A novel pathogenic variant in the DYNC1H1 gene: the combining neuromuscular and brain involvement in the disease spectrum of “Dyneinopathyes”. A case report.

Angela La Tempa

A novel pathogenic variant in the DYNC1H1 gene: the combining neuromuscular and brain involvement in the disease spectrum of “Dyneinopathyes”. A case report.

Autori

ANGELA LA TEMPA (UO MALATTIE NEUROMUSCOLARI DELL’ETÀ EVOLUTIVA, UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY ; UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY; DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE (DIMEC), UNIVERSITÀ DI BOLOGNA, ITALY. – NEUROPSICHIATRIA INFANTILE (SPECILIZZANDA))
FEDERICA TRENTIN (UO MALATTIE NEUROMUSCOLARI DELL’ETÀ EVOLUTIVA, UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY; UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY; DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE (DIMEC), UNIVERSITÀ DI BOLOGNA, ITALY. – NEUROPSICHIATRIA INFANTILE (SPECIALIZZANDA))
GIULIA GUARDI (UO MALATTIE NEUROMUSCOLARI DELL’ETÀ EVOLUTIVA, UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY; UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY; DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE (DIMEC), UNIVERSITÀ DI BOLOGNA, ITALY. – NEUROPSICHIATRIA INFANTILE (SPECIALIZZANDA))
MELANIA GIANNOTTA (UO MALATTIE NEUROMUSCOLARI DELL’ETÀ EVOLUTIVA, UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY – NEUROPSICHIATRIA INFANTILE)
FLAVIA PALOMBO (PROGRAMMA DI NEUROGENETICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY. – NEUROGENETICA)
AHMED SHEIK MAYE HODMAN (PROGRAMMA DI NEUROARDIOLOGIA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY – NEURORADIOLOGIA)
LAURA LICCHETTA (UOC CLINICA NEUROLOGICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA – NEUROLOGIA)
MARIA LUCIA VALENTINO (UOC CLINICA NEUROLOGICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA – NEUROLOGIA)
ROSARIA PLASMATI (UOC NEUROLOGIA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY – NEUROLOGIA)
DUCCIO MARIA CORDELLI (UO MALATTIE NEUROMUSCOLARI DELL’ETÀ EVOLUTIVA, UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY; DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE (DIMEC), UNIVERSITÀ DI BOLOGNA, ITALY. – PEDIATRIA)
ANTONELLA PINI (UO MALATTIE NEUROMUSCOLARI DELL’ETÀ EVOLUTIVA, UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY – NEROPSICHIATRIA INFANTILE)

Presentatore

ANGELA LA TEMPA (UO MALATTIE NEUROMUSCOLARI DELL’ETÀ EVOLUTIVA, UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY 2 UO NEUROPSICHIATRIA DELL’ETÀ PEDIATRICA, IRCCS ISTITUTO DELLE SCIENZE NEUROLOGICHE DI BOLOGNA, ITALY. 3DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE (DIMEC), UNIVERSITÀ DI BOLOGNA, ITALY)

Modalità

Poster Session

Abstract

“The DYNC1H1 gene encodes the cytoplasmic dynein 1 heavy chain, a large component of the multisubunit dynein motor complex that mediates retrograde axonal transport and other intracellular process. An increasing number of phenotype expansions have shown an overlapping phenotype link between motor neuropathies and brain malformations.
We present a 17-year-old girl with neuromuscular involvement and cortical malformation due to a de novo new mutation in the DYNC1H1 gene (c.3188T>C-p.Met1063Thr). Her medical history includes congenital bilateral clubfoot, delayed motor milestones, ADHD and mild intellectual disability. At the age of 7, neurological examination revealed thigh hypotrophy, proximal and distal lower limb weakness, hip and ankle contractures, positive Gower’s sign and lumbar hyperlordosis. CK levels were mildly increased (327 U/L). Electromyography study of the vastus lateralis failed to show clear neurogenic involvement; NCV in the lower limb were normal. Muscle MRI showed fibroadipose replacement in the anterior thigh’s muscles. Vastus lateralis biopsy showed a complete fat replacement; biceps brachii biopsy documented mild fibers size variation and altered distribution of oxidative activity. Array-CGH and NGS panel for myopathies yielded no significant findings. At 17 years, she experienced a convulsive episode followed by recurrent temporal seizures with auditory aura and dysphasia. Interictal EEG showed rare left centro-temporal abnormalities. Brain MRI revealed left hippocampal malrotation and bilateral insular polymicrogyria. Subsequent WES revealed the pathogenic mutation in the DYNC1H1 gene. Our case provides further evidence that patients with DYNC1H1-mutations may experience neuromuscular congenital disorder and structural late onset epilepsy. We discuss the genotype-phenotype correlation in this new mutation.”