Clinical and genetic characteristic of patients with Pitt–Hopkins syndrome

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Abstract


Background. Pitt–Hopkins syndrome (PHS) is the rare inherited disease, caused by a microdeletion on chromosome 18q21 or heterozygous mutation TCF4 gene and characterized by severe mental retardation, abnormal breathing patterns: hyperventilation, apnea, and unusual facial features.

Material and method. We examined 9 children, included 4 boys and 5 girls at the age of 1 year 8 months to 12 years with PHS. All children have clinical symptoms characteristic of this syndrome. The diagnosis was confirmed by Array CGH (deletion of genomic material in chromosomal region 18q21) and new generation sequencing.

Results. Microdeletions chromosome 18 (18q21) were identified in 5 patients. The size of the microdeletions varied from 307 Kb to 11.62 Mb. A point mutation was detected in 4 children: two patients had a mutation in the splicing site, 1 — missense and 1 — nonsense-mutation. The clinical picture was analyzed in all children: psychomotor retardation, severe intellectual disability, poor speech, autistic behavior, hypotonia, and specific phenotype.

Conclusion. Comparative analysis of the clinical picture in patients with PHS, caused by a microdeletion on chromosome 18q21 and point mutation in the TCF4 gene showed that no significant clinical differences were found. The main clinical criteria for suspecting PHS are gross developmental delay, severe delayed psychomotor development, behavioral disorders, and episodes of hyperventilation with the subsequent apnea.


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About the authors

Olga B. Kondakova

National Medical Research Center for Children's Health

Author for correspondence.
Email: kondakova.ob@nzcd.ru

Russian Federation, Moscow

Dmitry I. Grebenkin

National Medical Research Center for Children's Health

Email: kondakova.ob@nzcd.ru

Russian Federation, Moscow

Anastasiya A. Lyalina

National Medical Research Center for Children's Health

Email: kondakova.ob@nzcd.ru

Russian Federation, Moscow

Evgeniya V. Krustaleva

Scientific and Practical Center for Child Psychoneurology

Email: kondakova.ob@nzcd.ru

Russian Federation, Moscow

Ilya V. Kanivets

Genetic Center «Genomed»

Email: kondakova.ob@nzcd.ru

Russian Federation, Moscow

Tatiana T. Batysheva

Scientific and Practical Center for Child Psychoneurology

Email: kondakova.ob@nzcd.ru

Russian Federation, Moscow

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Supplementary files

Supplementary Files Action
1.
Fig. 1. Phenotype of the PHS patient The photo is published with the permission of the parents.

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2.
Fig. 2. MRI of the brain in of the PHS patient aged 8 years. 1 — reduction in size and configuration of hippocampi (red arrow), frontal T2-weighted image; 2 — corpus callosum dysplasia (white arrow), cerebellar atrophy (yellow arrow), sagittal T1-weighted image; 3 — cerebellar atrophy (yellow arrow), axial T2-weighted image.

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Copyright (c) 2020 Kondakova O.B., Grebenkin D.I., Lyalina A.A., Krustaleva E.V., Kanivets I.V., Batysheva T.T.

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