Diseases » Prader-Willi syndrome

Obesity

Obesity: Excerpt from The Diagnostic Approach to Symptoms and Signs in Pediatrics

Obesitycan be defined as an excess of body fat.

Children with obesity are at risk fordevelopment of diabetes mellitus, hypertension, sleep apnea, anddyslipidemia. They also may lack confidence and self-esteem andcan develop significant depression.

There are no agreed-on definitionsof obesity in children based on weight and height. Instead the term "overweight" isused when classifying children based on weight and height. Mostbut not all children who are significantly overweight are obese.

As surrogate measure of obesity, bodymass index (kg/m²) percentileor weight-for-height percentile can be used in clinical practice.The CDC (2001) developed a body mass index (kg/m²)for age percentiles in girls and boys 2–20 yrs, and weight-for-heightpercentiles for children <2 yrs. A body mass index or weight-for-height≥ ninety-fifth percentile for age and gender indicates obesity.

Principal Causes of Obesity

1. Geneticinfluences and environmental factors
2. Endocrine disorders
   1. Glucocorticoidexcess
   2. Hypothyroidism
   3. Growth hormone deficiency
   4. Hypothalamic dysfunction
   5. Polycystic ovary syndrome
3. Syndromes
   1. Alstrom syndrome
   2. Bardet-Biedl syndrome
   3. Carpenter syndrome
   4. Cohen syndrome
   5. Prader-Willi syndrome

Clinical Features and Diagnosis

Genetic Influences and Environmental Factors

In >99% ofobese children, the cause is a complex interaction between geneticinfluences and environmental factors leading to caloric intake inexcess of caloric expenditure. In general these children have normalphysical exam with normal intelligence, normal genital development,and normal or above average height for age. No further diagnosticinvestigation is necessary.

Whitaker et al. (1997) showed thatobesity in 1 or both parents can help predict a child'srisk of obesity in adulthood. In the past few years, 5 single-genedisorders resulting in early-onset obesity have been reported (Farooqiand O'Rahilly, 2000).

Endocrine Disorders

Endocrine causes of obesity are unusual exceptfor chronic corticosteroid therapy. Attenuation of growth velocityis characteristic of glucocorticoid excess, hypothyroidism, andgrowth hormone deficiency.

Glucocorticoid Excess

The term "Cushingsyndrome" is used to describe any type of glucocorticoidexcess. Most common cause of glucocorticoid excess in childhoodis chronic corticosteroid therapy. Other causes include adrenalhyperplasia and adrenal tumors (adenoma, carcinoma).

Cushing disease refers to pituitaryoverproduction of ACTH, which occurs with pituitary adenoma. EctopicACTH syndrome is production of excessive amount of ACTH from nonadrenalsource (neuroblastoma, Wilms tumor, thymoma, carcinoid).

Clinical features of glucocorticoidexcess include round facies, buffalo hump, hypertension, increasedweight gain, and decreased linear growth. Normally, serum cortisolconcentration tends to be higher in morning and lower in evening.Loss of this normal diurnal variation is screening test for Cushing syndrome.

Low-dose dexamethasone suppressiontest helps distinguish whether glucocorticoid excess is due to adrenalor pituitary cause. In low-dose test in normal individuals, plasmacortisol is decreased to <5 μg/dL. Individualswith Cushing disease usually fail to suppress cortisol with low-dosetest, but suppress with high-dose test. MRI should be performedwith suspected pituitary disease, although some tumors secretingACTH may be invisible with current techniques.

Failure to suppress cortisol secretionwith high-dose dexamethasone test usually indicates adrenal tumoror ectopic ACTH syndrome. Serum cortisol is high and ACTH is lowwith adrenal hyperplasia and adrenal tumors. ACTH stimulation testwith measurement of serum cortisol may help distinguish adrenaladenoma from adrenal carcinoma. Serum cortisol concentration usuallyincreases with adrenal adenoma, whereas no response occurs withadrenal carcinoma. With suspected adrenal tumor, CT of abdomen shouldbe performed. Both serum cortisol and ACTH concentrations are veryhigh with ectopic ACTH syndrome. Further investigation includingimaging is necessary to determine location and extent of tumor.

