Nonspecific X‐linked mental retardation I: A review with information from 24 new families

Abstract

Clinical manifestations and other aspects of nonspecific X-linked mental retardation are reviewed using data from the literature and information on affected males in 24 new families ascertained in British Columbia. A great degree of variability was apparent in the mental abilities of affected males. Speech defects, other CNS disorders and minor physical changes such as "big" ears or a highly arched palate were not present in many cases. Evidence for the existence of a clinical entity of mental retardation associated with the fragile site at Xq27 or 28 and macro-orchidism is discussed. Genetic phenomena of reduced penetrance in males and of partial expression in females with respect of X-linked recessive genes are examined. Consideration is given to the question of whether this type of mental retardation is due to X-linked recessive or autosomal dominant sex-limited genes. Most ascertained cases of X-linked mental retardation are from families of northern European extraction. Recommendations are made regarding the diagnosis and counseling of X-linked mental retardation cases.

The fragile X syndrome: A study of 83 families

“…The fragile X syndrome was thus detected in more than 50% of the families with suspicion of X-linked mental retardation based on pedigree data. This proportion is in contrast with other authors (Herbst 1980) who found a higher percentage of the typical clinical syndrome in males of mar(X) negative families.…”

“…One hundred and thirteen of the 157 mar(X) male patients were postpubertal and 60% (see Table 2) manifested the typical triad: moderate mental retardation, long face and macroorchidism. This is in agreement with the findings of other authors (Sutherland & Ashforth 1979, Herbst 1980, Jacobs et al 1980, Jennings et al 1980, Herbst et al 1981, Mattei et al 1981, Carpenter 1983, Engel 1983, Jacobs et al 1983, Meryash et al 1984, Opitz & Sutherland 1984. In the clinically typical mar(X) male the face is long with large everted ears and mandibular prognathism, as well as a large quadrangular forehead with relative macrocephaly.…”

“…At the present time, the mar(X) chromosome has become the subject of increasing and wide-spread medical interest (Sutherland 1979, Sutherland & Ashforth 1979, Herbst 1980, Herbst & Miller 1980, Jacobs et al 1980, Turner & Opitz 1980, Herbst et al 1981, Mattei et al 1981, Blomquist et al 1982, Carpenter et al 1982, Venter & Op't Hof 1982, Blomquist et al 1983, Carpenter 1983, Fishburn et al 1983, Fryns & van den Berghe 1983, Glover 1983, Howard-Peebles 1983, Jacobs et al 1983, Kahkonen et al 1983, Brmdum-Nielsen et al 1983, Opitz & Sutherland 1984, Sherman et al 1984.…”

Fluency disorders in genetic syndromes

“…Ferrier, Bashir, Meryash, Johnston, and Wolff (1991) reported a mean percentage of stuttering of 4.9% in fragile X syndrome, 1.6% in autism and 6.1% in Down syndrome. Herbst (1980) recorded stuttering in only 3 out of 98 males with fragile X among 25 families. These figures should be interpreted cautiously, however, as their definition of "dysfluent" (nonfluent) speech differed from study to study.…”

The use of testicular volume as a clinical marker for cytogenetic disorders in mentally retarded males

“…The family pedigrees of karyotypically normal residents were subsequently examined for the presence of possible fra(X) negative non-specific XLMR. Pedigrees were postulated to show XLMR if they conformed to either of the following criteria (Herbst & Miller, 1980;Herbst, 1980;Fishburn et al, 1983): (1) affected males were present in at least two generations related through the mother of the proband; or (2) affected males were present in two sibships whose mothers were sisters. Pedigrees were excluded from X-linkage if the proband's MR was recorded as being due to: infections and intoxications; trauma or physical agents; disorders of metabolism, growth, and nutrition; gross postnatal brain disease; chromosomal abnormalities; and major psychiatric disorders (Herbst & Miller, 1980).…”