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IEMbase 0192: DHCR7-related Smith-Lemli-Opitz syndrome

Scope

Field Value
IEMbase ID 192
Nosology 14.7.14.01
Gene DHCR7
External IDs OMIM:270400; ORPHA:818
Generated mapping MAPPED; Smith-Lemli-Opitz_syndrome.yaml
Candidate DisMech targets Smith-Lemli-Opitz_syndrome.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as DHCR7-related Smith-Lemli-Opitz syndrome, with alternate labels 7-dehydrocholesterol reductase deficiency, DHCR7 deficiency, and SLOS. Treatability is marked yes.

The biochemical rows include low-to-normal serum cholesterol and increased plasma 7-dehydrocholesterol and 8-dehydrocholesterol. Characteristic clinical rows include anteverted nares, axial hypotonia, broad alveolar ridges, epicanthal folds, excess digital whorls, growth retardation, microcephaly, micrognathia, and toe syndactyly affecting 2-3 or 2-5 toes. Additional rows include corpus callosum anomalies, ambiguous genitalia including 46,XY sex development findings, aggressive behavior, cataract, cerebellar hypoplasia, cleft palate, clubfoot, cryptorchidism, sensorineural deafness, dental spacing, developmental delay, feeding difficulty, hematuria, Hirschsprung disease, holoprosencephaly, hypodontia, hypospadias, intestinal dysmotility, irritability, liver dysfunction, photosensitivity, postaxial polydactyly, ptosis, pulmonary and renal anomalies, pyloric stenosis, rhizomelia, self-injury, strabismus, and supernumerary teeth. Treatment rows list simvastatin and cholesterol supplementation.

DisMech phenotype coverage

Smith-Lemli-Opitz_syndrome.yaml is the correct target. The local entry covers DHCR7 deficiency, reduced 7-dehydrocholesterol reductase activity, cholesterol deficiency, 7-dehydrocholesterol accumulation, oxysterol toxicity, impaired Smoothened/Hedgehog signaling, microcephaly, intellectual disability, prenatal and postnatal growth restriction, 2-3 toe syndactyly, cleft palate, postaxial polydactyly, male genital underdevelopment, serum 7-dehydrocholesterol, plasma cholesterol, DHCR7 genetics, dietary cholesterol, simvastatin, cholic acid, and avoidance guidance for 7-DHC-elevating exposures.

Concordance and completeness

Judgement: correct mapped target with high concordance.

IEMbase and DisMech agree on DHCR7/SLOS identity, the low cholesterol plus high 7-dehydrocholesterol biochemical signature, growth restriction, microcephaly, toe syndactyly, orofacial/genital/limb malformations, developmental delay, and cholesterol/simvastatin treatment context. IEMbase adds 8-dehydrocholesterol, broad alveolar ridges, excess digital whorls, dental spacing, hypodontia, supernumerary teeth, photosensitivity, Hirschsprung disease, pyloric stenosis, hematuria, and pulmonary/renal detail as possible enrichment targets. DisMech is stronger for mechanism, oxysterol toxicity, Smoothened/Hedgehog signaling, cholic acid, and medication/exposure avoidance.

Curation actions

  • Keep this record mapped to Smith-Lemli-Opitz_syndrome.yaml.
  • Consider 8-dehydrocholesterol, excess digital whorls, dental anomalies, photosensitivity, Hirschsprung disease, and pulmonary/renal rows as future enrichment targets.
  • Preserve local treatment nuance: IEMbase lists cholesterol and simvastatin, while DisMech also captures cholic acid and avoidance guidance.