Hypothyroidism

Characteristic features of hypothyroidism,which may be congenital or acquired, are slow linear growth, dryhair and skin, constipation, cold intolerance, and sometimes enlargedthyroid gland. Thyroid hormone serum level [thyroxine (T₄)or free T₄] is low, whereas TSHlevel is high.

Growth Hormone Deficiency

Most striking feature of growth hormone deficiencyis severe decrease in postnatal linear growth (see Chap. 23, Growth Deficiency: Weight and Height).

Hypothalamic Dysfunction

Hypothalamiclesions associated with increased weight gain include neoplasm,trauma, and inflammatory disorders, but mechanism remains elusive.

Continuous food intake results in massiveweight gain.

CT and MRI help locate and define extentof lesion.

Polycystic Ovary Syndrome

Usuallyoccurs at puberty and is characterized by obesity, hirsutism, secondaryamenorrhea, and bilateral enlarged polycystic ovaries.

Ovaries may be palpable on exam andcan be demonstrated by pelvic U/S.

Hyperinsulinemia with insulin resistanceand acanthosis nigricans also may occur, especially in overweightindividuals. Measurement of fasting blood glucose and insulin levelsscreen for insulin resistance.

Cause of this disorder remains to bedetermined.

Syndromes

Alstrom Syndrome

This autosomal-recessive disorder, whosegene locus has been mapped to chromosome 2p13, is characterizedby obesity, usually occurring at 2–10 yrs, retinitis pigmentosawith visual loss, sensorineural hearing loss, acanthosis nigricans,chronic renal disease, diabetes mellitus with insulin resistance,and normal intelligence.

Bardet-Biedl Syndrome

Characterized by obesity, polydactyly, hypogonadism,pigmentary retinopathy with progressive decrease in visual acuity,and mental retardation. It has been linked to several genetic loci.

Carpenter Syndrome

Besides increased weight gain, characteristicfindings include flat nasal bridge, low-set ears, high-arched palate,lateral displacement of inner canthi, brachycephaly with craniosynostosis,polydactyly and partial syndactyly of feet, brachydactyly and partialsyndactyly of hands, and mental retardation.

Cohen Syndrome

In thisautosomal-recessive disorder, whose gene locus has been mapped tochromosome 8q22-q23, onset of obesity is in middle of childhood.

Clinical features include typical facieswith high nasal bridge, malar hypoplasia, short philtrum, prominentmaxillary central incisors and lips, and mild down-slanting palpebralfissures; narrow hands and feet with elongated fingers and toes;retinal degeneration with decreased vision; hypotonia; seizures;and mild mental retardation.

Prader-Willi Syndrome

Althoughthis disorder can occur in families, most instances are sporadic.

Clinical criteria for diagnosis havebeen described by Holm et al. (1993). These individuals have narrowface, almond-shaped eyes, small mouth with thin lips; developmentaldelay; mild to moderate mental retardation; and hyperphagia withobsessive food-seeking behavior. Obesity develops before 6 yrs ofage.

Deletions on proximal long arm of chromosome15 account for 70–80% of cases. The remainderare due to chromosome translocations and maternal uniparental disomy15. Fluorescence in situ hybridization (FISH) can detect the deletions.

Diagnostic Approach

If physicalexam and linear growth are normal, combination of genetic influencesand environmental factors is almost always the cause of obesity.

If decreased linear growth occurs,glucocorticoid excess, hypothyroidism, and growth hormone deficiencyshould be considered.

Many unusual syndromes associated withobesity may be distinguished by their clinical findings and moleculargenetic analysis.

