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Thoracolumbar scoliosis

MedGen UID:
196671
Concept ID:
C0749379
Anatomical Abnormality
Synonym: Scoliosis, thoracolumbar
 
HPO: HP:0002944

Term Hierarchy

Conditions with this feature

Langer-Giedion syndrome
MedGen UID:
6009
Concept ID:
C0023003
Disease or Syndrome
Trichorhinophalangeal syndrome (TRPS) comprises TRPS I (caused by a heterozygous pathogenic variant in TRPS1) and TRPS II (caused by contiguous gene deletion of TRPS1, RAD21, and EXT1). Both types of TRPS are characterized by distinctive facial features; ectodermal features (fine, sparse, depigmented, and slow growing hair; dystrophic nails; and small breasts); and skeletal findings (short stature; short feet; brachydactyly with ulnar or radial deviation of the fingers; and early, marked hip dysplasia). TRPS II is characterized by multiple osteochondromas (typically first observed clinically on the scapulae and around the elbows and knees between ages 1 month and 6 years) and an increased risk of mild-to-moderate intellectual disability.
Gordon syndrome
MedGen UID:
66314
Concept ID:
C0220666
Disease or Syndrome
DA3, or Gordon syndrome, is distinguished from other distal arthrogryposes by short stature and cleft palate (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA3 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 5 (DA5; 108145) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of ocular abnormalities and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders may represent variable expressivity of the same condition. For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Autosomal recessive multiple pterygium syndrome
MedGen UID:
82696
Concept ID:
C0265261
Congenital Abnormality
Multiple pterygium syndromes comprise a group of multiple congenital anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis) (Morgan et al., 2006). The multiple pterygium syndromes are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal (253290) and nonlethal (Escobar) types.
Cholestasis-pigmentary retinopathy-cleft palate syndrome
MedGen UID:
208652
Concept ID:
C0795969
Disease or Syndrome
MED12-related disorders include the phenotypes of FG syndrome type 1 (FGS1), Lujan syndrome (LS), X-linked Ohdo syndrome (XLOS), Hardikar syndrome (HS), and nonspecific intellectual disability (NSID). FGS1 and LS share the clinical findings of cognitive impairment, hypotonia, and abnormalities of the corpus callosum. FGS1 is further characterized by absolute or relative macrocephaly, tall forehead, downslanted palpebral fissures, small and simple ears, constipation and/or anal anomalies, broad thumbs and halluces, and characteristic behavior. LS is further characterized by large head, tall thin body habitus, long thin face, prominent nasal bridge, high narrow palate, and short philtrum. Carrier females in families with FGS1 and LS are typically unaffected. XLOS is characterized by intellectual disability, blepharophimosis, and facial coarsening. HS has been described in females with cleft lip and/or cleft palate, biliary and liver anomalies, intestinal malrotation, pigmentary retinopathy, and coarctation of the aorta. Developmental and cognitive concerns have not been reported in females with HS. Pathogenic variants in MED12 have been reported in an increasing number of males and females with NSID, with affected individuals often having clinical features identified in other MED12-related disorders.
Spondylometaphyseal dysplasia, Golden type
MedGen UID:
208672
Concept ID:
C0796172
Disease or Syndrome
A rare primary bone dysplasia disorder with characteristics of severe short stature, coarse facies, thoracolumbar kyphoscoliosis and enlarged joints with contractures. Psychomotor delay and intellectual disability may also be associated. Radiographic features include flat vertebral bodies, lacy ossification of the metaphyses of long bones and iliac crests, and marked sclerosis of the skull base.
Cervical ribs, Sprengel anomaly, anal atresia, and urethral obstruction
MedGen UID:
318617
Concept ID:
C1832391
Disease or Syndrome
Spinal dysplasia, Anhalt type
MedGen UID:
318632
Concept ID:
C1832464
Disease or Syndrome
Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome
MedGen UID:
335185
Concept ID:
C1845446
