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Obesity, hyperphagia, and developmental delay(OBHD)

MedGen UID:
462653
Concept ID:
C3151303
Disease or Syndrome
Synonym: OBHD
 
Gene (location): NTRK2 (9q21.33)
 
Monarch Initiative: MONDO:0013483
OMIM®: 613886

Definition

OBHD is a neurodevelopmental disorder characterized by global developmental delay and hyperphagia resulting in obesity. Some patients may develop seizures (summary by Hamdan et al., 2017). [from OMIM]

Clinical features

From HPO
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Polyphagia
MedGen UID:
9369
Concept ID:
C0020505
Finding
A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Motor stereotypies
MedGen UID:
21318
Concept ID:
C0038271
Individual Behavior
Use of the same abnormal action in response to certain triggers or at random. They may be used as a way to regulate one's internal state but must otherwise have no apparent functional purpose.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
Reduced eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
A reduced frequency or duration of eye contact.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.

Professional guidelines

PubMed

Shoemaker A
Diabetes Obes Metab 2024 Apr;26 Suppl 2:25-33. Epub 2024 Feb 21 doi: 10.1111/dom.15494. PMID: 38383825
Duis J, Pullen LC, Picone M, Friedman N, Hawkins S, Sannar E, Pfalzer AC, Shelton AR, Singh D, Zee PC, Glaze DG, Revana A
J Clin Sleep Med 2022 Jun 1;18(6):1687-1696. doi: 10.5664/jcsm.9938. PMID: 35172921Free PMC Article
Yang X
Neuropeptides 2020 Oct;83:102084. Epub 2020 Aug 21 doi: 10.1016/j.npep.2020.102084. PMID: 32859387

Recent clinical studies

Etiology

Kleinendorst L, Abawi O, Vos N, van der Valk ES, Maas SM, Morgan AT, Hildebrand MS, Da Silva JD, Florijn RJ, Lauffer P, Visser JA, van Rossum EFC, van den Akker ELT, van Haelst MM
Clin Obes 2024 Aug;14(4):e12661. Epub 2024 Apr 10 doi: 10.1111/cob.12661. PMID: 38596856
Carvalho LML, Jorge AAL, Bertola DR, Krepischi ACV, Rosenberg C
Curr Obes Rep 2024 Jun;13(2):313-337. Epub 2024 Jan 26 doi: 10.1007/s13679-023-00543-y. PMID: 38277088
Mao S, Yang L, Gao Y, Zou C
Clin Genet 2024 Apr;105(4):415-422. Epub 2024 Jan 23 doi: 10.1111/cge.14477. PMID: 38258470
Basak S, Basak A
Biosci Rep 2022 Jun 30;42(6) doi: 10.1042/BSR20220610. PMID: 35621394Free PMC Article
Cassidy SB, Schwartz S, Miller JL, Driscoll DJ
Genet Med 2012 Jan;14(1):10-26. Epub 2011 Sep 26 doi: 10.1038/gim.0b013e31822bead0. PMID: 22237428

Diagnosis

Shoemaker A
Diabetes Obes Metab 2024 Apr;26 Suppl 2:25-33. Epub 2024 Feb 21 doi: 10.1111/dom.15494. PMID: 38383825
Carvalho LML, Jorge AAL, Bertola DR, Krepischi ACV, Rosenberg C
Curr Obes Rep 2024 Jun;13(2):313-337. Epub 2024 Jan 26 doi: 10.1007/s13679-023-00543-y. PMID: 38277088
Duis J, Pullen LC, Picone M, Friedman N, Hawkins S, Sannar E, Pfalzer AC, Shelton AR, Singh D, Zee PC, Glaze DG, Revana A
J Clin Sleep Med 2022 Jun 1;18(6):1687-1696. doi: 10.5664/jcsm.9938. PMID: 35172921Free PMC Article
Angulo MA, Butler MG, Cataletto ME
J Endocrinol Invest 2015 Dec;38(12):1249-63. Epub 2015 Jun 11 doi: 10.1007/s40618-015-0312-9. PMID: 26062517Free PMC Article
Cassidy SB, Schwartz S, Miller JL, Driscoll DJ
Genet Med 2012 Jan;14(1):10-26. Epub 2011 Sep 26 doi: 10.1038/gim.0b013e31822bead0. PMID: 22237428

