Dystonia, autoimmune disease and cerebral white matter abnormalities in a patient with 18p deletion

Abstract

Dystonia is a clinically and genetically heterogeneous disorder of movement characterized by involuntary and sustained muscle contractions and rigid postures affecting one or more sites of the body. It can be classified according to the distribution of affected body parts, age of onset and etiology 1 . Up to now, at least 15 different loci (DYT1-DYT15) have been described in this condition 1,2 . Adult-onset idiopathic torsion dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer's cramp) has been associated with the DYT7 locus, located in the short arm of chromosome 18 [1][2][3] . Autoimmune diseases have been considered conditions associated with reactions of the immune system against selfantigens or body systems. They are disorders often associated with severe and chronic morbidity. In spite of recent advances, much of their etiology is still unknown 4 . We describe a rare case of a patient with 18p deletion syndrome presenting focal dystonia, Hashimoto thyroiditis, vitiligo and cerebral white matter abnormalities. CaSeThe patient is a 30 year old white woman, the fourth child of a non-consanguineous couple, without any history of similar cases in the family. The patient was born full-term, with a Cesarean section, after a pregnancy without intercurrences. During her first year of life, she had several episodes of infection (otitis and tonsillitis) as well as constipation where laxative use was needed. At 3 months, she had a convulsive crisis during fever. In relation to her neuropsychomotor development, the mother recalls she supported her own head at 6 months and pronounced her first words at the age of three. The patient was also unable to accompany normal school, failing several grades. After a long period without intercurrences, she began with blepharospasm together with cervical dystonia. She presented telarche at the age of 12 and menarche at 13, and at around 20 she began with menstrual irregularity. The hormonal evaluation conducted later diagnosed hypothyroidism due to Hashimoto thyroiditis.During the physical exam at the age of 30, she presented obesity (weighing 70 kg, between the 90-97 percentiles), short stature (149 cm, under the 3 percentile), brachycephaly, but without microcephalia (head circumference of 53 cm -between the 2-50 percentiles), rounded face, ocular hypertelorism (interpupillary distance higher than the 97 percentile), ptosis, blepharospasm, corneal opacification, hypoplasia of the middle third of the face, broad nasal bridge, high palate, short and broad neck, low posterior hairline, broad thorax and accentuated cervical kyphosis ( Figs 1A and B). She also had dextroconvex thoracic scoliosis, small hands and feet with hyperconvex nails (Figs 1C and D) and achromic spots of different sizes, spread about the body (thorax, dorsum and members), and vitiligo was diagnosed. The face remained in a fixed position, always turned to the right and downwards (Figs 1A and B). Nuclear magnetic resonance of the skull reveal...

Spectrum of Movement Disorders in 18p Deletion Syndrome

“…We have identified 16 patients with 18p‐ syndrome and movement disorders (Table ). Dystonia was present in 15 of 16 patients . Ataxia without any dystonic feature was observed in a single patient.…”

“…Dystonia was present in 15 of 16 patients. [5][6][7][8][9][10][11][12][13][14][15][16] Ataxia without any dystonic feature was observed in a single patient. Dystonia is clearly the most commonly reported movement disorder in patients with 18p-syndrome and can present as focal, segmental, multifocal, or generalized dystonia.…”

“…Therefore, we were not able to assess the presence of cerebral white matter T2-hyperintensities, which have been described in some 18p-syndrome patients. 5,9,10,13 The prevalence of movement disorders in 18p-syndrome is probably underestimated because of the presence of important abnormalities in several organ systems in the majority of patients (e.g., skeletal deformities, severe neurodevelopmental problems, and genitourinary abnormalities). One can assume that the focus of medical care for these patients is therefore not immediately directed to abnormal movements.…”

Patchy white matter hyperintensity in ring chromosome 18 syndrome

“…Heterozygotes, however, are assumed to be asymptomatic, and abnormal neuroimaging has not been reported. Neuroimaging in 18p‐ syndrome indicates some cerebral anomalies including holoprosencephaly, arhinocephaly, and agenesis of the corpus callosum . Previous reports relating to 18p‐ syndrome brain imaging included a 30‐year‐old patient with focal dystonia whose MRI showed asymmetrical multiple T2 hyperintensities in the semi‐oval centers and around the lateral ventricles, similar to the MRI in the present case.…”

The monosomy 18p detected by the amniocentesis: de Grouchy syndrome 1

“…Такође је описана веза између дефицијенције имуноглобулина А (IgA) и делеције кратког крака хромозома 18, тако да код оваквих пацијената постоји тенденција ка настанку аутоимуних болести (аутоимуни тиреоидитис, дијабетес мелитус, перницозна анемија и реуматоидни артритис). Приказано је и пар случајева с присутном дистонијом код пацијената са овим синдромом (12)(13)(14). Забележени су и случајеви пацијената са keratosis pilaris и ulerythema ophryogenes, као и случај пацијента са отвореним duktus arteriosus и стенозом пулмонарне валвуле (15,16).…”