Hypercholesterolemia in children with Smith-Magenis syndrome: del (17) (p11.2p11.2).
OBJECTIVE
Smith-Magenis syndrome (SMS), a probable contiguous gene syndrome due to an interstitial deletion of chromosome 17 band p11.2, is associated with a distinct and complex phenotype, including physical, developmental, and neurobehavioral features. The majority of SMS patients are deleted for a common approximately 4 Mb interval that includes the gene SREBF1, a transmembrane transcription factor that regulates the low density lipoprotein (LDL) receptor and plays a crucial role in cholesterol homeostasis. A systematic study of fasting lipid profiles of patients with SMS was conducted to determine the frequency of cholesterol abnormalities.


METHODS
Fasting lipid profiles were examined in 49 children (27F/22M) between the ages of 0.6 years to 17.6 years (mean, 6.9 years) with a cytogenetically confirmed diagnosis of SMS. Observed values for serum total cholesterol (TC), triglycerides (TG), LDL cholesterol, and high density lipoprotein cholesterol were compared with published norms. The body mass index (BMI) was used as a measure of nutritional status.


RESULTS
Mean TC was significantly higher than published NHANES III pediatric norms (P < 0.0008). Overall 28 of 49 (57%) SMS subjects had lipid values greater than the 95th percentile for age and gender for at least one or more of the following: TC, TG, and/or LDL. Only 16 SMS subjects (32%) were within normal limits for all three of these variables. BMI values showed minimal positive correlation to SMS lipid values; however, no consistent effect was found. Thus BMI values alone do not explain the marked trend in increased TC, TG, and/or LDL observed in the SMS group. Based on the American Academy of Pediatrics recommended lipid levels for children and adolescents, only one third of SMS subjects fall within normal range for TC and LDL; an additional one third each measure "borderline" or "high" for these values.


CONCLUSIONS
Hypercholesterolemia is common in SMS and may serve as a useful early clinical biochemical marker of the syndrome.
Medical Genetics Branch, National Human Genome Research Institute, NIH, Bldg. 10, Room 10C103, 10 Center Drive, MSC 1875, Bethesda, MD 20892-1875, USA.
Ann C M
AC
Smith
Andrea L
AL
Gropman
Joan E
JE
Bailey-Wilson
Ozlem
O
Goker-Alpan
Sarah H
SH
Elsea
Jan
J
Blancato
James R
JR
Lupski
Lorraine
L
Potocki
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D015992:Body Mass Index; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002886:Chromosomes, Human, Pair 17; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D007223:Infant; D008297:Male; D051780:Sterol Regulatory Element Binding Protein 1; D013577:Syndrome; D014157:Transcription Factors; D014280:Triglycerides / Q000097:blood
D022762:CCAAT-Enhancer-Binding Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004268:DNA-Binding Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol