Novel clinical finding in MECP2 duplication syndrome

Abstract

MECP2 duplication syndrome (MECP2 DS) is a newly described genetic condition, with approximately 120 affected males being reported in so far [1–11]. The clinical features of this syndrome are hypotonia with feeding difficulties in the first month of life followed by spasticity in childhood, delayed motor developmental milestones, severe speech delay, dysmorphic features (brachycephaly, midfacial hypoplasia, large ears, and flat nasal bridge), moderate to severe intellectual disability, autistic features, seizures, recurrent respiratory infections, hypoplasia of the corpus callosum, severe constipation, and less frequent bladder dysfunction (urinary retention, bladder dilatation) [8]. Movement disorders (i.e., choreiform movements, stereotypies, and repetitive behaviors—especially, midline hand movements) were reported in various percentages of patients; rocking, spinning, and self-injurious behavior were also reported [11]. Most females heterozygous for MECP2 duplication are asymptomatic, but can exhibit features of the broad autism phenotype or other symptoms like anxiety, depression, and compulsions [11]. These patients’ management is multidisciplinary, including the treatment of feeding difficulties and of respiratory infection, physical therapy, speech therapy, ergotherapy, and specific behavioral therapy. We report on a 6-year-old boy, the first child of healthy nonconsanguineous parents, born after an uneventful pregnancy with a birth weight 2,500 g, Apgar score 10. No movement disorders or attention disorders in the family history were reported. Shortly after birth, the boy presented hypotonia with delayed psychomotor development; he held his head at 10 months, sat at 15 months, walked alone at 36 months, and spoke first words at 40 months. In the first year of life, the patient had feeding difficulties and recurrent respiratory infections. The clinical examination showed: weight 23 kg (Pc 75), height 115 cm (Pc 50), occipitofrontal circumference 48 cm (\2 DS); facial dysmorphism (hypertelorism; partial palpebral ptosis; open, carp-shaped mouth; micrognathia) (Fig. 1); cryptorchidism; bilateral pyramidal syndrome; severe intellectual disability; severe speech delay; autistic features; drooling. A prominent feature of the clinical picture was severe hyperkinesis, manifested as random non-purposeful movements, occurring throughout the day, in any environment (at home, in kindergarten, and in other public spaces), more prominent during the morning and in the afternoon impairing daily activities (the child was not able to play or to stay at the table to do a task for more than 5 min, thus not being able to participate in different activities together with other children). The patient presented also stereotyped movements (hand-flapping movements) and agitation during sleep. Hyperkinesis was, actually, the main reason for referral to our Department. The patient had not chorea, tremor, or epileptic seizures. To our knowledge, this is the first case with confirmed MECP2 duplication and hyperkinesis and the MECP2 duplication syndrome patients being considered rather hypoactive [12]. Biological tests, EEG and cerebral MRI were normal. M. Budisteanu, S. M. Papuc and A. Arghir equally contributed to this paper.