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Introduction Autoimmune polyglandular syndrome (APS) type 2 is characterized by the co-occurrence of several autoimmune endocrine diseases, including autoimmune thyroid disease, primary adrenal insufficiency, and type 1 diabetes mellitus. This [...]

X‐linked hydrocephalus with aqueductal stenosis (HSAS) is caused by mutation or deletion of the L1 cell adhesion molecule gene (L1CAM) at Xq28. Central diabetes insipidus (CDI) can arise as a consequence of resultant hypothalamic dysfunction from hydrocephalus and must be distinguished from nephrogenic diabetes insipidus (NDI) by exogenous vasopressin response. Causes of NDI are heterogeneous and include mutation or deletion of the arginine vasopressin receptor 2 gene (AVPR2), which is located ∼29 kb telomeric to L1CAM. We identified a patient with both HSAS and NDI where DNA sequencing failure suggested the possibility of a contiguous gene deletion. A 32.7 kb deletion mapping from L1CAM intron1 to AVPR2 exon2 was confirmed. A 90 bp junctional insertion fragment sharing short direct repeat homology with flanking sequences was identified. To our knowledge this is the first reported case of an Xq28 microdeletion involving both L1CAM and AVPR2, defining a new contiguous gene syndrome comprised of HSAS and NDI. Contiguous gene deletion should be considered as a mechanism for all patients presenting with hydrocephalus and NDI. © 2007 Wiley‐Liss, Inc.

We describe a 12-year-old boy with mosaic variegated aneuploidy (MVA), subnormal response to growth hormone (GH) stimulation testing, and short stature. In addition to features more commonly described in MVA such as microcephaly, cognitive deficits, and certain facial features, he also has features not commonly reported in MVA, including short limb segments, epidermoid cysts, ventricular septal defect, and subaortic stenosis. Chromosomal analysis revealed hyperdiploid chromosome numbers ranging from 47 to 70; modal number 50, in 24% of the metaphases. This case demonstrates that although the phenotype of MVA almost always includes growth failure, microcephaly, and mental retardation, additional features may vary greatly across individuals. His clinical features and course suggest that in addition to GH deficiency, he may have an intrinsic inability of the growth plate to respond to growth hormone. © 2002 Wiley-Liss, Inc.

Müllerian inhibiting substance is a gonadal peptide hormone that causes regression of the müllerian ducts in the male fetus and modulates Leydig cell proliferation and steroidogenesis in the postnatal testis. Determination of müllerian inhibiting substance has proven to be a useful diagnostic tool for assessment of the testes in children with nonpalpable gonads, including those with intersex conditions. Müllerian inhibiting substance measurement may also have clinical relevance for the evaluation of mature testicular function and spermatogenesis. Recent studies have confirmed a role for müllerian inhibiting substance as a tumor marker for ovarian tumors and in the histologic characterization of granulosa cell tumors and other sex cord tumors. One active area of clinical research is the potential pharmacologic applications of müllerian inhibiting substance in the fields of male infertility and oncology.

Müllerian inhibiting substance (MIS) is a gonadal peptide produced uniquely by Sertoli cells of the testis and granulosa cells of the ovary. In boys, serum MIS is low at birth, increases rapidly during the first year of life, then slowly declines thereafter until puberty. In girls, MIS is undetectable at birth, then rises minimally throughout childhood to a low pubertal peak. As a gonad-specific hormone with a sexually dimorphic pattern of expression, MIS has been recognized as having clinical applications that are relevant to the human reproductive system. Measurement of MIS in children with nonpalpable gonads and/or intersex disorders can help identify testicular tissue and assess testicular function. This is useful for the management of boys with cryptorchidism and for the diagnostic evaluation of children with intersex conditions. Moreover, the secretion of MIS by many sex-cord stromal tumors makes MIS determination beneficial for evaluating the completeness of surgical resection and for longitudinal screening of tumor recurrence in women with sex-cord tumors. MIS immunohistochemistry also may aid in the histologic diagnosis of ovarian tumors when conventional histology is ambiguous. Potential therapeutic uses of MIS that currently are being explored are based on employing its antiproliferative properties for chemotherapy of responsive tumors.

Objectives.In this study we evaluated changes in serum Müllerian inhibiting substance (MIS) concentration in a large number of patients with granulosa cell tumors (GCT) to determine whether MIS is elevated at the time of presentation and whether MIS is an index of successful surgical resection and management of recurrences.