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Case Reports
. 2024 Feb 19;15(2):256.
doi: 10.3390/genes15020256.

Further Delineation of Clinical Phenotype of ZMYND11 Variants in Patients with Neurodevelopmental Dysmorphic Syndrome

Aleksandra Bodetko  1 , Joanna Chrzanowska  1 , Malgorzata Rydzanicz  2 , Agnieszka Borys-Iwanicka  3 , Pawel Karpinski  4 , Joanna Bladowska  5   6 , Rafal Ploski  2 , Robert Smigiel  1
Affiliations
Case Reports

Further Delineation of Clinical Phenotype of ZMYND11 Variants in Patients with Neurodevelopmental Dysmorphic Syndrome

Aleksandra Bodetko et al. Genes (Basel). .

Abstract

Intellectual disability with speech delay and behavioural abnormalities, as well as hypotonia, seizures, feeding difficulties and craniofacial dysmorphism, are the main symptoms associated with pathogenic variants of the ZMYND11 gene. The range of clinical manifestations of the ZMYND phenotype is constantly being expanded by new cases described in the literature. Here, we present two previously unreported paediatric patients with neurodevelopmental challenges, who were diagnosed with missense variants in the ZMYND11 gene. It should be noted that one of the individuals manifested with hyperinsulinaemic hypoglycaemia (HH), a symptom that was not described before in published works. The reason for the occurrence of HH in our proband is not clear, so we try to explain the origin of this symptom in the context of the ZMYND11 syndrome. Thus, this paper contributes to knowledge on the range of possible manifestations of the ZMYND disease and provides further evidence supporting its association with neurodevelopmental challenges.

Keywords: ZMYND11; diazoxide; hyperinsulinaemic hypoglycaemia; neurodevelopmental dysmorphic syndrome.

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Conflict of interest statement

The authors declare no conflicts of interest. The corresponding author has informed all authors of the journal’s conflict of interest policy.

Figures

Figure 1
Figure 1
Brain MR examinations of patient 1: axial T1-weighted images (A,C) and axial T2-weighted images (B,D) performed at the age of 6 months (upper row) and at the age of 14 months (bottom row). The images show a feature of cortico-subcortical atrophy with an adjacent enlargement of the subarachnoid space in the fronto-temporal areas ((A,B)—red arrows). There is also delayed myelination of the white matter, indicating a typical pattern for the age of 4 months ((A)—white arrow pointing to a high signal intensity of the splenium of the corpus callosum on the T1-weigthed image). The follow-up MRI examination (C,D) revealed progression of the myelination process; the cortex/white matter differentiation is blurred, especially on the T2-weighted image ((D)—red arrows), instead of being clearly visible at this age, which can indicate a demyelination disorder.
Figure 2
Figure 2
Facial phenotype of patient 1 at 6 months of age.
Figure 3
Figure 3
Brain MR examination of patient 2: axial T1-weighted image (A), axial (B) and coronal (C) T2-weighted images, as well as SWI image (D). The T1- and T2-weighted images (A–C) suggest delayed myelination of the cerebral white matter, indicating a stage of myelination typical for the age of 8 months. There is also dilatation of the ventricular system and cerebral sulci as a sign of cerebral cortico-subcortical atrophy. The MRI also showed a cavum septum pellucidum (C). The SWI sequence (D) did not reveal any low signals of hemosiderin depositions.
Figure 4
Figure 4
Results of continuous glucose monitoring in patient 2: at diagnosis of hyperinsulinaemic hypoglycaemia (A) and during treatment with diazoxide (B).
Figure 5
Figure 5
Facial phenotype of patient 2 with a ZMYND11 variant at 22 months of age.
See this image and copyright information in PMC

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