A new patient with the rare ICF syndrome (immunodeficiency, centromeric heterochromatin instability, and facial anomalies) is reported. The six patients previously reported in the literature are reviewed. The main clinical and cytogenetic characteristics of the syndrome are discussed.

Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 inframe small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene.

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Epidemiological studies have suggested that non-specific X-linked mental retardation (XLMR) might be at least as frequent as the fragile X syndrome. The identification of all mutations causing XLMR would thus appear of prime importance. In the absence of other clinical signs the problem of genetic heterogeneity is acute. This can be partly overcome by the analysis of large families. We have been able to perform linkage analysis in 3 such families. The condition in family 1 was described as clinically resembling the fra (X) syndrome by Proops et al [1983]: the kindred includes 7 affected males in 3 sibships. Family 2 from Denmark has affected males in 4 generations; however, several affected relatives in this extended pedigree are deceased. Family 3 from France counts 6 affected males in two sibships. The families were analysed with about 25 X-linked markers. Linkage with markers in Xp22.2-p22.3 was found in family 1: z(theta) = 2.62 at theta = 0.06 for DXS85 (probe 782). Suggestion of linkage was found in family 2 with both the Duchenne muscular dystrophy region (DXS164 in Xp21.2) and with DXS1 (Xq11-q12). In family 3, DXS159 (Xq12-q13) gave a lod score of 2.53 at theta = 0; results were compatible with localisation of the putative XLMR locus in this family proximal to DXYS1 (Xq21). These data suggest that at least two non-specific XLMR loci could exist, one in Xp22 and the other in the q12-q13 region.

BackgroundAn increase in cryptorchidism has been reported in many countries. One mechanism could be low fetal testosterone production possibly secondary to altered placental human chorionic gonadotrophin (hCG) release. Our Objective was to compare hCG values from maternal blood between boys with cryptorchidism and normal boys.MethodsTotal hCG and α-fetoprotein (AFP) values [12–16 weeks of gestation; from the double test for Down syndrome screening) were compared between cases of cryptorchidism and normal control boys who were matched for maternal age, maternal smoking, gestational age at time of hCG measurement (±1 day), birth weight and birth term. Measurements were performed in a single laboratory; values were expressed as absolute values (KU/L) and multiples of the median (MoM). Boys whose mothers had had a complicated pregnancy were excluded. Groups were compared using the Student’s t test. Log transformation was used to normalize hCG, MoM hCG, AFP and MoM AFP distribution, and values were expressed as geometric means (-1, + 1 tolerance factor).ResultsTotal hCG and MoM hCG levels were significantly lower in the 51 boys with cryptorchidism compared to 306 controls (21.4 (12.3; 37) KU/L vs 27.7 (15.9; 47.9) KU/L and 0.8 (0.5; 1.2) MoM vs 1.0 (0.6; 1.6) MoM, respectively, p < 0.01). By contrast, AFP and MoM AFP levels were similar between groups.ConclusionThis study showed a link between low maternal serum hCG levels and cryptorchidism in boys from uncomplicated pregnancy, while normal AFP levels indicated a normal fetoplacental unit. Whether these abnormalities were due to endogenous or exogenous factors remains to be determined.