18p deletion (18p-) syndrome is a rare chromosome abnormality that has a wide range of phenotypes, with short stature, intellectual disability, and facial dysmorphism being the main clinical features. Here, we report the first case in Korea of a 16-year-old male adolescent with 18p- syndrome resulting from de novo unbalanced whole-arm translocation between chromosomes 13 and 18 (45, XY, der(13;18)(q10:q10)). Three rare clinical findings were discovered that had not been reported in the previous literature; morbid obesity without other hormonal disturbances, rib cage deformity leading to the direct compression of the liver, and lumbar spondylolisthesis at the L5-S1 level. This case expands the phenotypic spectrum of 18p- syndrome and highlights the importance of considering chromosomal analysis, since this syndrome can be easily overlooked in a clinical setting, especially without distinctive symptoms of other organs, due to its nonspecific but typical features of short stature and mild intellectual disability with a mildly dysmorphic face. Moreover, since not all cases of 18p- syndrome with unbalanced translocation (13;18) show the same phenotype, multidisciplinary examinations and follow-up seem to be important to monitor evolving and developing clinical manifestations and to predict prognosis in advance associated with the specific genes of 18p breakpoint regions.

We report the association, not previously described, between trisomy 20/monosomy 18 and congenital bilateral perisylvian syndrome (CBPS), a condition featuring intellectual disability, epilepsy, oro-motor dysfunction and bilateral perisylvian polymicrogyria (BPP) in a 29-year-old individual. Detailed clinical evaluation, long-term EEG and EEG analysis by means of electrical source imaging (ESI), 3T MRI and array-CGH were performed. Clinical examination showed moderate/severe intellectual disability, dysmorphic features, oro-motor dysfunction, short stature, abnormal hands and feet, bradykinesia and abnormal posture. The patient had suffered from drug-resistant epilepsy since infancy. Brain MRI showed that BPP was consistent with CBPS. Additional imaging features revealed corpus callosum and cerebellar hypoplasia and fusion of the C1-C2 vertebrae. Ictal EEG and ESI documented tonic seizures originating from the right polymicrogyric cortex. Facial gestalt included dysmorphic features reported in patients with 18- and 20+ chromosomal rearrangements. Array-CGH showed an unbalanced translocation, arr(18p)x1(20p)x3. In conclusion, we provide a detailed electro-clinical and MRI description of a novel condition characterized by the association between trisomy 20p/monosomy 18p and CBPS, also illustrating its clinical evolution into adulthood. This information may help paediatricians, neurologists and geneticists to better counsel families about the developmental prognosis of this rare unbalanced chromosomal rearrangement.

UNASSIGNED: Deletion of the short arm of chromosome 18 leads to 18p deletion syndrome. Clinical features include short stature, facial dysmorphism, mental retardation, and several types of movement disorders.
UNASSIGNED: The 18p deletion syndrome in our patient was diagnosed using karyotype analysis and confirmed by genome-wide single-nucleotide polymorphism array. We have performed a literature search and summarized all previously reported patients with 18p deletion syndrome and movement disorders.
UNASSIGNED: We present a 41-year-old male patient with childhood-onset generalized dystonia. Dystonia is the most prevalent movement disorder in 18p deletion patients, with onset ranging from childhood to adulthood. Chorea, myoclonus, tremor, tics, and ataxia have been reported in a minority of these patients.
UNASSIGNED: Dystonia is commonly observed in 18p deletion syndrome. The variable size of the deletion on 18p is probably responsible for the broad phenotypic variability of movement disorders in this syndrome.

Since 18p- was first described in 1963, much progress has been made in our understanding of this classic deletion condition. We have been able to establish a fairly complete picture of the phenotype when the deletion breakpoint occurs at the centromere, and we are working to establish the phenotypic effects when each gene on 18p is hemizygous. Our aim is to provide genotype-specific anticipatory guidance and recommendations to families with an 18p- diagnosis. In addition, establishing the molecular underpinnings of the condition will potentially suggest targets for molecular treatments. Thus, the next step is to establish the precise effects of specific gene deletions. As we look forward to deepening our understanding of 18p-, our focus will continue to be on the establishment of robust genotype-phenotype correlations and the penetrance of these phenotypes. We will continue to follow our 18p- cohort closely as they age to determine the presence or absence of some of these diagnoses, including spinocerebellar ataxia (SCA), facioscapulohumeral muscular dystrophy (FSHD), and dystonia. We will also continue to refine the critical regions for other phenotypes as we enroll additional (hopefully informative) participants into the research study and as the mechanisms of the genes in these regions are elucidated. Mouse models will also be developed to further our understanding of the effects of hemizygosity as well as to serve as models for treatment development.

We report a monosomy 18p syndrome in a male patient with polyglandular autoimmune syndrome (PAS) type IIIA. A 34-year-old mentally retarded diabetic male patient with short stature, wide earlaps, old-looking face, straight nasal bone, atrophic mouth, drooping cheeks, full teeth loss, and soft, weak and sparse white hair was admitted to the outpatient endocrinology clinic. Chromosome analysis of the patient revealed 46,XY,del(18)(p11.2). He was also diagnosed with autoimmune thyroiditis, primary hypothyroidism and diabetes mellitus type 1. We concluded that monosomy 18p syndrome may be associated with autoimmune diseases and if this is suspected, patients should be examined for an endocrine deficiency.

We applied CMA to detect chromosomal variations during a prenatal diagnosis and detected a 4.5Mb pure microdeletion at 18p11.3 that was not detected by conventional karyotyping. Fluorescent in situ hybridization (FISH) analysis was performed to confirm the deletion. Accurate breakpoints of the deletion in this patient were used to build correlations between monosomy 18p and the concomitant phenotypes, particularly holoprosencephaly (HPE), which is rarely reported in monosomy 18p11.3.