We describe 5 Spanish children with Kabuki make-up syndrome (KMS)-3 females and 2 males-identified in Badajoz, Spain, between 1988 and 1990. All had the characteristic clinical and radiological manifestations of the syndrome. Psychomotor/mental retardation, postnatal growth deficiency, distinctive facial appearance, sagittal vertebral clefts, and dermatoglyphic abnormalities were present in all 5. Congenital heart defects were present in 4 patients. In addition, one had myopia, astigmatism, and bilateral paralysis of the VI cranial nerve. Another had apparent fusion of the hamate and capitate. An additional patient, as well as his mother, had an apparently balanced 15/17 translocation [46,XY,t(15;17) (15q;21q)]. The fact that these patients were ascertained in a catchment area of approximately 250,000 inhabitants and in a relatively limited period of time suggests that the prevalence of the KMS may be higher than previously recognized.

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BackgroundMucopolysaccharidosis type II (MPS II) is an inherited X-linked disease associated with a deficiency in the enzyme iduronate 2-sulfatase due to iduronate 2-sulfatase gene (IDS) mutations. Recent studies in MPS II carriers did not find clinical involvement, but these were mainly performed by anamnesis and patients’ self-reported description of signs and symptoms. So although it is rare in heterozygous carriers, investigations in other types of inherited X-linked disorders suggest that some clinical manifestations may be a possibility. The aim of this study was to evaluate the clinical pattern in female carriers of MPS II and to determine whether clinical symptoms were associated with the X-chromosome inactivation (XCI) pattern and age.MethodsFemale carriers of MPS II were genetically identified by molecular analysis of IDS. The clinical evaluation protocol included pedigree analysis, a comprehensive anamnesis, complete physical examination, ophthalmological evaluation, brain-evoked auditory response, electrocardiogram, echocardiogram, pulmonary function tests, abdominal sonogram, skeletal survey, neurophysiological studies, blood cell counts and biochemistry, urine glycosaminoglycan (GAGs) quantification, karyotype and pattern of XCI.ResultsTen women were included in the study. The mean age of the participants was 40.2 ± 13.1 years. Six carriers presented a skewed XCI pattern, 3 of whom (aged 38, 42 and 52 years) had increased levels of GAGs in the urine and showed typical MPS II clinical manifestations, such as skeletal anomalies, liver abnormalities, carpal tunnel syndrome, recurrent ear infection, hypoacusia and more frequent severe odontological problems without coarse facial features.ConclusionsThis is the first study performing a comprehensive evaluation of heterozygous MPS II carriers. Our results provide evidence of possible progressive, age-dependent, mild clinical manifestations in MPS II female carriers with a skewed XCI pattern, most likely affecting the normal allele. Further comparative studies with systematized clinical examinations in larger age-stratified populations of MPS II female carriers are required.