A new compound heterozygous mutation in a female with 17α-hydroxylase/17,20-lyase deficiency, slipped capital femoral epiphysis, and adrenal myelolipoma.

17α-Hydroxylase/17,20-lyase deficiency (17-OHD) is a rare disease caused by mutations of the CYP17A1 gene. Slipped capital femoral epiphysis (SCFE) rarely occurs in adults. There are occasional reports of adrenal myelolipoma (AML) in 17-OHD. A 27-year-old Chinese female (46, XX) visited the hospital for SCFE and presented with continuous hypokalemia, absent spontaneous puberty, and hypertension. Hypergonadotropic hypogonadism was detected. The laboratory tests were consistent with 17-OHD. AML was considered based on the imaging examinations. A mutation analysis of the CYP17A1 gene identified the following compound heterozygous mutation: a frame-shift mutation, i.e. c.985_987delTACinsAA (p.Tyr329fs), that had been reported to be a common mutation in the Chinese population was found in exon 6. Another new nonsense mutation, i.e. c.1270C > T (p.Gln424*), that causes a premature termination codon was found in exon 8. Treatment with prednisone had poor efficacy. The administration of 0.75 mg dexamethasone and estradiol/dydrogesterone cyclic treatment significantly improved the patient's symptoms. For the first time, we report a 17-OHD case accompanied by SCFE, AML, and a novel mutation site in the CYP17A1 gene. We provide insight into the clinical manifestations, genetic analysis, and treatment options of 17-OHD.

A familial case series of valgus slipped capital femoral epiphysis.

We present a familial case of valgus slipped capital femoral epiphysis (SCFE). Charts of members of the same family having the condition were retrieved. Clinical and radiological examinations were conducted after 10 years of the initial presentation and treatment. Two siblings, brother and sister, were initially diagnosed with valgus SCFE and treated surgically. Normal clinical examination was found for both siblings and both, treated and untreated hips. A radiological examination for the parents revealed signs of valgus SCFE in both hips of the mother. No association with metabolic, hormonal or neurological conditions was found. The review of the literature demonstrated that varus SCFE has a strong familial tendency. Our case series would suggest that, as in the classical SCFE, genetic inheritance could also be a contributing factor to valgus SCFE. Future radiological studies are needed to look for the true incidence of valgus SCFE in first- and second-degree relatives.

Microarray analysis of slipped capital femoral epiphysis growth plates.

BACKGROUND: Microarray technology has been used to analyze gene expression in patients with and without slipped capital femoral epiphysis (SCFE). METHODS: Proximal femoral physis core biopsies from two patients with SCFE were compared with two control specimens from age-matched patients without SCFE. Extracted RNA from frozen ground samples was subjected to microarray analysis with data tests for statistical significance between SCFE and control tissues. RESULTS: Compared to controls, SCFE samples demonstrated significant up-regulation in gene expression pathways involving physiological defense and inflammatory responses and significant down-regulation in the regulation of cellular physiologic processes, cellular metabolic pathways, and skeletal development pathways including expression of aggrecan and type II collagen, genes affecting physeal structure and integrity. CONCLUSIONS: Up-regulation of inflammatory and immune response pathways in SCFE compared to controls relates to physeal mechanical displacement in SCFE. Globalized down-regulation of several other pathways suggests growth plate weakening. These novel microarray findings further define SCFE etiology.

Three cases of slipped capital femoral epiphysis in one family.

Slipped capital femoral epiphysis is a relatively common disorder of the hip that affects children in late childhood and early adolescence, with an incidence in the United States of approximately 10 per 100,000. Although the diagnosis and treatment of slipped capital femoral epiphysis have been well described, the search for its cause and a method of early identification continues. Recent publications have suggested that there is a familial association among individuals with slipped capital femoral epiphysis, but there is no current genetic marker established for the disorder. This article reports a series of 3 biologically related Caucasian sisters who were athletic; had body mass indices <26 kg/m(2); had no record of any hormonal imbalances or endocrine abnormalities; had good nutrition; and presented with atypical characteristics of slipped capital femoral epiphysis. This is the first report of a series of 3 sisters with slipped capital femoral epiphysis in the United States. Our goals were to document our experience in the identification and treatment of these patients to highlight the complexities of slipped capital femoral epiphysis presentation patterning, to increase the awareness and reporting of familial cases of slipped capital femoral epiphysis by other physicians, and to encourage additional research in this area. As clinicians progress in the ability to diagnose and treat patients with slipped capital femoral epiphysis, they also must be mindful of the varying presentation characteristics.