Townes-Brocks syndrome: detection of a SALL1 mutation hot spot and evidence for a position effect in one patient.

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.

Acromesomelic dwarfism: a new variation.

The rate skeletal disorder, acromesomelic dwarfism, is characterized by short stature and short limbs. Bone dysplasia is evident. We report two cases of a variation of this disorder in a Portuguese woman and her son. The clinical features of these two cases differ from those of cases previously reported in the literature.

Townes-Brocks syndrome. Report of a case and review of the literature.

The authors report a new case of Townes-Brocks syndrome with cardiac defect, ossicular anomalies and dominant transmission. The intrafamilial variability of the phenotype and the difficulty of diagnosis in isolated cases are underlined.

[West's syndrome. A clinical, therapeutic and prognostic study. Apropos of 66 cases]. / Le syndrome de West. Etude clinique, thérapeutique et pronostique. A propos de 66 observations.

The charts of 66 children suffering from West syndrome followed by the paediatric department of the University Central Hospital, Lille, between 1957 and 1984 were reviewed: 24 cases were followed for more than 10 years; 20 cases from 5 to 10 years; 22 cases from 1 to 5 years. Age at onset of the disease ranged from 3 to 5 months (37.8%) and 6 to 8 months (30.3%) with a slight male predominance. Prenatal causes were the most important (42.4%) with anomalies and cerebral malformations in 15.2% and neurocutaneous syndromes in 9.1% of cases. Etiology remained unknown in 27.3% of cases. Some clinical aspects were characteristic (flexion or extension spasms, psychomotor retardation) in 84.8% of cases. Hyparrhythmia occurred in 62.1% of cases. There were no significant differences in the results of the varying therapies used (ACTH, Synacten, hydrocortisone) or its associations. The best results were obtained with a treatment started as early as possible in the cryptogenic forms and in older infants (6 to 8 months).

[Ectrouria. Apropos of a case]. / L'ectrourie. A propos d'une observation.

Report of a case of sirenomelia (mermaid) anomaly. This male fetus was born from a 30 year-old mother and remained alive for 18 hours. The following anomalies were present: Potter's syndrome, absence of external genitalia and internal genital ducts, presence of two male gonads, renal agenesis, lack of bladder and ureteral ducts, single umbilical artery. Were also found: right radial dysplasia, Fallot tetralogy, T.E. fistula with esophageal atresia, lumbo-sacral spina bifida cystica.

[Robinow's syndrome with dominant transmission]. / Syndrome de robinow à transmission dominante.

Robinow syndrome in a mother and her 2nd male infant. Clinical and radiological findings were characteristic of this condition. Hands and spine were normal in the proband, but humerus were short. In this case, as in Robinow's first description, genetic transmission was autosomal dominant.