Neoplasia in Cri du Chat Syndrome from Italian and German Databases

Abstract

Cri du Chat syndrome (CdC) is a chromosomal abnormality (deletion of short arm of chromosome 5) associated with intellectual disability and typical anatomical abnormalities. Research up to now focuses on the management of the disease during childhood. The longer lifespan of these patients warrants deeper investigations of how and if aging could be affected by the syndrome. We decided to focus on the association of the disease with proliferative disorders. Data on proliferative disorders in a cohort of 321 patients from Italian and German Cri du Chat databases were collected. A neoplasia was present in four patients (age 10–50 yrs), and a fifth patient developed a cholesteatoma during childhood. It is of interest that two cases had an early onset of the neoplasia as compared to the expected age of development in the general population. The chromosome region deleted in 5p does not contain genes whose haploinsufficiency is a well-known main cause of the proliferative disorders observed. We nonetheless believe that reporting even sporadic cases of proliferative disorders in CdC patients may increase our knowledge as to the natural history of the disease. In conclusion, available information suggests that surveillance for cancer development in CdC can follow the guidelines for the general population.

Assessing cancer in people with profound and multiple disabilities

“…In these situations, the risk of cancer overall may be increased or reduced compared to the general population, and the distribution of tumor types (tumor profile) may differ. Examples of such conditions include the conditions trisomy 13, 18, and 21 [ 31 – 33 ], Costello syndrome [ 34 ], Cornelia de Lange syndrome [ 35 ], Rett syndrome [ 36 ], and endocrine and metabolic pathologies [ 22 , 37 ]. Some genetic conditions can also promote early-onset (e.g., childhood) cancers [ 30 ].…”

CNVs affecting cancer predisposing genes (CPGs) detected as incidental findings in routine germline diagnostic chromosomal microarray (CMA) testing

“…Intragenic SDHA inactivating mutations may be associated with phaeochromocytoma, paraganglioma and gastrointestinal stromal tumours 15 39. Although the penetrance of familial SDHA mutations has been estimated at ~40% by age 40 years,40 other evidence suggests that the penetrance is much lower39 and to date we are not aware of any SDHA-related tumours reported in patients with cri-du-chat 41. Nevertheless, subject to appropriate ethical considerations, it would be of interest to investigate adults with cri-du-chat deletions involving SDHA for subclinical evidence of SDHA -related tumours.…”

Perioperative Care of a Child With Cri Du Chat Syndrome

“…Morbidity and mortality are greatest during the first year of life, with 75% of deaths occurring in the first month and about 90% occurring within the first year due to pneumonia, aspiration, and congenital heart defects [ 3 ]. After one year of age, patients have a high survival rate and life expectancy, with some individuals living into their 50’s and one into their 70’s [ 3 , 7 ]. Reports show that 47-75% of patients with CdCS will undergo a surgical procedure or diagnostic testing/imaging requiring immobilization, sedation or general anesthesia [ 2 ].…”