Although the presence of Y-specific DNA generally results in a more masculinized phenotype, exceptions do occur. In the Y-DNA-negative group, complete or incomplete masculinization in the absence of SRY suggests a mutation of one or more downstream non-Y, testis-determining genes.

The actual worldwide incidence of congenital hypothyroidism (CH) is based on the results of screening in parts of the world where screening is mandatory, i.e. most of Europe, USA, Canada, Cuba, Australia, New Zealand and Japan. In other parts of the world, some indications are given by the results of pilot studies. In Europe, mean overall incidence (1985-1990) for the countries included in our inquiry is 1/3801 – in each country for the same period: Austria 1/3,930, Belgium 1/3,750, Czechoslovakia 1/6,037, Denmark 1/3,777, Finland 1/3,969, France 1/4,132, FRG 1/3,827, Greece 1/3,314, Hungary 1/5,632, Israel 1/3,152, Italy 1/3,150, The Netherlands 1/3,723, Norway 1/3,069, Portugal 1/3,139, Spain 1/3,216, Switzerland 1/3,913, UK 1/3,398 and Turkey (pilot study 1989-1992) 1/2,943. In comparison, the figures for the USA for the whole country are similar for the mean overall incidence (1988-1990): 1/4,119. But large variations exist between the states, the reasons of which are perhaps related either to technical problems or to the ethnic background in each state. In Canada and Japan, modifications of screening procedures have led to similar figures for the last years in our possess, Canada (1986-1988) 1/3,884 and Japan (1990) 1/3,856. The figures (mean overall incidence) for Cuba (1987-1991) 1/2,325, for Australia (1985-1990) 1/1/3,331 and for New Zealand (1987-1990) 1/4,496 are quite comparable. So in these countries where the screening is established, no great variations are noted as in certain parts of the world with pilot studies: Argentine (Buenos Aires; 1985-1990) 1/4,407, Chile (1991-1992) 1/2,514, Brazil (Porto Alegre; 1987-1991) 1/4,429. In Mexico (1990-1991), it is 1/1,480; however, the overall incidence is higher, in the two pilot studies carried out in Ecuador. On the other hand, a pilot study carried out in São Paulo (1982-1991) on 1,794,051 tests is 1/14,352; the low incidence should be related to the ethnic background or/and techniques of screening.

Townes-Brocks syndrome (TBS) is an autosomal dominant developmental disorder characterized by anal and thumb malformations and by ear anomalies that can affect the three compartments and usually lead to hearing loss. The gene underlying TBS, SALL1, is a human homolog of the Drosophila spalt gene which encodes a transcription factor. A search for SALL1 mutations undertaken in 11 unrelated affected individuals (five familial and six sporadic cases) led to the detection of mutations in nine of them. One nonsense and six different novel frameshift mutations, all located in the second exon, were identified. Together with the previously reported mutations [Kohlhase et al., 1999], they establish that TBS results from haploinsufficiency. The finding of de novo mutations in the sporadic cases is consistent with the proposed complete penetrance of the disease. Moreover, the occurrence of the same 826C>T transition in a CG dimer, in three sporadic cases from the present series and three sporadic cases from the other series [Kohlhase et al., 1999] (i.e., six of the eight mutations identified in sporadic cases), reveals the existence of a mutation hotspot. Six different SALL1 polymorphisms were identified in the course of the present study, three of which are clustered in a particular region of the gene that encodes a stretch of serine residues. Finally, the chromosome 16 breakpoint of a t(5;16)(p15.3;q12.1) translocation carried by a TBS-affected individual was mapped at least 180 kb telomeric to SALL1, thus indicating that a position effect underlies the disease in this individual.

Even though a subgroup of patients may require a higher dosage of L-thyroxine, an initial dosage of 7.5-8.0 micrograms/kg per day, with an early assessment of FT4, FT3, and TSH levels, is adequate for the treatment of the majority of infants with congenital hypothyroidism.

Objective: To determine between timing and LT4 dose which was the more important factor for IQ at 7 years in screened congenital hypothyroidism (CH). Methods: 131 children with CH born from 1979 to 1994 and 30 controls were studied. Mean age at recall: 22.8 ± 1.1 days. Mean initial LT4: 5.6 ± 0.1 µg/kg/day. Results: Optimal global IQ (GIQ; 119.0 ± 1.8) was obtained for a recall ≤15 days. Results for a recall after 3 weeks were lower (107.7 ± 2.4). The IQ of infants treated before 21 days (117.1 ± 1.2) was identical to the IQ of controls (117.0 ± 2.3) whereas the IQ of those treated after this threshold was lower (108.6 ± 1.7). No significant differences for GIQ were observed with various initial LT4 doses. Infants treated with a dose of LT4 ≧6 µg/kg/day had a higher performance IQ (117.3 ± 1.8 vs. 112.8 ± 1.2) compared with those treated with a dose <6 µg/kg/day. The severity of CH and socio-economic levels were similar in all groups. Conclusion: In this study, timing appears to be the more important factor for the intellectual outcome.