Severe clinical presentation in monozygotic twins with 10p15.3 microdeletion syndrome

Abstract

Submicroscopic deletion of 10p15.3 is a rare genetic disorder, currently reported in 21 unrelated patients. It is mainly associated with cognitive deficits, speech disorders, motor delay and hypotonia. The size of the deleted region ranges between 0.15 and 4 Mb and does not generally correlate with phenotype. A monozygotic female twin pair with a de novo 2.7 Mb deletion of 10p15.3 is herein reported. The girls presented at the age of 8 months with severe developmental delay and failure to thrive since the first month of life. Their perinatal and family history was unremarkable. On admission they both exhibited generalized dystonia, microcephaly, complete absence of voluntary movements and visual/auditory unresponsiveness. Their brain MRIs demonstrated dilatation of ventricles, subarachnoid spaces and anterior interhemispheric fissure and sylvian fissures bilaterally. Cranial radiography revealed partial fusion of both coronal sutures. Visual and brainstem auditory evoked potentials were markedly abnormal, indicating severe visual and sensorineural hearing impairment. The electroencephalogram, as well as a screening for inborn errors of metabolism, were unremarkable. Both patients required gastrostomy and tracheostomy before the age of 1 year. They were, additionally, managed with physical therapy, as well as baclofen and low-dose haloperidol. Their current state at the age of 2 years is relatively stable. The index patients' phenotype includes features, such as dystonic cerebral palsy, visual and sensorineural hearing impairment or craniosynostosis, which have not been previously reported in individuals with 10p15.3 deletion. It is necessary to consider these novel clinical features and investigate their possible relationship with the recently recognized syndrome.

A de novo missense mutation in ZMYND11 is associated with global developmental delay, seizures, and hypotonia

“…Figure 3B shows all previously reported variants of ZMYND11 and Supplemental Table 2 presents the full phenotypic comparison with all other reported ZMYND11 variants. Sensorineural hearing loss has been reported in 10p15.3 microdeletion syndrome but is not commonly described in these patients (Vargiami et al 2014). It is unclear whether the bilateral sensorineural hearing loss in this patient is due to an independent genetic cause other than ZMYND11 .…”

Clinical description of a neonate carrying the largest reported deletion involving the 10p15.3p13 region

“…Microdeletion syndrome 10p15.3 has only recently been described in a small number of patients. Because only 25 cases of microdeletion syndrome 10p15.3 have been reported to date and clinical data were obtained for only 17 of the 23 published cases, extremely limited information is available for clinical phenotype. Microdeletion syndrome 10p15.3 has common phenotypes including cognitive/behavioral delay, language impairments, motor delay, craniofacial dysmorphism, brain anomalies, and seizures.…”

Infantile spasms with periventricular nodular heterotopia, unbalanced chromosomal translocation 3p26.2 ‐10p15.1 and 6q22.31 duplication

“…Affected genes in our patient, that is, the genes in the deletions and duplications of our patient in chromosomal bands 10p15. 5 Review of the literature identified 18 cases with 10p15.5-p15.1 deletions in size equal to or smaller than our patient's, of whom, 13 had adequate clinical descriptions [7,8]. All 13 cases had developmental delay and two had seizures but none had periventricular nodular heterotopia or infantile spasms [7,8].…”

“…5 Review of the literature identified 18 cases with 10p15.5-p15.1 deletions in size equal to or smaller than our patient's, of whom, 13 had adequate clinical descriptions [7,8]. All 13 cases had developmental delay and two had seizures but none had periventricular nodular heterotopia or infantile spasms [7,8]. There was one case with a 3p26.3-p26.2 duplication who presented with intellectual disability and seizures in the second year of life but had no periventricular nodular heterotopia or infantile spasms [9].…”