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Mandibular hypoplasia-deafness-progeroid syndrome(MDPL)

MedGen UID:
811623
Concept ID:
C3715192
Disease or Syndrome
Synonym: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): POLD1 (19q13.33)
 
Monarch Initiative: MONDO:0014157
OMIM®: 615381
Orphanet: ORPHA363649

Definition

Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance, and metabolic abnormalities including insulin resistance and diabetes mellitus. Sensorineural deafness occurs late in the first or second decades of life (summary by Weedon et al., 2013). [from OMIM]

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Sensorineural hearing impairment
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
High pitched voice
MedGen UID:
66836
Concept ID:
C0241703
Finding
An abnormal increase in the pitch (frequency) of the voice.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Lipodystrophy
MedGen UID:
6111
Concept ID:
C0023787
Disease or Syndrome
Degenerative changes of the fat tissue.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Insulin resistance
MedGen UID:
43904
Concept ID:
C0021655
Pathologic Function
Increased resistance towards insulin, that is, diminished effectiveness of insulin in reducing blood glucose levels.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Elevated hepatic transaminase
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
Scleroderma
MedGen UID:
3770
Concept ID:
C0011644
Disease or Syndrome
A chronic autoimmune phenomenon characterized by fibrosis (or hardening) and vascular alterations of the skin.
Telangiectasia
MedGen UID:
21088
Concept ID:
C0039446
Finding
Telangiectasias refer to small dilated blood vessels located near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Telangiectasia are located especially on the tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips.
Dermal atrophy
MedGen UID:
101793
Concept ID:
C0151514
Disease or Syndrome
Partial or complete wasting (atrophy) of the skin.
Lack of skin elasticity
MedGen UID:
892876
Concept ID:
C4021998
Finding
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMandibular hypoplasia-deafness-progeroid syndrome
Follow this link to review classifications for Mandibular hypoplasia-deafness-progeroid syndrome in Orphanet.

Professional guidelines

PubMed

Lee JJ, Sundar KM
Lung 2021 Apr;199(2):87-101. Epub 2021 Mar 13 doi: 10.1007/s00408-021-00426-w. PMID: 33713177
Mohammadieh A, Sutherland K, Cistulli PA
Intern Med J 2017 Nov;47(11):1241-1247. doi: 10.1111/imj.13606. PMID: 29105265
Al-Ani AH, Antoun JS, Thomson WM, Merriman TR, Farella M
Biomed Res Int 2017;2017:9378325. Epub 2017 Mar 19 doi: 10.1155/2017/9378325. PMID: 28401166Free PMC Article

Recent clinical studies

Etiology

Breugem CC, Logjes RJH, Nolte JW, Flores RL
Semin Fetal Neonatal Med 2021 Dec;26(6):101283. Epub 2021 Sep 21 doi: 10.1016/j.siny.2021.101283. PMID: 34663561
Green MA, Resnick CM
Semin Fetal Neonatal Med 2021 Dec;26(6):101280. Epub 2021 Sep 20 doi: 10.1016/j.siny.2021.101280. PMID: 34561178
Lu X, Sawh-Martinez R, Forte AJ, Wu R, Cabrejo R, Wilson A, Steinbacher DM, Alperovich M, Alonso N, Persing JA
Ann Plast Surg 2019 Nov;83(5):568-582. doi: 10.1097/SAP.0000000000001811. PMID: 31008788
Schweiger C, Manica D, Kuhl G
Semin Pediatr Surg 2016 Jun;25(3):123-7. Epub 2016 Feb 18 doi: 10.1053/j.sempedsurg.2016.02.002. PMID: 27301596
Kaneyama K, Segami N, Hatta T
Congenit Anom (Kyoto) 2008 Sep;48(3):118-25. doi: 10.1111/j.1741-4520.2008.00191.x. PMID: 18778456

Diagnosis

Hsieh ST, Woo AS
Clin Plast Surg 2019 Apr;46(2):249-259. Epub 2019 Feb 8 doi: 10.1016/j.cps.2018.11.010. PMID: 30851756
Brandstetter KA, Patel KG
Facial Plast Surg Clin North Am 2016 Nov;24(4):495-515. doi: 10.1016/j.fsc.2016.06.006. PMID: 27712817
Schweiger C, Manica D, Kuhl G
Semin Pediatr Surg 2016 Jun;25(3):123-7. Epub 2016 Feb 18 doi: 10.1053/j.sempedsurg.2016.02.002. PMID: 27301596
Papagrigorakis MJ, Karamolegou M, Vilos G, Apostolidis C, Karamesinis K, Synodinos PN
Angle Orthod 2012 May;82(3):556-64. Epub 2011 Nov 3 doi: 10.2319/052911-356.1. PMID: 22050072Free PMC Article
Mohamed Riyaz SS, Jayachandran S
Indian J Dent Res 2009 Oct-Dec;20(4):508-10. doi: 10.4103/0970-9290.59442. PMID: 20139583

