIM.602858)

See also

- defect of cholesterol biosynthesis

Reviews

- Herman GE. Disorders of cholesterol biosynthesis : prototypic metabolic malformation syndromes. Hum Mol Genet. 2003 Apr 2 ;12(Suppl 1) :R75-88. PMID : 12668600

- Farese RV Jr, Herz J. Cholesterol metabolism and embryogenesis. Trends Genet. 1998 Mar ;14(3):115-20. PMID : 9540409

- Smith, D. W.; Lemli, L.; Opitz, J. M. : A newly recognized syndrome of multiple congenital anomalies. J. Pediat. 64: 210-217, 1964. PubMed ID : 14119520

References

- Digilio MC, Marino B, Giannotti A, Dallapiccola B, Opitz JM. Specific congenital heart defects in RSH/Smith-Lemli-Opitz syndrome: postulated involvement of the sonic hedgehog pathway in syndromes with postaxial polydactyly or heterotaxia. Birth Defects Res A Clin Mol Teratol. 2003 Mar;67(3):149-53. PMID: 12797454

- Singer LP, Marion RW, Li JK. Limb deficiency in an infant with Smith-Lemli-Opitz syndrome. Am J Med Genet. 1989 Mar;32(3):380-3. PMID: 2729358

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