Vasquez Hurst Sotos syndrome
Overview
A rare genetic disorder characterized by underdeveloped genitals, obesity, mental retardation and skeletal abnormalities.
Symptoms
* Mental retardation * Mild skeletal defects * Deafness * Concentration difficulties * Learning difficulties * Dysmorphic facies * Hypogonadism * Hypotonic facies * Renal anomalies * Incomplete development of genitals * Small penis * Undescended testes * Reduced muscle tone * Siezures * Enlarged male breasts * Obesity * Short stature * Skeletal defects * Abnormal curvature of the spine * Mental retardation
Causes
* Pubertal –Prevalence 40–69% in adolescent males –Onset by 10–12 years old –Peaks at 13–14 years, Tanner III staging –Resolution in 1–2 years in 75% –Obese patients more affected * Several drugs can cause gynecomastia –Antiandrogens: Flutamide, finasteride, ketoconazole, spironolactone –GI agents: Cimetidine, ranitidine –Calcium channel blockers: Verapamil, nifedipine –Illicit drugs: Marijuana, heroin, methadone, amphetamines –Hormones: Androgens, anabolic steroids, estrogens –Psychiatric: Phenothiazines, diazepam, tricyclic antidepressants o Androgen insufficiency –Klinefelter syndrome (47, XXY) –Seminiferous tubule dysgenesis –Testicular failure –Androgen-insensitivity syndrome, androgen receptor defects –Biosynthetic defects in testosterone production –Isolated LH deficiency * Excess estrogen –Feminizing adrenocortical tumors (rare) * Testicular neoplasms –Germ cell tumors: Associated with hCG production; hCG leads to Leydig cell dysfunction and increased aromatase –Leydig cell tumors secrete estradiol –Sertoli cell tumors: Associated with excessive aromatase activity o Pseudogynecomastia –Fat deposition without glandular development –Seen in obesity o Other breast enlargement (not true gynecomastia) –Neurofibroma –Carcinoma of breast –Hemangioma –Lipoma * Reifenstein syndrome * Kallmann syndrome * Liver cirrhosis
Diagnosis
A urine drug screen and thyroid profile should be done at the outset. Liver function studies, liver biopsy, and serum iron and iron-binding capacity will help rule out hemochromatosis and cirrhosis of the liver. A serum FSH, LH, HCG, and estradiol will help diagnose testicular tumors, Klinefelter's syndrome, and testicular feminization syndrome. Further evidence of Klinefelter's syndrome is obtained by a buccal smear (Barr bodies). Normal gonadotropin and sex hormone levels make serious pathology unlikely. A serum cortisol, cortisol suppression test, and rapid adrenocorticotropic hormone (ACTH) test will help diagnose Cushing's syndrome and Addison's disease. There is a specific beta-HCG assay that can be done to rule out an HCG-secreting tumor such as carcinoma of the lung.
Treatment
o Pubertal –No treatment if pubertal development and physical exam are normal –Re-evaluation in 6 months * Cessation of drugs when implicated * Testosterone replacement if indicated for hypogonadism * Weight loss for pseudogynecomastia * Surgery (reduction mammoplasty) if severe and psychologically distressing * Persistent pubertal gynecomastia –Therapy is investigational; no large trials completed yet –Antiestrogens (clomiphene and tamoxifen) –Aromastase inhibitors (testolactone)