Programmpunkt

12:08–12:10

Titel: 9p Deletion 9p24.3p23 in an 8-year old Girl with Developmental Delay, a large Head Circumference and Brachydactyly
ID: P-ClinG-104
Art: Postertalk
Redezeit: 2 min
Session: Poster Session
ClinG 1

Referent: Louiza Toutouna (Freiburg/DE)


Abstract - Text

Abstract-Text

Introduction:


Deletions in the distal short arm of chromosome 9 are rare. To date over 140 individuals with 9p deletions habe been described, carrying either an isolated deletion or an unbalanced translocation involving 9p and another chromosome. Clinical features include developmental delay, trigonocephaly, short palpebral fissures, a long philtrum, flat nasal bridge with anteverted nares, ear anomalies with low-set malformed ears and micro-/retrognathia. Other features include hypotonia, widely spaced nipples, male to female sex reversal and rarely finger anomalies such as dolichomesophalangy and clino-/brachydactyly, heart defects, omphalocele and teeth/skeletal anomalies. Various studies have attempted to elucidate a genotype-phenotype correlation as well as a critical region for trigonocephaly with inconclusive results. Developmental delay is a universal characteristic of 9p deletions and is independent of the exact region and location of the deletion.



Clinical report:


Here we report an 8-year old girl with developmental delay affecting language and psychomotor development since infancy. Epileptic seizures manifested in the first 15 months. She walked with over 2.5 years. Speech development was also delayed with sentence building starting in nursery school. Physical exam revealed mild facial dysmorphic features, widely spaced nipples as well as brachydactyly of the 4th and 5th fingers and more pronouncedly of the 3rd -5th toes with sandal gap. Her body measurements at age 7 9/12 were weight at 85th centile, length at 85th centile and head circumference at 92nd centile.



Methods and Results:


Chromosome analysis revealed a distal interstitial deletion involving bands 9p24.3p23: 46,XX,del(9)(p24.3p23). The microarray analysis defined a 12.13Mb deletion including 98 genes and setting the breakpoints at positions chr9:2025657_14155895 (GRCh37) interrupting SMARCA2, associated with Nicolaides-Baraitser syndrome, at the distal end and NFIB, haploinsufficiency of which is associated with intellectual disability and macrocephaly, at the proximal end. FISH analyses with the probe RP11-1142H1 (Empire Genomics) binding in 9p24.3 (pos. 2362216-2567823) in the patient and both parents confirmed a de novo deletion. Whole exome sequencing (WES) showed no additional pathogenic variants.



Conclusions:


Numerous patients with a distal deletion in 9p have been described, presenting with a variety of clinical manifestations. Here we report a girl with a de novo deletion of 12.13Mb involving 9p24.3p23.  None of the listed patients in DECIPHER nor in the literature shares the identical deletion breakpoints with our patient. Interestingly she lacked the typical trigonocephaly but demonstrated a large head circumference and mild dysmorphic features as well as pronounced brachydactyly of the toes. This case contributes to the delineation of the phenotypic spectrum of 9p deletions.