Okamoto syndrome in a girl of Caucasian origin

Abstract

We report the clinical and genetic evaluation of a 2-year-old Greek female with striking phenotypic similarities to the three previously published cases of Okamoto syndrome. The main features were characteristic facies, cleft palate, generalized hypotonia, severe developmental delay, congenital hydronephrosis, and congenital heart defects. Routine chromosome testing and whole-genome high-resolution comparative genetic hybridization analysis were negative for any gross numerical or structural chromosome aberrations and for microdeletions/duplications of more than 3 million base pairs respectively. Fluorescence in situ hybridization analysis for 22q11.2 deletion and DNA analysis of the protein tyrosine phosphatase, non-receptor type II gene were normal, thus excluding DiGeorge and Noonan syndromes. Our patient did not show most of the cardinal features of Schinzel-Giedion, otopalatodigital, and C-trigonocephaly syndromes. Moreover, in our patient some new malformations were identified: unilateral kidney hypoplasia and severe anal stenosis. The latter was considered as pertinent and is described here to establish a wider clinical spectrum of Okamoto syndrome. At the age of 3 years 6 months the child continues to show severe growth failure and significant global developmental delay. For the practising paediatrician it is prudent to bear Okamoto syndrome in mind, especially in children with learning disability and a pattern of dysmorphic features.

A newborn with likely Okamoto syndrome

“…Her pattern of congenital anomalies and dysmorphic features fits well within the clinical spectrum described in the four earlier reported cases of Okamoto syndrome (Okamoto et al, 1997;Wallerstein et al, 2005;Markouri et al, 2008).…”

“…Since then, two further case reports have been published (Wallerstein et al, 2005;Markouri et al, 2008). We propose that the proband represents the fifth reported case.…”

“…Thus, hydronephrosis in association with PUJ obstruction is a rare manifestation of the Kabuki syndrome. Bilateral congenital hydronephrosis secondary to PUJ obstruction has been reported in all cases of Okamoto syndrome with the exception of one case that was unilateral with the other kidney being significantly hypoplastic (Markouri et al, 2008).…”

“…However, the measurements provided in two reports (Okamoto et al, 1997;Wallerstein et al, 2005) show that all of the growth parameters at the time of reporting (6-30 months) were low and the head circumference was in keeping with the weight and length. Microcephaly was mentioned in the report of Markouri et al (2008) but no growth measurements were provided.…”

A new autosomal dominant syndrome of distinctive face showing ptosis and prominent eyes associated with cleft palate, ear anomalies, and learning disability

“…A search for the combination of cleft palate and Noonan-like features shows a rare condition named Okamoto syndrome which consists of multiple congenital anomalies, developmental delay, and characteristic facial features [Okamoto et al, 1997;Markouri et al, 2008;Taylor and Aftimos, 2010]. The condition was described in five patients, two of them of Caucasian origin.…”