Open Access Case report

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

Gerarda Cappuccio1, Alessandro Rossi1, Paolo Fontana1, Emma Acampora1, Valeria Avolio1, Giuseppe Merla2, Leopoldo Zelante2, Aurelio Secinaro3, Generoso Andria1 and Daniela Melis1*

Author Affiliations

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

2 Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy

3 Bambino Gesù Children Hospital, IRCCS, Rome, Italy

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BMC Medical Genetics 2014, 15:15  doi:10.1186/1471-2350-15-15

Published: 28 January 2014



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.


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.

Kabuki syndrome; Isomerism; Respiratory distress