Phenotypic spectrum of fetal Smith-Lemli-Opitz syndrome.
The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation syndrome caused by dehydrocholesterol reductase deficiency. The diagnosis is confirmed by high 7- and secondarily 8-dehydrocholesterol levels in plasma and tissues and/or by detection of biallelic mutations in the DHCR7 gene. The phenotypic spectrum of SLOS is broad, ranging from a mild phenotype combining subtle physical anomalies with behavioral and learning problems, to a perinatally lethal multiple malformations syndrome. The fetal phenotype of SLOS has been poorly described in the literature. We report a series of 10 fetuses with molecularly proven SLOS. Even in young fetuses, the facial dysmorphism appears characteristic. Genital abnormalities are rare in 46,XX subjects. Gonadal differentiation appears histologically normal and in agreement with the chromosomal sex, contrary to what has been previously stated. We observed some previously unreported anomalies: ulnar hypoplasia, vertebral segmentation anomalies, congenital pulmonary adenomatoid malformation, fused lungs, gastroschisis, holomyelia and hypothalamic hamartoma. This latter malformation proves that SLOS phenotypically overlaps with Pallister-Hall syndrome which remains clinically a major differential diagnosis of SLOS.
Clinical Genetics Unit, Rennes Sud University Hospital, Rennes, France. Chloe.QUELIN@chu-rennes.fr
Chloé
C
Quélin
Philippe
P
Loget
Alain
A
Verloes
Anne
A
Bazin
Bettina
B
Bessières
Annie
A
Laquerrière
Sophie
S
Patrier
Romulus
R
Grigorescu
Ferechté
F
Encha-Razavi
Sophie
S
Delahaye
Jean-Marie
JM
Jouannic
Bruno
B
Carbonne
Dominique
D
D'Hervé
Marie-Cécile
MC
Aubry
Guillaume
G
Macé
Thierry
T
Harvey
Yves
Y
Ville
Geraldine
G
Viot
Nicole
N
Joyé
Sylvie
S
Odent
Tania
T
Attié-Bitach
Claude
C
Wolf
Françoise
F
Chevy
Pascale
P
Benlian
Marie
M
Gonzales
D003937:Diagnosis, Differential; D005260:Female; D005333:Fetus / Q000473:pathology*; D006801:Humans; D008297:Male; D019370:Observation; D010641:Phenotype; D019082:Smith-Lemli-Opitz Syndrome / Q000473:pathology*