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Deletion 22q11 syndrome: acknowledging a lost eponym as we say farewell to an acronym

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Editor—Time may be closing on use of the acronym “CATCH22” for “deletion 22q11 syndrome”,1 but it is likely to be a good while before it has finally run out. Many will prefer to retain their personal preference and “deletion 22q11 syndrome” does not easily roll off the tongue (and it really needs to be stated in full to distinguish it from the separate and emerging “deletion 22q13 syndrome”2 3). Besides this, any consensus accepted by geneticists will take time to filter through to colleagues in other disciplines who, carrying most of the clinical burden for managing the patients' medical problems, may reasonably question the value of so much discussion about a name. Before (if ever) the relatively unambiguous “deletion 22q11 syndrome” achieves universal acclaim, and/or “velocardiofacial syndrome” (VCFS), the history of medical genetics should record that a little known otolaryngologist from Prague, Dr Eva Sedláčková, almost certainly described the syndrome in 1955,4 and subsequently in 1967,5 as a result of good clinical observation on a cohort of patients with congenital shortening of the soft palate. The findings are further referred to in a paper on soft palate innervation.6 The first paper, of course, appeared some 10, 13, 23, and 25 years before publications by DiGeorge,7 Shprintzen et al,8 Strong,9 and Takaoet al,10 respectively. With medical and scientific publications dominated by the English language, the publication of Sedláčková's work in her native Czechoslovakian was always likely to pass unnoticed, a problem compounded by the consequences of cold war politics. However, the similarity of Sedláčková's cases to VCFS has previously been noted by one of us (RWP)11 and also acknowledged in a major text.12 Sedláčková herself, who died in 1976 aged 62, attempted to achieve some recognition for describing the condition that subsequently became known as VCFS (R J Gorlin, personal communication).

In the first and most important description of a syndrome with congenitally short velum,4 Sedláčková highlighted many of the features characterising deletion 22q11 syndrome. Between 1950 and 1954, 26 children, 11 boys and 15 girls, were identified with a shortened soft palate and a sufficiently long hard palate but no clefting. They ranged in age from 2 to 16 years and their appearance was so distinctive that it was known the child would “snuffle” even before it spoke. Nine of the children were poor feeders because of a weak suck and motor development was delayed in all but two. Only seven began speaking at the normal age, while the others typically began to speak in their third or fourth years. The facial features were described as striking, with narrow, slanting eye slits, a degree of telecanthus, an open mouth, a wide base to the nose, and a fairly flat nose with small nostrils. The upper lip was described as being short and drawn up, the philtrum somewhat smooth, and there was a degree of micrognathia. In addition, ear lobes were described as small, the entrance to the auditory meatus narrow, and otitis media was common. In 22 of the 26 children the hands were described as small and slender, the fingers being short and slim with pointed ends. Terminal phalanges, in particular, were short. Growth was generally satisfactory, with the exception of three cases who were noticeably shorter and weaker than their sibs. Occasional abnormalities included mild contraction of the fingers (n=1), overlapping toes (n=2), unilateral oligosyndactyly of the right hand (n=1), congenital subluxation of the hip (n=2), Sprengel deformity (n=1), and undescended testes (n=3). Mental retardation to some degree was noted in nine of the 26. By the time of her second paper,5Sedláčková had gathered 48 cases, noted an imperfect closure of the eyelids in some, and added congenital heart disease to the list of associated anomalies. Her syndrome became known as velofacial hypoplasia.13

Most significantly, Sedláčková provided illustrations of typical cases with a congenitally shortened velum in her first paper,4 including two examples with frontal portrait view. In her second paper a further portrait of a typical case is provided.5 Clinicians who know deletion 22q11 syndrome could surely not dispute the patients having facies well within the spectrum with which we are now familiar. It seems likely she described children across the DiGeorge-VCFS spectrum, as a short philtrum with tented upper lip tends to be part of DiGeorge syndrome, while slender, tapering fingers tend to be associated with VCFS. However, she made no mention of long fingers, which is generally the pattern in VCFS, and herein lies the only obvious discrepancy. Nevertheless, the illustrations of hands from typical cases4 is acceptably within the spectrum for deletion 22q11 syndrome. She has not included children with overt clefting but this probably reflects her ascertainment of cases, perhaps not wanting to potentially “contaminate” the cohort by including those operated on for cleft palate. She does, however, refer to 10 cases with congenitally short palate, operated on for cleft palate, from the huge series of more than 2600 cases operated on by the late Professor Burian.4 One cannot, of course, exclude the possibility that she described some non-deletion 22q11 cases because today, with the benefit of a reliable test, phenocopies are sometimes observed in genetic clinics.

Overall, the close overlap of Sedláčková's description, together with the illustrative material, is convincing, but expert readers must decide for themselves whether she has reported what we now know as deletion 22q11 syndrome. If the subjects could be revisited and FISH tested, the controversy would be resolved but the passage of time perhaps makes this unlikely. There has been work showing a common aetiology of velofacial hypoplasia and VCFS,14 but no suggestion that any of Sedláčková original cases were included. Given the prevalence of deletion 22q11 syndrome, any clinician with a substantial case load of velopharyngeal insufficiency is bound to have a cohort with the condition; it is then a matter of distinguishing these from other cases. We suggest that Sedlácková successfully achieved this, provided a good clinical description, and should be acknowledged for the accomplishment.

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