Kabuki syndrome and sex chromosomal anomalies: Is it really an association?

25 11 2008


To the Editor:

Kabuki syndrome (KS), described by Niikawa (1) and Kuroki (2), occurs in about 1 in 32,000 newborns (3) and is characterized by specific facial dysmorphism, mild to moderate mental retardation, short stature, skeletal abnormalities, prominent fingertip pads and a probably autosomal dominant inheritance. The patients that partially overlap these manifestations are included in the KS-like phenotype group. Up to now, no genetic basis was established, even if several cytogenetic abnormalities detected by karyotype, CGH and FISH have been reported. In particular, an association with different sex chromosomal anomalies (SCA) was reported.

Turner syndrome (TS), occuring in about 50 per 100,000 girls, is defined by a partially or completely absent X-chromosome (4). The majority of TS patients have a 45,X karyotype; moreover short- or long-arm deletion, ring X, isochromosome and mosaicism were reported. The cardinal features include growth retardation with reduced adult height with or without additional features like minor facial dysmorphism, associated anomalies, gonadal insufficiency and infertility (4). Coarctation of aorta (CoA) is the commonest congenital heart disease both in KS and in TS.

We have rewieved our database on 8 KS, 32 TS and 16 other sex chromosome anomalies (47,XXX; 47,XXY and 47,XYY) cases and we did not find an association between the two conditions. We also evaluated 6 isolated CoA cases and we did not find clinical signs evocative of one of the two conditions (KS or TS).

We do not agree with the conclusion by Chen et al (5) that “Kabuki syndrome, a peculiar facial appearance and aortic coarctation, should be considered in girls with sex chromosome abnormalities.” The reported case should be included in the KS-like phenotype group, in which, while several possible associations were reported, evidence was insufficient to confirm an association between the two conditions. This point is of great importance in genetic counselling of patients with SCA, especially prenatally, where in the presence of an SCA diagnosis the couple has to make the decision to continue or voluntarily terminate the pregnancy. In recent years, long-term follow-up of prenatal and postnatal SCA cases reduced voluntarily aborted cases. More knowledge of the real role of this and other associations between different genetic conditions is important in prenatal decision making and in genetic counselling. Finally, we agree that genetic evaluation should be performed for KS patients, especially in patients with overlapping phenotypes, because genetic characterization may provide clues to the final identification of the molecular basis of specific syndromes.

Sebastiano Bianca 
Barbara Barrano
Antonella Cataliotti
Lara Indaco
Carmela Ingegnosi
Centro di Consulenza Genetica e di Teratologia della Riproduzione
Laboratorio di Citogenetica
Dipartimento Materno Infantile
ARNAS Garibaldi Nesima
Catania, Italy

Giuseppe Ettore
2UOC Ginecologia e Ostetricia
Dipartimento Materno Infantile
ARNAS Garibaldi Nesima
Catania, Italy

1. Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 1981;  99: 565-9.

2. Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr 1981; 99: 570-3.

3. Adam MP, Hudgins L. Kabuki syndrome: a review. Clinical Genetics 2004; 67: 209-19.

4. Gravholt CH. Epidemiological, endocrine and metabolic features in Turner syndrome. Europ J Endocrinol 2004; 151: 657–87

5. Chen CP, Lin SP, Tsai FJ,Chern SR, Wang W. Kabuki syndrome in a girl with mosaic 45,X/47,XXX and aortic coarctation. Fertil Steril 2008; 89: 1826.e5–7.


Published online in Fertility and  Sterility   DOI: 10.1016/j.fertnstert.2008.12.112




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