Disease or Syndrome
Corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome is a developmental anomalies syndrome characterized by coloboma of the iris and optic nerve, facial dysmorphism (high forehead, microretrognathia, low-set ears), intellectual deficit, agenesis of the corpus callosum (ACC), sensorineural hearing loss, skeletal anomalies and short stature.
Myosclerosis
MedGen UID:
338098
Concept ID:
C1850671
Disease or Syndrome
Collagen VI-related dystrophies (COL6-RDs) represent a continuum of overlapping clinical phenotypes with Bethlem muscular dystrophy at the milder end, Ullrich congenital muscular dystrophy (UCMD) at the more severe end, and a phenotype in between UCMD and Bethlem muscular dystrophy, referred to as intermediate COL6-RD. Bethlem muscular dystrophy is characterized by a combination of proximal muscle weakness and joint contractures. Hypotonia and delayed motor milestones occur in early childhood; mild hypotonia and weakness may be present congenitally. By adulthood, there is evidence of proximal weakness and contractures of the elbows, Achilles tendons, and long finger flexors. The progression of weakness is slow, and more than two thirds of affected individuals older than age 50 years remain independently ambulatory indoors, while relying on supportive means for mobility outdoors. Respiratory involvement is not a consistent feature. UCMD is characterized by congenital weakness, hypotonia, proximal joint contractures, and striking hyperlaxity of distal joints. Decreased fetal movements are frequently reported. Some affected children acquire the ability to walk independently; however, progression of the disease results in a loss of ambulation by age ten to eleven years. Early and severe respiratory insufficiency occurs in all individuals, resulting in the need for nocturnal noninvasive ventilation (NIV) in the form of bilevel positive airway pressure (BiPAP) by age 11 years. Intermediate COL6-RD is characterized by independent ambulation past age 11 years and respiratory insufficiency that is later in onset than in UCMD and results in the need for NIV in the form of BiPAP by the late teens to early 20s. In contrast to individuals with Bethlem muscular dystrophy, those with intermediate COL6-RD typically do not achieve the ability to run, jump, or climb stairs without use of a railing.
Cold-induced sweating syndrome 2
MedGen UID:
342816
Concept ID:
C1853198
Disease or Syndrome
Cold-induced sweating syndrome (CISS) and its infantile presentation, Crisponi syndrome(CS) is characterized by dysmorphic features (distinctive facies, lower facial weakness, flexion deformity at the elbows, camptodactyly with fisted hands, misshapen feet, and overriding toes); intermittent contracture of facial and oropharyngeal muscles when crying or being handled with puckering of lips and drooling of foamy saliva often associated with laryngospasm and respiratory distress; excessive startling and opisthotonus-like posturing with unexpected tactile or auditory stimuli; poor suck reflex and severely impaired swallowing; and a scaly erythematous rash. During the first decade of life, children with CISS/CS develop profuse sweating of the face, arms, and chest with ambient temperatures below 18º to 22º C, and with other stimuli including nervousness or ingestion of sweets. Affected individuals sweat very little in hot environments and may feel overheated. Progressive thoracolumbar kyphoscoliosis occurs, requiring intervention in the second decade.
Neonatal diabetes mellitus with congenital hypothyroidism
MedGen UID:
347541
Concept ID:
C1857775
Disease or Syndrome
Neonatal diabetes mellitus with congenital hypothyroidism (NDH) syndrome is characterized by intrauterine growth retardation and onset of nonimmune diabetes mellitus within the first few weeks of life. Other features include renal parenchymal disease, primarily renal cystic dysplasia, and hepatic disease, with hepatitis in some patients and hepatic fibrosis and cirrhosis in others. Facial dysmorphism, when present, consistently involves low-set ears, epicanthal folds, flat nasal bridge, long philtrum, and thin upper lip. Most patients exhibit developmental delay (Dimitri et al., 2015).
Brachydactyly type B1
MedGen UID:
349432
Concept ID:
C1862112
Congenital Abnormality
A rare subtype of brachydactyly type B characterized by hypoplasia or aplasia of the distal phalanges of digits 2-5 with or without nail dysplasia, in association with fusion of the middle and distal phalanges, a broad or bifid thumb, and occasionally distal and proximal symphalangism or syndactyly. The feet are less severely affected than the hands.
Camurati-Engelmann disease, type 2
MedGen UID:
419470
Concept ID:
C2931683
Disease or Syndrome
Camurati-Engelmann Disease not associated with TGFB1. This is an n-of-1 use case where only one patient or family has been described with this disorder.
Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome
MedGen UID:
896409
Concept ID:
C4225270
Disease or Syndrome
Kosaki overgrowth syndrome (KOGS) is characterized by a facial gestalt involving prominent forehead, proptosis, downslanting palpebral fissures, broad nasal bridge, thin upper lip, and pointed chin. Affected individuals are tall, with an elongated lower segment, and have large hands and feet. Skin is hyperelastic and fragile. Patients exhibit progressive dilatory and vascular changes in basilar/vertebral and coronary arteries starting in the teenage years (Takenouchi et al., 2015; Takenouchi et al., 2021).
Au-Kline syndrome
MedGen UID:
900671
Concept ID:
C4225274
Disease or Syndrome
Au-Kline syndrome is characterized by developmental delay and hypotonia with moderate-to-severe intellectual disability, and typical facial features that include long palpebral fissures, ptosis, shallow orbits, large and deeply grooved tongue, broad nose with a wide nasal bridge, and downturned mouth. There is frequently variable autonomic dysfunction (gastrointestinal dysmotility, high pain threshold, heat intolerance, recurrent fevers, abnormal sweating). Congenital heart disease, hydronephrosis, palate abnormalities, and oligodontia are also reported in the majority of affected individuals. Additional complications can include craniosynostosis, feeding difficulty, vision issues, osteopenia, and other skeletal anomalies.
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome
MedGen UID:
894399
Concept ID:
C4225285
Disease or Syndrome
Klippel-Feil syndrome-4 with nemaline myopathy and facial dysmorphism (KFS4) is an autosomal recessive disorder characterized mainly by severe hypotonia apparent from infancy. Klippel-Feil anomaly is primarily defined by fusion of the cervical spine, with associated low posterior hairline and limited neck mobility being observed in about half of patients (summary by Alazami et al., 2015). For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100).
Gaze palsy, familial horizontal, with progressive scoliosis 1
MedGen UID:
1647423
Concept ID:
C4551964
Disease or Syndrome
HGPPS is an autosomal recessive neurologic disorder characterized by eye movement abnormalities apparent from birth and childhood-onset progressive scoliosis. These features are associated with a developmental malformation of the brainstem including hypoplasia of the pons and cerebellar peduncles and defective decussation of certain neuronal systems. Cognitive function is normal (summary by Bosley et al., 2005). Genetic Heterogeneity of Familial Horizontal Gaze Palsy With Progressive Scoliosis See also HGPPS2 (617542), caused by mutation in the DCC gene (120470) on chromosome 18q21.
Regressive spondylometaphyseal dysplasia
MedGen UID:
1648288
Concept ID:
C4747922
Disease or Syndrome
Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly (SKPHA) is an autosomal recessive disorder characterized by rhizomelic skeletal dysplasia of variable severity with or without abnormal nuclear shape and chromatin organization in blood granulocytes (Hoffmann et al., 2002; Borovik et al., 2013; Collins et al., 2020). Initial skeletal features may improve with age (Sobreira et al., 2014).
Neurodevelopmental disorder with or without variable brain abnormalities; NEDBA
MedGen UID:
1675664
Concept ID:
C5193102
Disease or Syndrome
Neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) is characterized by global developmental delay apparent from infancy or early childhood, resulting in mildly delayed walking, variably impaired intellectual development, and poor or absent speech. Additional features may include hypotonia, spasticity, or ataxia. About half of patients have abnormal findings on brain imaging, including cerebral or cerebellar atrophy, loss of white matter volume, thin corpus callosum, and perisylvian polymicrogyria. Seizures are not a prominent finding, and although some patients may have nonspecific dysmorphic facial features, there is no common or consistent gestalt (summary by Platzer et al., 2019).
Hyper-IgE recurrent infection syndrome 4, autosomal recessive
MedGen UID:
1673363
Concept ID:
C5193141
Disease or Syndrome
Hyper-IgE syndrome-4B with recurrent infections (HIES4B) is an autosomal recessive immunologic disorder characterized by early childhood onset of recurrent infections and skeletal abnormalities, including craniosynostosis and scoliosis. Patients are mainly susceptible to bacterial infections that affect the respiratory tract, skin, and eye. Immunologic workup shows increased serum IgE, intermittent eosinophilia, and impaired IL6 (147620) and IL27 (608273) downstream signaling that affects the development and function of certain B- and T-cell populations, as well as the acute-phase response; IL11 (147681) signaling in fibroblasts is also affected (summary by Shahin et al., 2019). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see HIES1 (147060).
Autosomal recessive Robinow syndrome
MedGen UID:
1770070
Concept ID:
C5399974
Disease or Syndrome
ROR2-related Robinow syndrome is characterized by distinctive craniofacial features, skeletal abnormalities, and other anomalies. Craniofacial features include macrocephaly, broad prominent forehead, low-set ears, ocular hypertelorism, prominent eyes, midface hypoplasia, short upturned nose with depressed nasal bridge and flared nostrils, large and triangular mouth with exposed incisors and upper gums, gum hypertrophy, misaligned teeth, ankyloglossia, and micrognathia. Skeletal abnormalities include short stature, mesomelic or acromesomelic limb shortening, hemivertebrae with fusion of thoracic vertebrae, and brachydactyly. Other common features include micropenis with or without cryptorchidism in males and reduced clitoral size and hypoplasia of the labia majora in females, renal tract abnormalities, and nail hypoplasia or dystrophy. The disorder is recognizable at birth or in early childhood.
Neurodevelopmental disorder with hypotonia and dysmorphic facies
MedGen UID:
1794184
Concept ID:
C5561974
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and dysmorphic facies (NEDHYDF) is characterized by global developmental delay and hypotonia apparent from birth. Affected individuals have variably impaired intellectual development, often with speech delay and delayed walking. Seizures are generally not observed, although some patients may have single seizures or late-onset epilepsy. Most patients have prominent dysmorphic facial features. Additional features may include congenital cardiac defects (without arrhythmia), nonspecific renal anomalies, joint contractures or joint hyperextensibility, dry skin, and cryptorchidism. There is significant phenotypic variability in both the neurologic and extraneurologic manifestations (summary by Tan et al., 2022).
Progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome
MedGen UID:
1800305
Concept ID:
C5568882
Disease or Syndrome
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of global developmental delay and intellectual disability, progressive spondyloepimetaphyseal dysplasia, short stature, short fourth metatarsals and dysmorphic craniofacial features (including microcephaly, hypertelorism, epicanthal folds, mild ptosis, strabismus, malar hypoplasia, short nose, depressed nasal bridge, full lips, small, low-set ears and short neck). Craniosynostosis, generalized hypotonia, as well as asymmetry of the cerebral hemispheres and mild thinning of the corpus callosum on brain imaging have also been described.
Intellectual developmental disorder, autosomal dominant 73
MedGen UID:
1841272
Concept ID:
C5830636
Mental or Behavioral Dysfunction
Autosomal dominant intellectual developmental disorder-73 (MRD73) is a highly variable neurodevelopmental disorder characterized by impaired intellectual development that ranges from mild to severe, speech delay, behavioral abnormalities, and nonspecific dysmorphic facial features (Janssen et al., 2022).