References

1. Barlow SE, Dietz WH. Obesity evaluationand treatment: expert committee recommendations. Pediatrics 1998;102:29.
2. Behrman RE, et al., eds. Nelson textbook of pediatrics,16th ed. Philadelphia: WB Saunders, 2000.
3. CDC Growth Charts: United States. U.S. Department ofHealth and Human Services. Centers for Disease Control and Prevention.National Center of Health Statistics. Division of Data Services. Hyattsville,MD, 2001. World Wide Web URL: http://www.cdc.gov/growthcharts.
4. Charney E. The overweight child. In: Dershewitz RA,ed. Ambulatory pediatric care, 2nd ed. Philadelphia: JB Lippincott,1993:679–683.
5. Dietz WH. Health consequences of obesity in youth:childhood predictors of adult disease. Pediatrics 1998;101(suppl):518–525.
6. Dietz WH, Robinson TN. Assessment and treatment ofchildhood obesity. Pediatr Rev 1993;14:337–343.
7. Dietz WH, Robinson TN. Use of the body mass index (BMI)as a measure of overweight in children and adolescents. J Pediatr1998;132;191–193.
8. Farooqi S, O'Rahilly S. Recent advances inthe genetics of severe childhood obesity. Arch Dis Child 2000;83:31–34.
9. Hammer LD, Robinson TN. Child and adolescent obesity.In: Levine MD, Carey WB, Crocker AC, eds. Developmental-behavioralpediatrics, 3rd ed. Philadelphia: WB Saunders, 1999:370–379.
10. Himes JH, Dietz WH. Guidelines for overweight in adolescentpreventive services; recommendations from an expert committee. AmJ Clin Nutr 1994;"59:307–316.
11. Holm VA, et al. Prader-Willi syndrome: consensus diagnosticcriteria. Pediatrics 1993;91:398–402.
12. Leibel RL. And finally, genes for human obesity. NatureGenet 1997;16:218–220.
13. Michaud JL, et al. Natural history of Alstrom syndromein early childhood: onset with dilated cardiomyopathy. J Pediatr1996;128:225–229.
14. Online Mendelian Inheritance in Man (OMIM). McKusick-NathansInstitute for Genetic Medicine, Johns Hopkins University (Baltimore,MD) and National Center for Biotechnology Information, NationalLibrary of Medicine (Bethesda, MD), 2000. World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim.
15. Robinson TN. Defining obesity in children and adolescents:clinical approaches. Crit Rev Food Sci Nutr 1993;33:313–320.
16. Rosenbaum M, et al. Obesity. N Engl J Med 1997;337:396–407.
17. Rosner B, Pet al. Percentiles for body mass index inU.S. children 5 to 17 years of age. J Pediatr 1998;132:211–222.
18. Rudolph AM, ed. Rudoph's pediatrics, 20thed. Stamford, CT: Appleton & Lange, 1996.
19. Schonfeld-Warden N, Warden CH. Pediatric obesity: anoverview of etiology and treatment. Pediatr Clin North Am 1997;44:339–361.
20. Scriver CR, et al., eds. The metabolic and molecularbases of inherited disease, 8th ed. New York: McGraw-Hill, 2001.
21. Whitaker RC, et al. Predicting obesity in young adulthoodfrom childhood and parental obesity. N Engl J Med 1997;337:869–873.

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Book Source Details

• Book Title: The Diagnostic Approach to Symptoms and Signs in Pediatrics
• Author(s): Paul S. Bellet
• Year of Publication: 2006
• Copyright Details: The Diagnostic Approach to Symptoms and Signs in Pediatrics, Copyright © 2006 Lippincott Williams & Wilkins.

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More About This Book: Title: The Diagnostic Approach to Symptoms and Signs in Pediatrics Authors: Paul S. Bellet Publisher: Lippincott Williams & Wilkins Copyright: 2006 ISBN: 0-78172-899-1

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