96 Smith-Lemli-Opitz Syndrome
SLOS
Microcephaly, ptosis, anteverted nares, long philtrum, hypospadias/cryptorchidism, mental retardation
Frequency: 1 in 40,000 births; over 350 patients re- ported.
Genetics
Autosomal recessive (OMIM 270400); evidence for mutations in the sterol delta-7 reductase gene, which maps to 11q12-q13.
Clinical Features
• Growth retardation, oligohydramnios, prematuri- ty
• Microcephaly (95%), bitemporal narrowing
• Ptosis (85%), epicanthal folds (40%), strabismus (40%), cataract (10%)
• Short nose, broad nasal tip, anteverted nostrils (75%), long philtrum
• Small tongue, broad alveolar ridges (60%), rugous palate, cleft palate (50%)
• Micrognathia (80%)
• Low-set ears, abnormal pinnae (60%)
• Short neck with redundant skin folds
• Hypospadias (50%), cryptorchidism (59%), sex reversal, male pseudohermaphroditism, renal ab- normalities (renal duplication, hypoplastic kid- ney, hydronephrosis, cysts)
• Congenital heart defect (VSD,ASD, PDA, tetralogy of Fallot, AV canal, aberrant pulmonary veins), pancreatic anomalies, pyloric stenosis, lung seg- mentation defects
• Syndactyly of 2nd and 3rd toes (80%); short, clin- odactylous 5th toe; index finger may overlap mid- dle finger; short thumb (nearly all cases); postaxi- al polydactyly of hands or feet; clubfoot
• Mental retardation, hypotonia (50%), CNS defects (hydrocephalus, seizures, partial agenesis of cere- bellum and/or corpus callosum, hypoplasia of frontal lobes, reduced myelination, holoprosen- cephaly)
• Defect in cholesterol metabolism, with deficiency in 7-dehydrocholesterol reductase, low maternal estriol in pregnancy
Differential Diagnosis
• Meckel syndrome
• Desmosterolosis (another defect in cholesterol metabolism)
Radiographic Features Skull
• Microcephaly, abnormal skull shape including scaphocephaly
• Micrognathia Hands and Feet
• Soft-tissue syndactyly of 2nd and 3rd toes
• Postaxial (rarely preaxial) polydactyly of hands and feet
• Brachydactyly
• Camptodactyly
• Hypoplastic thumb, proximally placed thumb
• Clubfoot (metatarsus adductus, pes equinovarus, metatarsus varus)
Joints
• Hip dislocation (50%)
Generalized Skeletal Abnormalities
• Stippled epiphyses
Bibliography
Johnson VP. Smith-Lemli-Opitz syndrome: review and report of two affected siblings. Z Kinderheilkd 1975; 119: 221–34 Kelley RI. RSH/Smith-Lemli-Opitz syndrome: mutations and
metabolic morphogenesis. Am J Hum Genet 1998; 63:
322–6
Neklason DW, Andrews KM, Kelley RI, Metherall JE. Biochem- ical variants of Smith-Lemli-Opitz syndrome. Am J Med Genet 1999; 85: 517–23
Opitz JM, Penchaszadeh VB, Holt MC, Spano LM. Smith-Lem- li-Opitz (RSH) syndrome bibliography. Am J Med Genet 1987; 28: 745–50
Ryan AK, Bartlett K, Clayton P, Eaton S, Mills L, Donnai D,Win- ter RM, Burn J. Smith-Lemli-Opitz syndrome: a variable clinical and biochemical phenotype. J Med Genet 1998; 35:
558–65
Tint GS, Irons M, Elias ER, Batta AK, Frieden R, Chen TS, Salen G. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med 1994; 330:
107–13
Wassif CA, Maslen C, Kachilele-Linjewile S, Lin D, Linck LM, Connor WE, Steiner RD, Porter FD. Mutations in the human sterol delta7-reductase gene at 11q12–13 cause Smith-Lem- li-Opitz syndrome. Am J Hum Genet 1998; 63: 55–62
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Smith-Lemli-Opitz Syndrome 874
Fig. 96.1 a, b. Patient 1, age 1 year. a Ptosis, epicanthus, strabis- mus, short nose, anteverted nostrils, long philtrum, micro- gnathia, and b severe brachydactyly
a
b
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Fig. 96.2. a, bPatient 2, newborn; c, d patient 3, age 3 years. Abnormally small overall skull with increased anteroposterior diameter in both patients. Note bitemporal narrowing and micrognathia (a, b) and obtuse mandibular angle (d)
a b
c d
Smith-Lemli-Opitz Syndrome 876
Fig. 96.3 a, b. Patient 2, newborn.
Bell-shaped thorax, and 11 pairs of thin ribs. Vertebrae appear nor- mal
a b
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Fig. 96.5. a, bPatient 2, newborn. Note postaxial hexadactyly (a), bilateral thumb hypoplasia, hypoplastic/aplastic middle phalanges, and finger camptodactyly. c Patient 3, age 3 years.
Brachydactyly, hypoplasia of middle phalanges, clinodactyly of fingers 2 and 5, and proximally positioned thumb
a b c
