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At a glance

A lethal form of mesomelic dwarfism associated with severe multiple cardiac, respiratory, and skeletal malformations. It is also known as the polydactyly, sex reversal, renal hypoplasia, and unilobular lung disease.

Synonyms

Smith-Lemli-Opitz Syndrome Type II; Lethal Acro-Dysgenital Syndrome; Lethal Multiple Congenital Anomaly Syndrome.

History

First described by J. C. Rutledge in 1984.

Genetic inheritance

Autosomal recessive; allelic to Smith-Lemli-Opitz Syndrome Type I.

Pathophysiology

Results from a mutation in either the DHCR7 (7-dehydrocholesterol-delta7-reductase) gene on 11q12-13. The classic paradigm is an inborn error of metabolism, which includes the accumulation of a toxic precursor (7DHC) leading to the deficiency in production of an essential product (cholesterol). The absence in cholesterol can be implicated in the production of all the anomalies described (polymalformative syndrome) and results in intrauterine growth retardation. Cholesterol is required for normal development because of its involvement in cell and mitochondrial membranes, as well as steroid metabolism and myelination.

Diagnosis

Clinical features (mesomelic dwarfism, micrognathia, V-shaped upper lip, ambiguous genitalia, clubfeet, fused fontanelles, inclusion cysts of the tongue, widely spaced nipples, and digital anomalies). Prenatal diagnosis by ultrasonography and analysis of cholesterol level from amniocentesis is possible.

Clinical aspects

Features include mesomelic dwarfism, craniofacial deformations (fused fontanelles, low-set ears, micrognathia, V-shaped upper lip, thick alveolar ridges, high-arched palate or cleft palate, abnormal tongue, cataract), cardiac and respiratory malformations (severe congenital heart defect, pulmonary hypoplasia, unilobar lungs, laryngeal hypoplasia), genitourinary signs (ambiguous genitalia, oligopapillary, renal hypoplasia), gastrointestinal (gallbladder hypoplasia, pancreatic islet cell hyperplasia, megacolon), and orthopedic malformations (polydactyly, syndactyly, clubfoot, joint contractures). Cerebellar hypoplasia is associated. Affected patients usually die within a few hours or days of birth.

Precautions before anesthesia

Complete examination and full assessment of cardiac, respiratory, and renal function (clinical, radiographs, echography, arterial blood gas analysis). Complete biochemistry evaluation should be obtained. Volemia should be assessed because of renal anomalies. Because of the possibility of laryngeal hypoplasia, proper evaluation must be sought.

Anesthetic considerations

No reported experience because of the rarity and very early lethality of the syndrome. Direct laryngoscopy and tracheal intubation are likely to be difficult because of facial anomalies. Postoperative ventilatory support may be necessary.

Pharmacological implications

Perioperative fluid regimen and drugs doses should be adapted to renal function. Cardiac prophylactic antibiotics as indicated.

References

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Curry  CJR, Carey  JC, Holland  JS,  et al: Smith-Lemli-Opitz syndrome type II: Multiple congenital anomalies with male pseudohermaphroditism and frequent early lethality. Am J Med Genet 26:45, 1987.  [PubMed: 3812577]
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Donoghue  SE, Pitt  JJ, Boneh  A, White  SM: Smith-Lemli-Opitz syndrome: Clinical and biochemical correlates. J Pediatr ...

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