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This study was undertaken to document the phenotype of Kabuki (Niikawa-Kuroki) syndrome in patients from Australia and New Zealand, with particular emphasis on growth patterns, behavior, and relationship between head circumference and intellectual level. Data on 27 children and adults with Kabuki (Niikawa-Kuroki) syndrome from Australia and New Zealand were collected by questionnaire and clinical assessment. The patients ranged in age from 7 months to 36 years with a mean age of 7 years and 2 months. The mean age at diagnosis was 3(5/6) years, but in most cases, the facial phenotype was evident from infancy. The minimum birth prevalence was calculated at 1 in 86,000. Three of our patients died. Parents reported a behavior phenotype characterized by an excellent long-term memory and avoidance of eye contact. No correlation was found between head circumference and severity of intellectual disability. Eight of 14 patients over the age of 5 years were overweight or obese. Six of these eight patients had failure to thrive in infancy. One patient developed insulin-dependent diabetes mellitus in adolescence. Some individuals with Kabuki (Niikawa-Kuroki) syndrome show a characteristic growth profile with failure to thrive in infancy progressing to obesity or overweight in middle childhood or adolescence. A behavior phenotype was noted which requires further investigation. Head size is not a predictor of degree of intellectual disability.

The Birth Defects/Congenital Malformations Register of the Victorian Department of Human Services contains detailed, confidential information on over 2,000 babies born with a birth defect each year in Victoria, Australia, representing approximately 3% of the annual number of births. For 1991 and 1993, the type of anomaly was categorised as warranting a high, moderate, or low need of referral for genetic counselling, depending on risk of recurrence and possible genetic cause. The Victorian Clinical Genetics Service at the Murdoch Institute, Melbourne, offers free, centralised genetic counselling services for the entire state. A comparison of case records between the two agencies has shown little difference in overall use of genetic counselling between 1991 (17%) and 1993 (16%). Rate of uptake in the "high need" category improved only slightly during that period, from 40% in 1991 to 43% in 1993. Utilization of genetic counselling services did not vary disproportionately with mother's country of birth, but was higher for older mothers. As was expected, rates were highest when a baby was born at the only hospital that provides on-site genetic counselling services. Even where a statewide genetic counselling service is in place, it is disappointing that over half of those judged at high need for genetic counselling are not making use of this service. This study will provide baseline information to which future studies can be compared. Using the same study methodology, it will be possible to examine whether the uptake rate increases in accordance with increased genetic services.

Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnancies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time.

Record linkage between a prenatal diagnosis register and a congenital malformation register in the state of Victoria, Australia, has enabled further evaluation of the suggested association between limb deficiencies and early chorion villus sampling (CVS). We found 3 anomalies in this category after later CVS (i.e., 9 weeks and beyond), but our data suggest that advanced maternal age may be a risk factor for both terminal and all limb deficiencies. The data from Victoria are tabulated with data obtained from other registers. Different birth prevalence figures are obtained by different registers, therefore limiting comparisons between registers. © 1993 Wiley-Liss, Inc.

A prospective study of the fragile X syndrome [fra(X)] was initiated one year ago to refine the estimates of recurrence risks based on the phenotype of the mother and the family history of the syndrome. The basic unit of data consists of the description of the conceptus of women known to carry the fra(X) gene or of mothers of an isolated case. To date, information on 261 women and their conceptuses was ascertained primarily through prenatal diagnosis; these data are summarized here. Although tests of significance were limited due to small sample sizes in subgroups, the following trends were observed: 1) the penetrance of fra(X) site expression was 80% in both male and female conceptuses suggesting that fra(X) site expression is equally penetrant early in development; 2) the sex ratio at the time of prenatal diagnosis did not differ from one, indicating that selection against fra(X) fetuses, if any, does not differ among sexes; 3) the recurrence risk among offspring of borderline/mildly retarded mothers was higher than that among offspring of intellectually normal mothers; 4) the recurrence risk in offspring did not differ based on the mother's fra(X) site expression; and 5) the recurrence risk in offspring of mothers with isolated cases was slightly less (34%) than that of obligate carrier mothers (41%) although this was not significant. The potential use of these prospective data on the fra(X) syndrome is emphasized.

Three families with confirmed and one family with suspected male transmission of the fragile X are presented, with psychological and physical assessment of all available members. The psychological tests used were the Peabody Picture Vocabulary test and Block Design which measured verbal and non-verbal abilities, respectively. Physical status was assessed by recording dysmorphic features and by anthropometric measurements. This study demonstrated that there are appreciable differences in mental and physical status within sibships of daughters of male carriers, as well as recognizable physical alterations and intellectual impairment in the transmitting males. These fmdings contradict the concept that there are two distinct categories of fragile X carriers: phenotypically normal as opposed to affected. They suggest instead that the defect may be graded and emphasize the importance of intellectual deficits and physical alterations in defining the fragile X phenotype, both in low-penetrant males and female heterozygotes.