PMID- 30847392
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 2378-8038 (Print)
IS  - 2378-8038 (Electronic)
IS  - 2378-8038 (Linking)
VI  - 4
IP  - 1
DP  - 2019 Feb
TI  - Clinical application of molecular genetics in lymphatic malformations.
PG  - 170-173
LID - 10.1002/lio2.241 [doi]
AB  - OBJECTIVES: To describe the clinical presentation of lymphatic malformations (LM) 
      and genotypically associated disorders and to summarize the recent literature 
      regarding the genetic etiology of LM and provide a biologic correlation to 
      medical and surgical management. RESULTS: LM are congenital lesions derived from 
      a developmental abnormality of the lymphatic vessels. The severity of disease 
      varies widely and complications can occur with higher staged disease and those 
      associated with a known constellation of symptoms. Somatic mutations of the 
      PIK3CA gene have been found to be an etiologic factor in the development of LM 
      and associated overgrowth syndromes. Sirolimus is a mammalian target of rapamycin 
      (mTOR) inhibitor that inhibits the pathway downstream of PIK3CA. Preliminary 
      studies in select groups of patients suggest that sirolimus has a role in the 
      medical management of certain aspects of this disease. CONCLUSIONS: Discovery of 
      LM molecular genetics has led to the possibility of targeted therapies and 
      highlights the importance of precision medicine in rare diseases. Identifying 
      genetic mutations in larger cohorts of patients with LM will lead to additional 
      insights. Knowledge of the genetic basis for disease can then lead to discovery 
      of directed medical therapy. A specific molecular diagnosis can also help 
      families understand better why their child is different and provide accurate 
      counseling for subsequent pregnancies. LEVEL OF EVIDENCE: 6.
FAU - Padia, Reema
AU  - Padia R
AUID- ORCID: 0000-0002-5876-7816
AD  - Division of Pediatric Otolaryngology Seattle Children's Hospital Seattle 
      Washington.
FAU - Zenner, Kaitlyn
AU  - Zenner K
AD  - Department of Otolaryngology-Head and Neck Surgery, Division of Genetic Medicine 
      University of Washington School of Medicine Seattle Washington.
FAU - Bly, Randall
AU  - Bly R
AD  - Division of Pediatric Otolaryngology Seattle Children's Hospital Seattle 
      Washington.
AD  - Department of Otolaryngology-Head and Neck Surgery, Division of Genetic Medicine 
      University of Washington School of Medicine Seattle Washington.
FAU - Bennett, James
AU  - Bennett J
AD  - Department of Surgery, and the Center for Developmental Biology and Regenerative 
      Medicine Seattle Children's Hospital Seattle Washington.
AD  - Department of Pediatrics Division of Genetic Medicine, University of Washington 
      School of Medicine Seattle Washington.
FAU - Bull, Catherine
AU  - Bull C
AD  - Division of Pediatric Otolaryngology Seattle Children's Hospital Seattle 
      Washington.
FAU - Perkins, Jonathan
AU  - Perkins J
AUID- ORCID: 0000-0003-0181-3997
AD  - Division of Pediatric Otolaryngology Seattle Children's Hospital Seattle 
      Washington.
AD  - Department of Otolaryngology-Head and Neck Surgery, Division of Genetic Medicine 
      University of Washington School of Medicine Seattle Washington.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190112
PL  - United States
TA  - Laryngoscope Investig Otolaryngol
JT  - Laryngoscope investigative otolaryngology
JID - 101684963
PMC - PMC6383318
OTO - NOTNLM
OT  - Lymphatic malformation
OT  - activating mutation
OT  - bone
OT  - genetics
OT  - lymphocytopenia
OT  - molecular genetics
OT  - overgrowth syndrome
OT  - sirolimus
OT  - somatic mutation
EDAT- 2019/03/09 06:00
MHDA- 2019/03/09 06:01
PMCR- 2019/01/12
CRDT- 2019/03/09 06:00
PHST- 2018/07/23 00:00 [received]
PHST- 2018/10/12 00:00 [revised]
PHST- 2018/11/08 00:00 [accepted]
PHST- 2019/03/09 06:00 [entrez]
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2019/03/09 06:01 [medline]
PHST- 2019/01/12 00:00 [pmc-release]
AID - LIO2241 [pii]
AID - 10.1002/lio2.241 [doi]
PST - epublish
SO  - Laryngoscope Investig Otolaryngol. 2019 Jan 12;4(1):170-173. doi: 
      10.1002/lio2.241. eCollection 2019 Feb.