A de novo 0.63 Mb 6q25.1 deletion associated with growth failure, congenital heart defect, underdeveloped cerebellar vermis, abnormal cutaneous elasticity and joint laxity.
Deletions of the long arm of chromosome 6 are rare and are characterized by great clinical variability according to the deletion breakpoint. We report a on 6-year-old girl with a de novo 0.63 Mb deletion on chromosome 6q25.1 who demonstrated multiple congenital anomalies including a ventricular septal defect and an underdeveloped cerebellar vermis. She presented with severe pre- and post-natal growth failure, hyperextensible small joints (Beighton scores = 8/9; with normal parental scores), and an abnormally elastic, redundant skin. Abnormally high upper/lower segment ratio (i.e., 1.34 = > 3SD), mild dysmorphic facial features and developmental delay were also present. The girl's phenotype was compared with: (i) two girls, each previously reported by Bisgaard et al. and Caselli et al. with similar albeit larger (2.6-7.21 Mb) deletions; (ii) seven additional individuals (6 M; 1 F) harboring deletions within the 6q25.1 region reported in the literature; and (iii) ten further patients (5 M; 4 F; 1 unrecorded sex) recorded in the DECIPHER 6.0 database. We reported on the present girl as her findings could contribute to advance the phenotype of 6q deletions. In addition, the present deletion is the smallest so far recorded in the 6q25 region encompassing eight known genes [vs. 41 of Bisgaard et al., and 23 of Caselli et al.,], including the TAB2 (likely responsible for the girl's congenital heart defect), LATS1 gene, and the UST gene (a regulator of the homeostasis of proteoglycans, which could have played a role in the abnormal dermal and cartilage elasticity).
Department of Paediatric Neurology, Chelsea and Westminster Hospital, London, United Kingdom.|Unit of Genetics and Paediatric Immunology, Department of Paediatrics, University of Messina, Messina, Italy.
Vincenzo
V
Salpietro
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Martino
M
Ruggieri
Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Kshitij
K
Mankad
Unit of Infantile Neuropsychiatry, Department of Paediatrics, University of Messina, Messina, Italy.
Gabriella
G
Di Rosa
Unit of Neuroradiology, Department of Biomedical Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy.
Francesca
F
Granata
Unit of Genetics and Paediatric Immunology, Department of Paediatrics, University of Messina, Messina, Italy.
Italia
I
Loddo
Unit of Genetics and Paediatric Immunology, Department of Paediatrics, University of Messina, Messina, Italy.
Emanuela
E
Moschella
Unit of Pediatric Cardiology, Department of Paediatrics, University of Messina, Messina, Italy.
Maria Pia
MP
Calabro
Institute of Medical Genetics, "CSS-Mendel" Institute, Rome, Italy.
Anna
A
Capalbo
Institute of Medical Genetics, "CSS-Mendel" Institute, Rome, Italy.
Laura
L
Bernardini
Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Antonio
A
Novelli
Institute of Neurological Sciences, National Research Council, Catania, Italy.|National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.
Agata
A
Polizzi
Institute for Physiological Chemistry and Pathobiochemistry, University of Munster, Munster, Germany.
Daniela G
DG
Seidler
Unit of Genetics and Paediatric Immunology, Department of Paediatrics, University of Messina, Messina, Italy.
Teresa
T
Arrigo
Unit of Genetics and Paediatric Immunology, Department of Paediatrics, University of Messina, Messina, Italy.
Silvana
S
Briuglia
D000015:Abnormalities, Multiple / Q000235:genetics*; D065814:Cerebellar Vermis / Q000002:abnormalities*; D002648:Child; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D004548:Elasticity / Q000502:physiology; D005260:Female; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007593:Joint Instability / Q000235:genetics*
6q deletion; 6q25 syndrome; Ehlers-Danlos syndrome; IUGR; LATS1; TAB2; UST; arrhythmia; cerebellar hypoplasia; congenital heart defect; growth retardation