Unexpected occurrence of xeroderma pigmentosum in an uncle and nephew.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by a decreased ability to repair DNA damaged by UV radiation and the early development of cutaneous and ocular malignant neoplasms. Approximately 20% of patients with XP also develop progressive neurologic degeneration. OBSERVATIONS: We describe a boy who was found to have XP after a severe burn following minimal sun exposure. His maternal uncle, now age 20 years, had been diagnosed with XP after a similar sunburn in infancy. The uncle has the typical skin pigmentary findings of XP along with severe progressive neurologic involvement. Although the infant's parents were not known to be blood relatives, the infant and his affected uncle proved to be compound heterozygotes for the same 2 frameshift mutations in the XPA DNA repair gene (c.288delT and c.349_353del). After the diagnosis of XP in the infant, genealogic investigation identified a common Dutch ancestor for both of his grandfathers 5 generations back. CONCLUSIONS: Counseling families at risk for a rare inherited disease is not always straightforward. The sociocultural and demographic backgrounds of the families must be considered for evaluation of risk assessment.

Ectopic thymus presenting as a thyroid nodule in a patient with the Carney complex.

Ectopic thymic tissue within the thyroid gland is rare. Patients with a complex of myxomas, spotty skin pigmentation, and endocrine overactivity, collectively known as Carney complex (CNC), have a predisposition towards the development of thyroid abnormalities, but there are no reports of thymic defects in CNC. We present the case of a 12-year-old boy with CNC and a growing thyroid nodule. The patient had the c.682 C > T (Arg228X) pathogenic PRKAR1A mutation. Hemithyroidectomy for a Hürthle cell adenoma led to the confirmation of distinct intrathyroidal ectopic thymic tissue. Thymic abnormalities have not been previously reported in CNC.

Detection of adrenocorticotropin-secreting pituitary adenomas by magnetic resonance imaging in children and adolescents with cushing disease.

CONTEXT: We recently showed that pre- and postcontrast spoiled gradient-recalled acquisition in the steady-state (SPGR) was superior to conventional pre- and postcontrast T-1 weighted spin echo (SE) acquisition magnetic resonance imaging (MRI) for the diagnostic evaluation of pituitary tumors in adult patients. OBJECTIVE: The present investigation assessed the use of SPGR vs. SE-MRI in the diagnostic evaluation of ACTH-secreting tumors in children and adolescents with Cushing disease. DESIGN: Data were analyzed retrospectively from a series of patients seen over 7 yr (1997-2004). SETTING: The setting for this study was a tertiary care referral center. PATIENTS: Thirty children with Cushing disease (13 females and 17 males with a mean age of 12 +/- 3 yr) were studied. INTERVENTIONS AND OUTCOME MEASURES: Imaging results were compared with surgical and pathological findings and the clinical outcome. RESULTS: Twenty-eight patients had microadenomas, and two had macroadenomas; the latter were identified by both MRI techniques. Precontrast SE and SPGR-MRI identified four and six of the microadenomas, respectively. Postcontrast SPGR-MRI identified the location of the tumor in 18 of 28 patients, whereas postcontrast SE-MRI identified the location and accurately estimated the size of the tumor in only five patients (P < 0.001). CONCLUSIONS: We conclude that conventional MRI, even with contrast enhancement, mostly failed to identify ACTH-secreting microadenomas in children and adolescents with Cushing disease. Postcontrast SPGR-MRI was superior to SE-MRI and should be used in addition to conventional SE-MRI in the pituitary evaluation of children and adolescents with suspected Cushing disease.

Pathology and molecular genetics of the pituitary gland in patients with the 'complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas' (Carney complex).

Carney complex (CNC) is a familial multiple neoplasia and lentiginosis syndrome with features overlapping those of McCune-Albright syndrome (MAS) and other multiple endocrine neoplasia (MEN) syndromes like MEN type 1 (MEN 1). Pituitary tumors have been described in a number of patients with CNC; all have been growth hormone (GH) and prolactin (PRL)-producing. In at least some patients, pituitary gland involvement is manifested by hyperplastic areas; hyperplasia appears to involve somatomammotrophs only and to precede GH-producing tumor formation, in a pathway similar to that seen in MAS-related pituitary tumors (and in oncogenesis in other CNC tissues). One patient with CNC and advanced acromegaly had a GH-producing macroadenoma that showed extensive genetic changes at the chromosomal level. These changes appeared to represent secondary or tertiary genetic 'hits' involved in pituitary oncogenesis and were confirmed at the molecular level. So far, almost half of the patients with CNC have germline-inactivating mutations in the PRKAR1A gene; in their pituitary tumors, the normal allele of the PRKAR1A gene is lost. Loss of heterozygosity suggests that PRKAR1A, which codes for the regulatory subunit type 1alpha of the cAMP-dependent protein kinase A (PKA), may act as a tumor-suppressor gene in pituitary tissue. These data provide evidence for a PKA-induced somatomammotroph hyperplasia in the pituitary tissue of CNC patients; hyperplasia leads to additional genetic changes at the somatic level, which in turn cause the formation of adenomas in some, but not all, patients.