Clinical report
This newborn female was the first born by vaginal delivery, from healthy
non-consanguineous parents, at 40+2 weeks of gestation
after a naturally obtained and uneventful pregnancy. At birth her weight
was 3200 g (39th percentile), length 50 cm
(55th percentile), and occipitofrontal circumference
(OFC) 34.5 cm (64th percentile). She was transferred
on the second day of life from a first level birth center of the town,
because of feeding difficulties, hypotonia and dysmorphic features. On
admission to our Department she showed on physical examination: facial
asymmetry for hypoplasia of the left side of the face, low hairline,
broad nasal bridge, pear shaped tip of the nose and short columella,
small chin (Fig. 1a). Posteriorly-rotated left ear with thick helix,
homolateral preauricular tag and pit (Fig. 1b), as well as
inferotemporal epibulbar dermoid of the left eye and absent uvula were
observed. A sacral dimple was also noted (Fig. 2). Generalized hypotonia
and feeding difficulties completed her clinical profile. Brain
ultrasound (US) showed a corpus callosum narrowing, between the anterior
portion of the body and the genu. Abdomen and spinal cord US
examinations showed no abnormalities. US heart evaluation revealed a
subaortic ventricular septal defect. A whole spine X-ray was also
performed, and found lumbar kyphosis without vertebral defects.
Array comparative genomic hybridization (a-CGH) analysis (100–150 Kb
resolution, genomic assembly GRCh37.p13) identified a 2q13 deletion of
1.7 Mb, and indicated the positions 111,399,243 and 113,098,686 as the
breakpoints of the rearrangement. The deleted region involved different
genes, including partially BUB1 , ACOXL , BCL2L11 ,MIR4435-2HG , MIR4771-2 , ANAPC1 , MERTK ,TMEM87B , FBLN7 , ZC3H8 and ZC3H6 . a-CGH was
also performed in both parents, showing normal results and, thus,
confirming the de novo origin of the genomic abnormality.
The patient recovered from her initial feeding difficulties around the
seventh day of life. Hearing screening through transient-evoked
otoacoustic emissions (TEOAEs) revealed abnormal results. Then, an
audiological assessment to ascertain and characterize the hearing loss
was started. It included to date auditory brainstem response (ABR),
which showed a left unilateral moderately severe conductive hypoacusis.
She was discharged at 1 month of age after an otherwise uneventful
clinical course, and is included in a multidisciplinary
(neurodevelopmental, surgical, audiologic, ophthalmologic, cardiologic)
follow-up. She actually (3 months old) shows a mild developmental delay.