Sharing genetic risk with next generation: mutation-positive parents' communication with their offspring in Lynch Syndrome.

Identification of hereditary predisposition to cancer has limited significance if not followed by efficient cancer prevention. The responsibility of informing offspring about genetic risk often falls to the parents. We systematically investigated how parents with Lynch Syndrome share knowledge of genetic risk with their offspring, challenges in the communication process and wish for professional support. Of all known mutation carriers over age 40 (n = 337) in 102 Finnish Lynch Syndrome families, 86% completed a self-reported questionnaire; 248 of them (86%) had children. Of the 248 parents, 87% reported disclosure and 13% nondisclosure. Reasons for nondisclosure were mainly the young age of offspring, socially distant relationships, or feeling of difficulty in discussing the topic. Men reported significantly more often disclosure with a support person (spouse etc.) (P < 0.001). The most difficult communication aspect was discussing children's cancer risk. Of the 191 firstborn adult children informed, 69% had taken the predictive genetic test. Every third parent suggested that health professionals should be involved in passing on the information and that a family appointment at the genetic clinic should be organized at the time of disclosure. Nearly all parents had informed their adult offspring about the genetic risk and possibility of genetic testing, but almost one-third were unsure of how their offspring had used the information. The challenge is to improve the communication processes, so that all offspring would get the information important for their health care, and parents would get the professional support desired at disclosure.

A familial CHARGE syndrome with a CHD7 nonsense mutation and new clinical features.

The autosomal dominant CHARGE syndrome (MIM musical sharp214800) is caused by mutations in the CHD7 gene. It is usually sporadic but a few cases with gonadal mosaicism and familial inheritance have been reported. We describe a familial CHARGE syndrome in a two-generation Finnish family with a nonsense mutation in the CHD7 gene. Detailed clinical examination of the affected family members was performed, and mutations in the CHD7 gene were analysed with direct sequencing and multiplex ligation-dependent probe amplification. A nonsense mutation, p.Q1599X, was detected in exon 21 of the CHD7 gene in three affected family members. The father was only mildly affected, whereas his son had a very severe manifestation of the syndrome, causing death at the age of 3 months. The second pregnancy was prematurely terminated in the 23rd week because of cardiac anomalies detected in the ultrasound scan. The father's brother also had mild symptoms, but no mutation was detected in him. In this report, the variability of clinical symptoms within families and the clinical importance of mildly affected patients with the CHARGE syndrome are underlined with implications for molecular genetic diagnostics of the syndrome. Features not described in the CHARGE syndrome before are also presented.

Dysmorphic facial features in aspartylglucosaminuria patients and carriers.

The facial photos of 76 aspartylglucosaminuria (AGU) patients, 29 obligate carriers and 78 unrelated controls were evaluated for dysmorphic features to see whether this autosomal recessive lysosomal storage disease includes a dysmorphic facial gestalt in addition to the well-known age-related coarsening of the facies and whether the carrier status of AGU might have an effect on the facial features. A consistent dysmorphic gestalt with hypertelorism, a short and broad nose with round nares, simple often small ears with small or missing lobule and modest folding of helices, thick lips and a square shape of face, was found to be present long before the coarsening begins. Recognition of this pattern of facial features might help in the early diagnosis of AGU. Statistically, puffy eyelids were found to be significantly more frequent in AGU carriers than in controls. These findings support an earlier implication that AGU carrier status might have a slight influence on the phenotype.

Hypertrichosis, hyperkeratosis, abnormal corpus callosum, mental retardation and dysmorphic features in three unrelated females.

We report three unrelated patients with hypertrichosis, mild to moderate mental retardation, and dysmorphic facial features including low anterior hairline, thick arched eyebrows, nose with broad tip and columella below alae nasi, short philtrum, thick drooping lower lip and simple posteriorly rotated ears. They also had rough skin with hyperkeratotic plaques. Feet and finger tips were broad. All of them had personality problems like aggressiveness, stubborn temperament or tendency to withdraw. Brain MRI showed thick and short corpus callosum. We believe that these patients represent a new syndrome of unknown aetiology.