Melnick‐Needles syndrome is a rare putative X‐linked dominant bone dysplasia. The patients have short stature, characteristic facial features, and a normal intelligence. The skeletal dysplasia includes S‐shaped curvature of tubular bones and sclerosis of the base of the skull. The phenotype of affected individuals varies, even within families. This could be related to X chromosome inactivation. We report here on a very mildly affected mother and her two severely affected daughters with characteristic features of Melnick‐Needles syndrome. In addition, the two daughters had very similar pigmented nevi on their back. X chromosome inactivation analysis of blood DNA revealed a skewed X inactivation pattern in all three affected females, with the normal X chromosome as the predominating active X chromosome. The X inactivation pattern was similar in buccal smear and blood DNA in the mother and one of the daughters, whereas the other daughter had a skewed pattern in blood only. X chromosome inactivation in blood and buccal smear DNA therefore does not explain the phenotypic variation in this family. The skewed X chromosome inactivation is in agreement with X‐linked inheritance of Melnick‐Needles syndrome and suggests a critical role of the Melnick‐Needles gene in hematopoietic cell proliferation. Clinical evidence indicates that Melnick‐Needles syndrome is allelic to the otopalatodigital syndromes, which have been assigned to Xq26‐28. Haplotype analysis of the X chromosomes in this family was in agreement with the localization of the gene for Melnick‐Needles syndrome to Xq25‐qtel. © 2002 Wiley‐Liss, Inc.

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The Multidimensional Impact of Cancer Risk Assessment (MICRA) is a new tool to measure the specific impact of result disclosure after genetic testing. The authors compared its performance with that of questionnaires measuring general and cancer-specific distress. Participants (158 women) responded 1 month after they received genetic test results. The women were divided into 4 standard clinical test result groups: BRCA1/2 positive, BRCA1/2 negative, panel negative, and true negative. Factor analysis supported the formation of 3 subscales: Distress (6 items, alpha = .86), Uncertainty (9 items, alpha = .77), and Positive Experiences (4 items, alpha = .75). All 3 MICRA subscales differentiated participants who were BRCA1/2 positive from the other 3 groups. MICRA thus helps identify subgroups of vulnerable genetic testing participants.

The purpose of this study was to validate the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire. The FACT/GOG-Ntx is the FACT-G plus an eleven-item subscale (Ntx subscale) that evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy. Two groups of women with ovarian cancer completed the FACT/GOG-Ntx: one group with known neurotoxicities and one group of chemotherapy-naive women newly diagnosed with ovarian cancer. Levels of patient neuropathy, severity of toxicity, and patient quality of life from diagnosis of ovarian cancer to 12 months post-diagnosis were assessed. The Ntx subscale significantly differentiated the two groups at baseline and 3- and 6-month follow-ups, demonstrating significantly fewer problems among chemotherapy-naive patients than among patients with known neuropathy. The FACT/GOG-Ntx is a reliable and valid instrument for assessing the impact of neuropathy on health-related quality of life. The Ntx subscale demonstrated sensitivity to meaningful clinical distinctions and change over time.