Array-CGH in patients with Kabuki-like phenotype: Identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration

Ivon Cuscó,Mireia Vilardell,Blanca Gener,Miguel Del Campo,Enrique Galán,Laura Toledo,Luis A Pérez-Jurado,Eva González

doi:10.1186/1471-2350-9-27

Abstract

BackgroundKabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown.MethodsWe have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited.ResultsNo duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group.ConclusionOur results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.

Highlights

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads
All referring physicians filled out a basic clinical datasheet and sent pictures of their patients. They all shared at least some of the facial features of KS that lead to the suspicion of this diagnosis along with mental retardation
A major conclusion of our study is that we were unable to find any common rearrangement causally related to KS

Summary

Introduction

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. KS is characterized by specific facial features including long palpebral fissures with eversion of the lateral one-third of the lower eyelid, arched eyebrows with sparseness of the lateral third, a short columella with a depressed nasal tip and prominent ears. This syndrome includes mild to moderate mental retardation, postnatal growth retardation with final short stature, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. No consensus diagnostic criteria have been established yet, but based on the clinical findings reported by Niikawa et al [1] five cardinal manifestations were defined to include patients in the KS group (peculiar face, skeletal anomalies, dermatoglyphic abnormalities, mild to moderate mental retardation and postnatal growth deficiency)

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