Syndromic Hearing Loss in Association with PTPN11-Related Disorder: The Experience of Cochlear Implantation in a Child with LEOPARD Syndrome
A 5-year-old girl visited our hospital because of bilateral hearing loss. She was born at 32 weeks of gestation with a birth weight of 2,100 g via a vaginal delivery. On the newborn hearing screening test, she was diagnosed as having bilateral hearing loss. At 9 months of age, she had an operation for pulmonary stenosis. In the first year of life, dysorexia with feeding difficulty developed, which was caused by oromotor trouble, and this added to the development of ambulation disorder. Finally, she was diagnosed as having cerebral palsy and she has been maintained on rehabilitation therapy since then. The family history was not remarkable.\nPhysical examination revealed hypertelorism, a plane occiput and low-set ears (). She also had numerous symmetrically distributed dark brown macules involving the face, scalp, upper extremity, axilla and trunk. A transthoracic ECG for preoperative evaluation showed slightly increased left ventricular (LV) wall thickness with normal LV contractility. Any auditory brainstem response was not detected in either of the ears. The auditory steady-state response showed responses with 120 decibel (dB) at 1 kHz and 115 dB at 2 kHz on the left side, and 125 dB at 4 kHz on the right side. Based on the audiological evaluation as described above, she was diagnosed with bilateral profound hearing loss. Bilateral enlarged vestibular aqueducts (EVA) were identified on the computed tomography (CT) of the temporal bone and magnetic resonance imaging (MRI) of the internal auditory canal, but both the internal auditory canal were observed to be of normal size, as well as the cochlea and the semicircular canals, which were normally filled with fluid on both sides ().\nTo investigate the etiology of the hearing loss and the other physical abnormalities of the patient, molecular study for the PTPN11 gene was performed based on the clinical diagnosis of LS. Informed consent was obtained from her parents. DNA was extracted from peripheral leukocytes according to the standard protocols. All the coding exons and intron-exon boundary sequences of the PTPN11 gene were bidirectionally sequenced using the Big Dye Terminator ABI Prism Sequencing Kit (Applied Biosystems, Foster City, CA, USA) and the ABI PRISM 3100 Genetic Analyser (Applied Biosystems). As a result, the patient was found to be heterozygous for a missense mutation in exon 12. This mutation was a G-to-A transition at nucleotide position 1,381 and it was predicted to substitute the 461st residue alanine to threonine (c.1381G>A, p.Ala461Thr) (). The family study revealed that neither of the asymptomatic parents was carrying the mutation, indicating the de novo occurrence of the mutation.\nThe patient received CI in the left ear (Nucleus Freedom). The electrode was completely inserted in the scala tympani, and neural response telemetry (NRT) during the operation showed good results. The patient was able to respond to loud sound, but she still could not deliver meaningful communication on her last follow-up visit 1 year after CI, and her score on the CAP scale conformed to Category 1.