Professional guidelines

PubMed

Aurégan JC, Odent T, Coyle RM, Miladi L, Wicart P, Dubousset J, Le Merrer M, Padovani JP, Glorion C
Spine (Phila Pa 1976) 2014 Apr 20;39(9):E564-75. doi: 10.1097/BRS.0000000000000260. PMID: 24503682
Aulisa AG, Guzzanti V, Perisano C, Marzetti E, Falciglia F, Aulisa L
Spine (Phila Pa 1976) 2012 Jun 1;37(13):E786-91. doi: 10.1097/BRS.0b013e31824b547d. PMID: 22281476
Costelvi A, Rowley JG
J Fla Med Assoc 1979 Jan;66(1):71-3. PMID: 762529

Recent clinical studies

Etiology

Diebo BG, Tataryn Z, Alsoof D, Lafage R, Hart RA, Passias PG, Ames CP, Scheer JK, Lewis SJ, Shaffrey CI, Burton DC, Deviren V, Line BG, Soroceanu A, Hamilton DK, Klineberg EO, Mundis GM, Kim HJ, Gum JL, Smith JS, Uribe JS, Kelly MP, Kebaish KM, Gupta MC, Nunley PD, Eastlack RK, Hostin R, Protopsaltis TS, Lenke LG, Schwab FJ, Bess S, Lafage V, Daniels AH; the International Spine Study Group
J Bone Joint Surg Am 2023 Sep 20;105(18):1410-1419. Epub 2023 Jul 21 doi: 10.2106/JBJS.23.00031. PMID: 37478308
Zhu F, Zhang Y, Wang G, Ning Y, Leng X, Huang B
World Neurosurg 2023 Feb;170:43-53. Epub 2022 Nov 26 doi: 10.1016/j.wneu.2022.11.089. PMID: 36442784
Gardner A, Berryman F, Pynsent P
J Anat 2022 Aug;241(2):437-446. Epub 2022 Apr 4 doi: 10.1111/joa.13662. PMID: 35373348Free PMC Article
Lee CS, Park KB, Hwang CJ, Cho JH, Lee DH, Park S
Spine J 2022 Mar;22(3):463-471. Epub 2021 Sep 16 doi: 10.1016/j.spinee.2021.09.002. PMID: 34537354
Simon J, Longis PM, Passuti N
Orthop Traumatol Surg Res 2017 Apr;103(2):285-290. Epub 2016 Dec 23 doi: 10.1016/j.otsr.2016.10.021. PMID: 28017875

Diagnosis

Sari DM, Biben V, Wiwaha G, Hilmanto D
Eur J Med Res 2023 Mar 20;28(1):130. doi: 10.1186/s40001-023-01098-3. PMID: 36941660Free PMC Article
Kempers MJ, Wessels M, Van Berendoncks A, van de Laar IM, de Leeuw N, Loeys B
Eur J Med Genet 2022 Oct;65(10):104593. Epub 2022 Aug 11 doi: 10.1016/j.ejmg.2022.104593. PMID: 35964930
Linek P, Wolny T, Myśliwiec A, Klepek A
Biomed Mater Eng 2020;31(2):131-142. doi: 10.3233/BME-201085. PMID: 32474461
Chang DG, Suk SI, Song KS, Kim YH, Oh IS, Kim SI, Park HY, Kim GU, Lee JW, Park JB, Ha KY
World Neurosurg 2019 Dec;132:e472-e478. Epub 2019 Aug 27 doi: 10.1016/j.wneu.2019.08.110. PMID: 31470145
Li Z, Liang J, Shen J, Qiu G, Weng X
Medicine (Baltimore) 2016 Feb;95(5):e2613. doi: 10.1097/MD.0000000000002613. PMID: 26844472Free PMC Article

Therapy

Mohanty S, Hassan FM, Lenke LG, Burton D, Daniels AH, Gupta MC, Kebaish KM, Kelly M, Kim HJ, Klineberg EO, Passias PG, Protopsaltis T, Schwab F, Shaffrey CI, Smith JS, Line BG, Lafage R, Lafage V, Bess S
J Neurosurg Spine 2023 Aug 1;39(2):157-167. Epub 2023 Apr 28 doi: 10.3171/2023.3.SPINE221311. PMID: 37119105
Linek P, Pałac M, Wolny T
Sci Rep 2021 Mar 16;11(1):6026. doi: 10.1038/s41598-021-85552-4. PMID: 33727639Free PMC Article
Farshad M, Frey A, Jentzsch T, Betz M, Widmer J, Spirig JM
BMC Musculoskelet Disord 2021 Feb 23;22(1):216. doi: 10.1186/s12891-021-04083-1. PMID: 33622298Free PMC Article
Serhan Er M, Abousamra O, Rogers K, Akyol Y, Palocaren T, Takemitsu M, Campbell JW, Mackenzie WG
J Pediatr Orthop 2017 Oct/Nov;37(7):466-472. doi: 10.1097/BPO.0000000000000702. PMID: 26683502
Halm H, Niemeyer T, Link T, Liljenqvist U
Eur Spine J 2000 Jun;9(3):191-7. doi: 10.1007/s005860000139. PMID: 10905435Free PMC Article

