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Diabetes-deafness syndrome maternally transmitted(MIDD)

MedGen UID:
90979
Concept ID:
C0342289
Disease or Syndrome
Synonyms: Ballinger Wallace syndrome; Diabetes and Hearing Loss; Diabetes mellitus type II with deafness; Maternally inherited diabetes and deafness; MIDD; NIDDM WITH DEAFNESS; NONINSULIN-DEPENDENT DIABETES MELLITUS WITH DEAFNESS
SNOMED CT: Ballinger-Wallace syndrome (237619009); Diabetes-deafness syndrome maternally transmitted (237619009)
Modes of inheritance:
Mitochondrial inheritance
MedGen UID:
165802
Concept ID:
C0887941
Genetic Function
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on the mitochondrial genome. Because the mitochondrial genome is essentially always maternally inherited, a mitochondrial condition can only be transmitted by females, although the condition can affect both sexes. The proportion of mutant mitochondria can vary (heteroplasmy).
 
Monarch Initiative: MONDO:0010785
OMIM®: 520000
Orphanet: ORPHA225

Definition

Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms (Ballinger et al., 1992; Reardon et al., 1992; Guillausseau et al., 2001). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300), Rogers syndrome (249270), and Herrmann syndrome (172500), but all 3 of these disorders have other clinical manifestations. [from OMIM]

Additional description

From MedlinePlus Genetics
Maternally inherited diabetes and deafness (MIDD) is a form of diabetes that is often accompanied by hearing loss, especially of high tones. The diabetes in MIDD is characterized by high blood sugar (glucose) levels, known as hyperglycemia. This results from a shortage of the hormone insulin, which regulates the amount of glucose in the blood. In MIDD, the diabetes and hearing loss usually develop in mid-adulthood, although the age that they occur varies from childhood to late adulthood. Typically, hearing loss occurs before diabetes.

Some people with MIDD develop an eye disorder called macular retinal dystrophy, which is characterized by colored patches in the light-sensitive tissue that lines the back of the eye (the retina). This disorder does not usually cause vision problems in people with MIDD. Individuals with MIDD also may experience muscle cramps or weakness, particularly during exercise; heart problems; kidney disease; and constipation. Individuals with MIDD are often shorter than their peers.  https://medlineplus.gov/genetics/condition/maternally-inherited-diabetes-and-deafness

Clinical features

From HPO
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Sensorineural hearing loss disorder
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.
Vertigo
MedGen UID:
53006
Concept ID:
C0042571
Sign or Symptom
An abnormal sensation of spinning while the body is actually stationary.
Abnormal vestibular function
MedGen UID:
334848
Concept ID:
C1843865
Finding
An abnormality of the functioning of the vestibular apparatus.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Type 2 diabetes mellitus
MedGen UID:
41523
Concept ID:
C0011860
Disease or Syndrome
Type 2 diabetes mellitus is distinct from maturity-onset diabetes of the young (see 606391) in that it is polygenic, characterized by gene-gene and gene-environment interactions with onset in adulthood, usually at age 40 to 60 but occasionally in adolescence if a person is obese. The pedigrees are rarely multigenerational. The penetrance is variable, possibly 10 to 40% (Fajans et al., 2001). Persons with type 2 diabetes usually have an obese body habitus and manifestations of the so-called metabolic syndrome (see 605552), which is characterized by diabetes, insulin resistance, hypertension, and hypertriglyceridemia. Genetic Heterogeneity of Susceptibility to Type 2 Diabetes Susceptibility to T2D1 (601283) is conferred by variation in the calpain-10 gene (CAPN10; 605286) on chromosome 2q37. The T2D2 locus (601407) on chromosome 12q was found in a Finnish population. The T2D3 locus (603694) maps to chromosome 20. The T2D4 locus (608036) maps to chromosome 5q34-q35. Susceptibility to T2D5 (616087) is conferred by variation in the TBC1D4 gene (612465) on chromosome 13q22. A mutation has been observed in hepatocyte nuclear factor-4-alpha (HNF4A; 600281.0004) in a French family with NIDDM of late onset. Mutations in the NEUROD1 gene (601724) on chromosome 2q32 were found to cause type 2 diabetes mellitus in 2 families. Mutation in the GLUT2 glucose transporter was associated with NIDDM in 1 patient (138160.0001). Mutation in the MAPK8IP1 gene, which encodes the islet-brain-1 protein, was found in a family with type 2 diabetes in individuals in 4 successive generations (604641.0001). Polymorphism in the KCNJ11 gene (600937.0014) confers susceptibility. In French white families, Vionnet et al. (2000) found evidence for a susceptibility locus for type 2 diabetes on 3q27-qter. They confirmed the diabetes susceptibility locus on 1q21-q24 reported by Elbein et al. (1999) in whites and by Hanson et al. (1998) in Pima Indians. A mutation in the GPD2 gene (138430.0001) on chromosome 2q24.1, encoding mitochondrial glycerophosphate dehydrogenase, was found in a patient with type 2 diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX4 gene (167413) have been identified in patients with type 2 diabetes. Triggs-Raine et al. (2002) stated that in the Oji-Cree, a gly319-to-ser change in HNF1-alpha (142410.0008) behaves as a susceptibility allele for type 2 diabetes. Mutation in the HNF1B gene (189907.0007) was found in 2 Japanese patients with typical late-onset type 2 diabetes. Mutations in the IRS1 gene (147545) have been found in patients with type 2 diabetes. A missense mutation in the AKT2 gene (164731.0001) caused autosomal dominant type 2 diabetes in 1 family. A (single-nucleotide polymorphism) SNP in the 3-prime untranslated region of the resistin gene (605565.0001) was associated with susceptibility to diabetes and to insulin resistance-related hypertension in Chinese subjects. Susceptibility to insulin resistance has been associated with polymorphism in the TCF1 (142410.0011), PPP1R3A (600917.0001), PTPN1 (176885.0001), ENPP1 (173335.0006), IRS1 (147545.0002), and EPHX2 (132811.0001) genes. The K121Q polymorphism of ENPP1 (173335.0006) is associated with susceptibility to type 2 diabetes; a haplotype defined by 3 SNPs of this gene, including K121Q, is associated with obesity, glucose intolerance, and type 2 diabetes. A SNP in the promoter region of the hepatic lipase gene (151670.0004) predicts conversion from impaired glucose tolerance to type 2 diabetes. Variants of transcription factor 7-like-2 (TCF7L2; 602228.0001), located on 10q, have also been found to confer risk of type 2 diabetes. A common sequence variant, rs10811661, on chromosome 9p21 near the CDKN2A (600160) and CDKN2B (600431) genes has been associated with risk of type 2 diabetes. Variation in the PPARG gene (601487) has been associated with risk of type 2 diabetes. A promoter polymorphism in the IL6 gene (147620) is associated with susceptibility to NIDDM. Variation in the KCNJ15 gene (602106) has been associated with T2DM in lean Asians. Variation in the SLC30A8 gene (611145) has been associated with susceptibility to T2D. Variation in the HMGA1 gene (600701.0001) is associated with an increased risk of type 2 diabetes. Mutation in the MTNR1B gene (600804) is associated with susceptibility to type 2 diabetes. Protection Against Type 2 Diabetes Mellitus Protein-truncating variants in the SLC30A8 (611145) have been associated with a reduced risk for T2D.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells.
External ophthalmoplegia
MedGen UID:
57662
Concept ID:
C0162292
Disease or Syndrome
Paralysis of the external ocular muscles.
Constriction of peripheral visual field
MedGen UID:
68613
Concept ID:
C0235095
Finding
An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye.
Pigmentary retinopathy
MedGen UID:
1643295
Concept ID:
C4551715
Disease or Syndrome
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDiabetes-deafness syndrome maternally transmitted
Follow this link to review classifications for Diabetes-deafness syndrome maternally transmitted in Orphanet.