Therapy

Gao Y, Yang LL, Dai YL, Shen Z, Zhou Q, Zou CC
Orphanet J Rare Dis 2023 Feb 7;18(1):25. doi: 10.1186/s13023-023-02615-7. PMID: 36750945Free PMC Article
Yang X
Neuropeptides 2020 Oct;83:102084. Epub 2020 Aug 21 doi: 10.1016/j.npep.2020.102084. PMID: 32859387
Kimonis V, Surampalli A, Wencel M, Gold JA, Cowen NM
PLoS One 2019;14(9):e0221615. Epub 2019 Sep 23 doi: 10.1371/journal.pone.0221615. PMID: 31545799Free PMC Article
Pravdivyi I, Ballanyi K, Colmers WF, Wevrick R
Hum Mol Genet 2015 Aug 1;24(15):4276-83. Epub 2015 Apr 29 doi: 10.1093/hmg/ddv159. PMID: 25926624
Bridges N
Arch Dis Child 2014 Feb;99(2):166-70. Epub 2013 Oct 25 doi: 10.1136/archdischild-2013-303760. PMID: 24162007

Prognosis

Kleinendorst L, Abawi O, Vos N, van der Valk ES, Maas SM, Morgan AT, Hildebrand MS, Da Silva JD, Florijn RJ, Lauffer P, Visser JA, van Rossum EFC, van den Akker ELT, van Haelst MM
Clin Obes 2024 Aug;14(4):e12661. Epub 2024 Apr 10 doi: 10.1111/cob.12661. PMID: 38596856
Carvalho LML, Jorge AAL, Bertola DR, Krepischi ACV, Rosenberg C
Curr Obes Rep 2024 Jun;13(2):313-337. Epub 2024 Jan 26 doi: 10.1007/s13679-023-00543-y. PMID: 38277088
Kayadjanian N, Schwartz L, Farrar E, Comtois KA, Strong TV
PLoS One 2018;13(3):e0194655. Epub 2018 Mar 26 doi: 10.1371/journal.pone.0194655. PMID: 29579119Free PMC Article
Hurren BJ, Flack NA
Clin Anat 2016 Jul;29(5):590-605. Epub 2016 Jan 29 doi: 10.1002/ca.22686. PMID: 26749552
Perrone L, Marzuillo P, Grandone A, del Giudice EM
Ital J Pediatr 2010 Jun 11;36:43. doi: 10.1186/1824-7288-36-43. PMID: 20540750Free PMC Article

Clinical prediction guides

McCarthy JM, McCann-Crosby BM, Rech ME, Yin J, Chen CA, Ali MA, Nguyen HN, Miller JL, Schaaf CP
J Med Genet 2018 May;55(5):307-315. Epub 2018 Mar 1 doi: 10.1136/jmedgenet-2017-105024. PMID: 29496979
Hurren BJ, Flack NA
Clin Anat 2016 Jul;29(5):590-605. Epub 2016 Jan 29 doi: 10.1002/ca.22686. PMID: 26749552
Remacle C, Bieswal F, Bol V, Reusens B
Am J Clin Nutr 2011 Dec;94(6 Suppl):1846S-1852S. Epub 2011 May 4 doi: 10.3945/ajcn.110.001651. PMID: 21543546
Perrone L, Marzuillo P, Grandone A, del Giudice EM
Ital J Pediatr 2010 Jun 11;36:43. doi: 10.1186/1824-7288-36-43. PMID: 20540750Free PMC Article
Breier BH, Vickers MH, Ikenasio BA, Chan KY, Wong WP
Mol Cell Endocrinol 2001 Dec 20;185(1-2):73-9. doi: 10.1016/s0303-7207(01)00634-7. PMID: 11738796

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