Therapy

Dib-Zakkour J, Flores-Fraile J, Montero-Martin J, Dib-Zakkour S, Dib-Zaitun I
Medicina (Kaunas) 2022 Feb 9;58(2) doi: 10.3390/medicina58020256. PMID: 35208580Free PMC Article
Morrison KA, Collares MV, Flores RL
Clin Plast Surg 2021 Jul;48(3):363-373. Epub 2021 May 8 doi: 10.1016/j.cps.2021.03.005. PMID: 34051891
Moro A, Mattos CFP, Borges SW, Flores-Mir C, Topolski F
J World Fed Orthod 2020 Jun;9(2):56-67. Epub 2020 May 27 doi: 10.1016/j.ejwf.2020.04.003. PMID: 32672656
Tingting X, Danming Y, Xin C
Eur Arch Otorhinolaryngol 2018 Feb;275(2):335-346. Epub 2017 Nov 24 doi: 10.1007/s00405-017-4818-y. PMID: 29177626
Wiedel AP
Swed Dent J Suppl 2015;(238):10-72. PMID: 26939312

Prognosis

Logjes RJH, Breugem CC, Van Haaften G, Paes EC, Sperber GH, van den Boogaard MH, Farlie PG
Am J Med Genet A 2018 Jun;176(6):1349-1368. Epub 2018 Apr 25 doi: 10.1002/ajmg.a.38718. PMID: 29696787
Al-Ani AH, Antoun JS, Thomson WM, Merriman TR, Farella M
Biomed Res Int 2017;2017:9378325. Epub 2017 Mar 19 doi: 10.1155/2017/9378325. PMID: 28401166Free PMC Article
Schweiger C, Manica D, Kuhl G
Semin Pediatr Surg 2016 Jun;25(3):123-7. Epub 2016 Feb 18 doi: 10.1053/j.sempedsurg.2016.02.002. PMID: 27301596
Smith RM, Hassan A, Robertson CE
Curr Pain Headache Rep 2015 Sep;19(9):44. doi: 10.1007/s11916-015-0515-y. PMID: 26210355
Maillefert JF, Gazet-Maillefert MP, Tavernier C, Farge P
Joint Bone Spine 2000;67(2):86-93. PMID: 10769099

Clinical prediction guides

Díaz-Quevedo AA, Castillo-Quispe HML, Atoche-Socola KJ, Arriola-Guillén LE
J Stomatol Oral Maxillofac Surg 2021 Dec;122(6):583-587. Epub 2021 Jan 20 doi: 10.1016/j.jormas.2021.01.007. PMID: 33484855
Elouej S, Harhouri K, Le Mao M, Baujat G, Nampoothiri S, Kayserili H, Menabawy NA, Selim L, Paneque AL, Kubisch C, Lessel D, Rubinsztajn R, Charar C, Bartoli C, Airault C, Deleuze JF, Rötig A, Bauer P, Pereira C, Loh A, Escande-Beillard N, Muchir A, Martino L, Gruenbaum Y, Lee SH, Manivet P, Lenaers G, Reversade B, Lévy N, De Sandre-Giovannoli A
Nat Commun 2020 Sep 11;11(1):4589. doi: 10.1038/s41467-020-18146-9. PMID: 32917887Free PMC Article
Al-Ani AH, Antoun JS, Thomson WM, Merriman TR, Farella M
Biomed Res Int 2017;2017:9378325. Epub 2017 Mar 19 doi: 10.1155/2017/9378325. PMID: 28401166Free PMC Article
Reinier F, Zoledziewska M, Hanna D, Smith JD, Valentini M, Zara I, Berutti R, Sanna S, Oppo M, Cusano R, Satta R, Montesu MA, Jones C, Cerimele D, Nickerson DA, Angius A, Cucca F, Cottoni F, Crisponi L
Metabolism 2015 Nov;64(11):1530-40. Epub 2015 Aug 1 doi: 10.1016/j.metabol.2015.07.022. PMID: 26350127
Plötz FB, van Essen AJ, Bosschaart AN, Bos AP
Am J Med Genet 1996 Mar 29;62(3):286-92. doi: 10.1002/(SICI)1096-8628(19960329)62:3<286::AID-AJMG16>3.0.CO;2-G. PMID: 8882789

Recent systematic reviews

Alam MK, Alfawzan AA, Abutayyem H, Kanwal B, Alswairki HJ, Verma S, Ganji KK, Munisekhar MS, Siddiqui AA, Fahim A
Sci Prog 2023 Jan-Mar;106(1):368504231156297. doi: 10.1177/00368504231156297. PMID: 36803068Free PMC Article
Feltner C, Wallace IF, Aymes S, Cook Middleton J, Hicks KL, Schwimmer M, Baker C, Balio CP, Moore D, Voisin CE, Jonas DE
JAMA 2022 Nov 15;328(19):1951-1971. doi: 10.1001/jama.2022.18357. PMID: 36378203
Alam MK, Alfawzan AA, Srivastava KC, Shrivastava D, Ganji KK, Manay SM
Sci Rep 2022 Apr 5;12(1):5708. doi: 10.1038/s41598-022-09764-y. PMID: 35383244Free PMC Article
Corcuera-Flores JR, Casttellanos-Cosano L, Torres-Lagares D, Serrera-Figallo MÁ, Rodríguez-Caballero Á, Machuca-Portillo G
Clin Anat 2016 Jul;29(5):555-60. Epub 2015 Dec 21 doi: 10.1002/ca.22654. PMID: 26457586
Huynh NT, Desplats E, Almeida FR
Sleep Med Rev 2016 Feb;25:84-94. Epub 2015 Feb 17 doi: 10.1016/j.smrv.2015.02.002. PMID: 26164371

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