Bronchial isomerism in a Kabuki syndrome patient with a novel mutation in MLL2 gene

BMC Medical Genetics

Daniela Melis³  Generoso Andria³  Aurelio Secinaro²  Leopoldo Zelante¹  Giuseppe Merla¹  Valeria Avolio³  Emma Acampora³  Paolo Fontana³  Alessandro Rossi³  Gerarda Cappuccio³ 

[1]Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy

[2]Bambino Gesù Children Hospital, IRCCS, Rome, Italy

[3]Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy

关键词: Respiratory distress;    Isomerism;    Kabuki syndrome;   

Others  :  1122521
DOI  :  10.1186/1471-2350-15-15

 received in 2013-05-21, accepted in 2014-01-07,  发布年份 2014

【 摘 要 】

Background

Kabuki syndrome (KS) is a rare, multiple congenital anomalies/intellectual disability syndrome caused by mutations of MLL2 gene, which codifies for a histone methyltrasferase that regulates the embryogenesis and the tissue development. Left-bronchial isomerism is a rare congenital abnormality that can be defined as the absence of the normal lateralizing features which distinguish right and left-sides in the lungs. To date, this is the first report of left-bronchial isomerism in association with KS.

Case presentation

A one-month-old Caucasian male patient underwent our attention for microcephaly, dysmorphic features (long palpebral fissures, eyebrows with sparse lateral third, everted lower eyelids, blue sclerae, large dysplastic ears, lower lip pits), persistent fetal fingertip pads, short stature, heart defects (interventricular defect and aortic coarctation), unilateral cryptorchidism, hypotonia and delay in gross motor skills. These features suggested a diagnosis of KS and a molecular analysis confirmed a novel frame-shift mutation in the exon 11 of MLL2 gene. Subsequently, given recurrent respiratory infections with a normal immunological status, he underwent a chest CT scan that showed a left bronchial isomerism.

Conclusion

We report a patient affected by KS, with a novel MLL2 mutation and an atypical phenotype characterized by left-side bronchial isomerism. Interestingly, genes involved in the heterotaxia/isomerism such as ROCK2 and SHROOM3 are known to interact with MLL2 gene. In order to achieve a correct diagnosis and an appropriate therapy, the presence of pulmonary anatomical variations should be investigated in KS patients with respiratory signs not associated to immunological deficiency. Finally, our findings support the hypothesis that the mutations leading to a complete loss of function of MLL2 gene is often associated with complex visceral malformations.

【 授权许可】

   
2014 Cappuccio et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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