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At a glance

An frequently lethal disease in infants characterized by cardiac and urogenital anomalies.

Synonyms

Najjar Syndrome; Malouf Syndrome; Genital Anomaly-Cardiomyopathy Syndrome; Congestive Cardiomyopathy with Hypergonadotropic Hypogonadism; Dilated Cardiomyopathy with Premature Ovarian Failure; Cardiomyopathy with Primary Testicular Failure; Genital Anomaly with Cardiomyopathy.

Incidence

Less than 20 patients have been described.

Genetic inheritance

Autosomal recessive inheritance has been suggested. Parental consanguinity seems to be a significant risk factor. The defect seems to be caused by mutations in the LMNA gene (Lamin A) that has been mapped to chromosome 1q22. Lamin mutations are involved in a variety of diseases, often referred to as laminopathies, such as ☞Charcot-Marie-Tooth Disease Type 2, ☞Emery-Dreifuss Muscular Dystrophy, ☞Limb-Girdle Muscular Dystrophy Type 1B, ☞Köbberling-Dunnigan Syndrome, ☞Progeria Syndrome (Hutchinson-Gilford Syndrome), dilated cardiomyopathy Type 1A, and mandibuloacral dysplasia. Lamins are structural protein components of the nuclear membrane that convey a multitude of functions, ranging from structural support of the nucleus (nuclear pores) to facilitating chromatin organization, gene regulation, and DNA repair. The nuclei of cells lacking lamin A (or C) are more fragile and less resistant to mechanical strain and exhibit altered mechanotransduction signaling.

Diagnosis

Based on the clinical findings and family history. There is significant phenotypic heterogeneity observed among the reported cases and it is unclear if that reflects an underlying genetic heterogeneity of this disorder.

Clinical aspects

Urogenital features include hypergonadotropic hypogonadism with minimal or absent pubertal development. Males may present with primary testicular failure, hypospadias/epispadias, micropenis, cryptorchidism or testicular atrophy, and bifid hypoplastic scrotum. Females may present with ovarian dysgenesis, hypoplastic uterus, and amenorrhea. All patients suffer from dilated cardiomyopathy (myofiber disarray) with cardiac dysfunction (often complicated by arrhythmias) that may be rapidly progressive and severe already in early infancy, but more commonly with onset in the second or third decade of life. These patients will eventually require a heart transplant to avoid death from cardiac failure. Additional features may include hypothyroidism, diabetes mellitus, hypertriglyceridemia, hyperuricemia, blindness, blepharoptosis, deafness, broad nasal bridge, anodontia, protruding lips, thoracic scoliosis, arachnodactyly, decreased sweating, decreased body hair, and mental retardation.

Precautions before anesthesia

Assess cardiac function and review and optimize treatment for cardiac failure preoperatively. Obtain and review electrocardiogram and echocardiography examinations and consult with a cardiologist if possible. Depending on the severity of cardiac involvement and the planned intervention, a postoperative stay in the intensive care unit will be required and should be arranged beforehand. Preoperative blood work should at least include serum electrolytes, creatinine, and urea as these patients will most likely be on diuretics (and/or β-blockers and angiotensin-converting enzyme inhibitors). If a pacemaker is in place, its function should be checked and the best intraoperative management option discussed with an electrophysiologist. Developmental delay (particularly when combined with ...

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