Prognosis

Diebo BG, Tataryn Z, Alsoof D, Lafage R, Hart RA, Passias PG, Ames CP, Scheer JK, Lewis SJ, Shaffrey CI, Burton DC, Deviren V, Line BG, Soroceanu A, Hamilton DK, Klineberg EO, Mundis GM, Kim HJ, Gum JL, Smith JS, Uribe JS, Kelly MP, Kebaish KM, Gupta MC, Nunley PD, Eastlack RK, Hostin R, Protopsaltis TS, Lenke LG, Schwab FJ, Bess S, Lafage V, Daniels AH; the International Spine Study Group
J Bone Joint Surg Am 2023 Sep 20;105(18):1410-1419. Epub 2023 Jul 21 doi: 10.2106/JBJS.23.00031. PMID: 37478308
Gardner A, Berryman F, Pynsent P
J Anat 2022 Aug;241(2):437-446. Epub 2022 Apr 4 doi: 10.1111/joa.13662. PMID: 35373348Free PMC Article
Lee CS, Park KB, Hwang CJ, Cho JH, Lee DH, Park S
Spine J 2022 Mar;22(3):463-471. Epub 2021 Sep 16 doi: 10.1016/j.spinee.2021.09.002. PMID: 34537354
Simon J, Longis PM, Passuti N
Orthop Traumatol Surg Res 2017 Apr;103(2):285-290. Epub 2016 Dec 23 doi: 10.1016/j.otsr.2016.10.021. PMID: 28017875
Perdriolle R, Vidal J
Spine (Phila Pa 1976) 1985 Nov;10(9):785-91. doi: 10.1097/00007632-198511000-00001. PMID: 4089651

Clinical prediction guides

Diebo BG, Tataryn Z, Alsoof D, Lafage R, Hart RA, Passias PG, Ames CP, Scheer JK, Lewis SJ, Shaffrey CI, Burton DC, Deviren V, Line BG, Soroceanu A, Hamilton DK, Klineberg EO, Mundis GM, Kim HJ, Gum JL, Smith JS, Uribe JS, Kelly MP, Kebaish KM, Gupta MC, Nunley PD, Eastlack RK, Hostin R, Protopsaltis TS, Lenke LG, Schwab FJ, Bess S, Lafage V, Daniels AH; the International Spine Study Group
J Bone Joint Surg Am 2023 Sep 20;105(18):1410-1419. Epub 2023 Jul 21 doi: 10.2106/JBJS.23.00031. PMID: 37478308
Gardner A, Berryman F, Pynsent P
J Anat 2022 Aug;241(2):437-446. Epub 2022 Apr 4 doi: 10.1111/joa.13662. PMID: 35373348Free PMC Article
Lee CS, Park KB, Hwang CJ, Cho JH, Lee DH, Park S
Spine J 2022 Mar;22(3):463-471. Epub 2021 Sep 16 doi: 10.1016/j.spinee.2021.09.002. PMID: 34537354
Plais N, Bao H, Lafage R, Gupta M, Smith JS, Shaffrey C, Mundis G, Burton D, Ames C, Klineberg E, Bess S, Schwab F, Lafage V; International Spine Study Group
Spine Deform 2020 Feb;8(1):105-113. Epub 2020 Jan 24 doi: 10.1007/s43390-020-00046-z. PMID: 31981146
Simon J, Longis PM, Passuti N
Orthop Traumatol Surg Res 2017 Apr;103(2):285-290. Epub 2016 Dec 23 doi: 10.1016/j.otsr.2016.10.021. PMID: 28017875

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