A familiar case of ptosis and dysphagia with facial dysmofisms due to a novel KMT2D gene mutation.

Francesca Cortese

A familiar case of ptosis and dysphagia with facial dysmofisms due to a novel KMT2D gene mutation.

Autori

FRANCESCA CORTESE (NEUROMUSCULAR AND RARE NEUROLOGICAL DISEASES CENTER, NEUROLOGY UNIT, SAN FILIPPO NERI HOSPITAL, ASLROMA 1, ROME – NEUROLOGY)
MARIANNA BRIENZA (NEUROMUSCOLAR AND RARE NEUROLOGICAL DISEASES CENTER, NEUROLOGY UNIT, SAN FILIPPO NERI HOSPITAL, ASL ROMA 1, ROME – NEUROLOGY)
LAURA DE GIGLIO (NEUROMUSCOLAR AND RARE NEUROLOGICAL DISEASES CENTER, NEUROLOGY UNIT, SAN FILIPPO NERI HOSPITAL, ASL ROMA 1, ROME – NEUROLOGY)
ROSALBA CARROZZO (UNIT OF CELL BIOLOGY AND DIAGNOSIS OF MITOCHONDRIAL DISORDERS, LABORATORY OF MEDICAL GENETICS, BAMBINO GESÙ CHILDREN’S HOSPITAL IRCCS, ROME – BIOLOGY-MITOCHONDRIAL DISEASES)
ALESSANDRA TORRACO (UNIT OF CELL BIOLOGY AND DIAGNOSIS OF MITOCHONDRIAL DISORDERS, LABORATORY OF MEDICAL GENETICS, BAMBINO GESÙ CHILDREN’S HOSPITAL IRCCS, ROME – BIOLOGY-MITOCHONDRIAL DISEASES)
FABIANA FATTORI (LABORATORY OF MEDICAL GENETICS, TRANSLATIONAL CYTOGENOMICS RESEARCH UNIT, BAMBINO GESÙ CHILDREN HOSPITAL IRCCS, ROME – BIOLOGY-NEUROMUSCOLAR DISEASES)
LUCA BOSCO (NEUROMUSCULAR DISORDERS RESEARCH UNIT, BAMBINO GESÙ CHILDREN’S HOSPITAL IRCCS, ROME – BIOLOGY-NEUROMUSCOLAR DISEASES)
MARIA CONCETTA ALTAVISTA (RARE NEUROLOGICAL DISESES CENTER, NEUROLOGY UNIT, SAN FILIPPO NERI HOSPITAL, ASL ROMA 1, ROME – NEUROLOGY)
ELENA MARIA PENNISI (NEUROMUSCOLAR AND RARE NEUROLOGICAL DISEASES CENTER, NEUROLOGY UNIT, SAN FILIPPO NERI HOSPITAL, ASL ROMA 1, ROME – NEUROLOGY)

Presentatore

FRANCESCA CORTESE (NEUROMUSCULAR AND RARE NEUROLOGICAL DISEASES CENTER, NEUROLOGY UNIT, SAN FILIPPO NERI HOSPITAL, ASLROMA1, ROME)

Modalità

Poster Session

Abstract

“We report the case of a 70-year-old woman who presented in our outpatients department complaining blepharoptosis and mild dysphagia for more than 20 years. She underwent surgical correction for ptosis several times.
On neurological examination she showed a moderate ptosis, mild dysphagia, facial muscles weakness, lower limbs proximal muscles weakness with difficulties to arise from seated position. No fatigability or myotonia were found on clinical and neurophysiological examination.
Mild dysmorphic features were also observed, including broad and sparse eyebrows, large cupped ears and persistent fingertip pads. The patient reported similar dysmorphic features and weakness in her mother and maternal aunt. Pneumological examination showed a mild reduction of MIP and MEP with mild restriction.
Congenital myasthenic syndromes, oculopharyngeal dystrophy, myotonic dystrophy and mitochondrial disease were ruled out using genetic testing.
Exome sequencing detected a novel heterozygous mutation in KMT2D gene (c.16433C>A / p.Ala5478Asp).
Heterozygous pathogenic mutation in this gene can cause Kabuki syndrome, a rare (1:35000) syndrome characterized by typical dysmorphic features, psychomotor developmental delay, hypotonia in infants and other systemic manifestations. Typical dysmorphic features include arched and broad eyebrows, long palpebral fissures, ptosis, large and cupped ears and persistent fingerpads.
Our patient showed only mild facial and proximal weakness with facial dysmorphism. It is conceivable that different variants of the same gene can alter distinct protein domains, resulting in different clinical phenotypes.
This case contributes broading the spectrum of Kabuki syndrome, suggesting that this diagnosis be sought in patients with eyelid ptosis and dysphagia associated with slight facial dysmorphic traits.”