Cornelia de Lange syndrome with NIPBL mutation and mosaic Turner syndrome in the same individual.
BACKGROUND
Cornelia de Lange syndrome (CdLS) is a dominantly inherited disorder characterized by facial dysmorphism, growth and cognitive impairment, limb malformations and multiple organ involvement. Mutations in NIPBL gene account for about 60% of patients with CdLS. This gene encodes a key regulator of the Cohesin complex, which controls sister chromatid segregation during both mitosis and meiosis. Turner syndrome (TS) results from the partial or complete absence of one of the X chromosomes, usually associated with congenital lymphedema, short stature, and gonadal dysgenesis.


METHODS
Here we report a four-year-old female with CdLS due to a frameshift mutation in the NIPBL gene (c.1445_1448delGAGA), who also had a tissue-specific mosaic 45,X/46,XX karyotype. The patient showed a severe form of CdLS with craniofacial dysmorphism, pre- and post-natal growth delay, cardiovascular abnormalities, hirsutism and severe psychomotor retardation with behavioural problems. She also presented with minor clinical features consistent with TS, including peripheral lymphedema and webbed neck. The NIPBL mutation was present in the two tissues analysed from different embryonic origins (peripheral blood lymphocytes and oral mucosa epithelial cells). However, the percentage of cells with monosomy X was low and variable in tissues. These findings indicate that, ontogenically, the NIPBL mutation may have appeared before the mosaic monosomy X.


CONCLUSIONS
The coexistence in several patients of these two rare disorders raises the issue of whether there is indeed a cause-effect association. The detailed clinical descriptions indicate predominant CdLS phenotype, although additional TS manifestations may appear in adolescence.
Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University of Gdańsk, Poland.
Jolanta
J
Wierzba
María Concepción
MC
Gil-Rodríguez
Anna
A
Polucha
Beatriz
B
Puisac
María
M
Arnedo
María Esperanza
ME
Teresa-Rodrigo
Dorota
D
Winnicka
Fausto G
FG
Hegardt
Feliciano J
FJ
Ramos
Janusz
J
Limon
Juan
J
Pié
D018797:Cell Cycle Proteins; D002648:Child; D003635:De Lange Syndrome / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008214:Lymphocytes; D009030:Mosaicism; D009061:Mouth Mucosa; D011506:Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D014424:Turner Syndrome / Q000235:genetics*
D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins