Whole arm deletions of 18p: Medical and developmental effects

Abstract

Deletions of the short arm of chromosome 18 have been well-described in case reports. However, the utility of these descriptions in clinical practice is limited by varied and imprecise breakpoints. As we work to establish genotype-phenotype correlations for 18p-, it is critical to have accurate and complete clinical descriptions of individuals with differing breakpoints. In addition, the developmental profile of 18p- has not been well-delineated. We undertook a thorough review of the medical histories of 31 individuals with 18p- and a breakpoint in the centromeric region. We collected developmental data using mailed surveys and questionnaires. The most common findings included neonatal complications; cardiac anomalies; hypotonia; MRI abnormalities; endocrine dysfunction; strabismus; ptosis; and refractive errors. Less common features included holoprosencephaly and its microforms; hearing loss; and orthopedic anomalies. The developmental effects of the deletion appear to be less severe than reported in the literature, as average IQ scores were in the range of borderline intellectual functioning. Based on responses to standardized questionnaires, it appears this population has marked difficulty with activities of daily living, though several young adults were able to live independent of their parents. This manuscript represents the most comprehensive description of a cohort of 18p- individuals with identical breakpoints. Despite identical breakpoints, a great deal of phenotype variability remained among this population, suggesting that many of the genes on 18p- cause low-penetrance phenotypes when present in a hemizygous state. Future efforts will focus on the clinical description of individuals with more distal breakpoints and the identification of critical regions and candidate genes.

Anterior Pituitary Aplasia in an Infant with Ring Chromosome 18p Deletion

“…Reports have varied on the developmental and behavioral manifestations, although recent reviews estimate an average IQ of 69, with patients ranging from mild impairment to normal functioning [2]. However regardless of IQ, many studies have noted that these individuals have difficulty with communication skills, activities of daily living, and management of social and occupational activities [2, 10]. …”

“…Of the case reports describing GH deficiency associated with isolated 18p deletion syndrome, 2 of 3 patients had normal brain MRI [10, 11]. The third case report presented a patient with only partial GH deficiency and empty sella with rudimentary pituitary stalk [12].…”

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome

“…To date, there have been about 150 cases reported worldwide. Since most clinical characteristics are nonspecific in 18p deletion patients, cytogenetic analysis is considered a main evidence for diagnosis [Hasi-Zogaj et al, 2015;Sebold et al, 2015]. With the development of molecular genetics, a clear definition of precise deletion breakpoints and specific deleted genes in the syndrome has been achieved using microarray technology [Hasi-Zogaj et al, 2015].…”

Síndrome por deleción 18p diagnosticado por hibridación genómica comparada. Presentación de un caso con fenotipo leve

“…A pesar de encontrarse puntos de deleción idénticos, una gran cantidad de variabilidad fenotípica se mantiene en diferentes estudios, lo que sugiere que muchos de los genes involucrados en el brazo corto del cromosoma 18 causan fenotipos de baja penetrancia cuando están presentes en un estado hemicigoto, como se puede apreciar en la descripción de los casos reportados por el grupo de Schaub en 1982, de Hadedank en 1983, de Sebold y el de Hasi-Zogaj en 2015. 6,11,12 La relación entre mujeres y hombres es de 3 a 2, en ellas se ha reportado disgenesia gonadal, trastornos menstruales y de fertilidad. 2 El diagnóstico prenatal de este síndrome es posible realizarlo por amniocentesis y debe considerarse en los casos de holoprosencefalia.…”