Skip to Main Content

At a glance

A rare multiorgan syndrome with short stature, hypogonadism, severe mental retardation, and mitral valve prolapse (MVP).

Synonym

Hypogonadism Mitral Valve Prolapse Mental Retardation Syndrome.

Incidence

The exact incidence is not known, but this disorder is extremely rare.

Genetic inheritance

Not conclusive. Both X-linked recessive and autosomal recessive inheritance have been suggested.

Diagnosis

Based on the clinical findings of short stature, primary hypogonadism, MVP, and mental retardation. Most patients (approximately 80%) with MVP have a midsystolic click followed by a late systolic murmur; however, echocardiography is needed to confirm the diagnosis. However, due to its high sensitivity and specificity, cardiac MRI is increasingly used as a diagnostic tool. MVP describes the systolic displacement of mitral leaflet tissue into the left atrium past the mitral annular plane. Echocardiographic confirmation of MVP requires a single or bileaflet prolapse of at least 2 mm beyond the long-axis annular valvular plane into the left atrium during left ventricular systole, with or without thickening of the mitral leaflet. Classic MVP refers to thickening of the mitral leaflets more than 5 mm, while non-classic MVP describes mitral leaflets whose thickness is less than 5 mm. Myxomatous degeneration describes the pathologic accumulation of proteoglycans in the spongiosa layer of the mitral valve, the structural changes in all collagen components of the leaflet, and in the chordae tendineae. These changes can result in chordal rupture, a common finding in MVP.

Clinical aspects

These patients are typically mildly obese, have short stature and neck, and suffer from mild mental retardation. Other features include low-posterior hairline, downslanting of the palpebral fissures, a high-arched palate, bilateral cubitus valgus, and short fourth metacarpals. Primary hypogonadism manifests with small penis and small and atrophic testes, azoospermia, delayed puberty, gynecomastia, scant or absent facial hair, decreased body hair, and gynoid fat distribution. The low-normal plasma testosterone levels are unresponsive to stimulation with human chorionic gonadotropin (hCG). The baseline levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) are elevated with a mildly to moderately exaggerated response to gonadotropin releasing hormone (GnRH) and absent response to clomiphene. In addition, the increase in growth hormone (GH) after stimulation with growth hormone-releasing hormone (GHRH) is decreased, while plasma GH levels clearly rise in response to hypoglycemia. A hypothalamic-pituitary disorder associated with primary gonadal failure has been suggested. Mitral regurgitation with MVP is common. In otherwise healthy patients, symptoms of MVP may include fatigue, exercise intolerance, dyspnea episodes, recurrent chest pain, palpitations, syncopes, headache, sleep disorders, anxiety, panic attacks, and irritable bowel signs. The etiology of these symptoms is not well understood, but is most likely multifactorial, including autonomic dysfunction with adrenergic hyperresponsiveness and abnormal renin-angiotensin-aldosterone response to volume depletion. Patients often present with a low-resting blood pressure, which seems to be associated ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.