Professional guidelines

PubMed

Robinson KN, Terrazas S, Giordano-Mooga S, Xavier NA
Endocr Pract 2020 Feb;26(2):241-246. Epub 2019 Nov 4 doi: 10.4158/EP-2019-0270. PMID: 31682520

Recent clinical studies

Etiology

Almarzooqi F, Vallance H, Mezei M, Lehman A, Horvath G, Rakic B, Zypchen L, Mattman A
Acta Haematol 2023;146(3):220-225. Epub 2023 Feb 10 doi: 10.1159/000529311. PMID: 36774923
Yang M, Xu L, Xu C, Cui Y, Jiang S, Dong J, Liao L
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Finsterer J, Zarrouk-Mahjoub S
Herz 2020 Jun;45(4):356-361. Epub 2018 Aug 20 doi: 10.1007/s00059-018-4739-6. PMID: 30128910
Spaide RF
Retina 2017 Nov;37(11):2008-2014. doi: 10.1097/IAE.0000000000001497. PMID: 28092344
Cavero T, Rabasco C, Molero A, Blázquez A, Hernández E, Martín MA, Praga M
Nefrologia 2015;35(1):6-17. doi: 10.3265/Nefrologia.pre2014.Sep.12728. PMID: 25611829

Diagnosis

Gruber N, Pinhas-Hamiel O
Curr Diab Rep 2022 Sep;22(9):423-432. Epub 2022 Jul 5 doi: 10.1007/s11892-022-01483-y. PMID: 35789979
Yang M, Xu L, Xu C, Cui Y, Jiang S, Dong J, Liao L
Front Endocrinol (Lausanne) 2021;12:728043. Epub 2021 Nov 25 doi: 10.3389/fendo.2021.728043. PMID: 34899594Free PMC Article
Sousa M, Bruges-Armas J
Curr Diabetes Rev 2020;16(8):807-819. doi: 10.2174/1573399816666191230114352. PMID: 31886753
Robinson KN, Terrazas S, Giordano-Mooga S, Xavier NA
Endocr Pract 2020 Feb;26(2):241-246. Epub 2019 Nov 4 doi: 10.4158/EP-2019-0270. PMID: 31682520
Li HZ, Li RY, Li M
Front Biosci (Landmark Ed) 2014 Jan 1;19(5):777-82. doi: 10.2741/4244. PMID: 24389221

Therapy

Zhang X, Chen Y, Tong N, Shao Q, Zhou Y, Mu T, Yang X, Zhang Y
J Diabetes Investig 2022 Feb;13(2):397-401. Epub 2021 Sep 22 doi: 10.1111/jdi.13651. PMID: 34460997Free PMC Article
Müller PL, Treis T, Pfau M, Esposti SD, Alsaedi A, Maloca P, Balaskas K, Webster A, Egan C, Tufail A
Am J Ophthalmol 2020 May;213:134-144. Epub 2020 Jan 24 doi: 10.1016/j.ajo.2020.01.013. PMID: 31987901
Yaribeygi H, Lhaf F, Sathyapalan T, Sahebkar A
Life Sci 2019 Aug 15;231:116538. Epub 2019 Jun 6 doi: 10.1016/j.lfs.2019.06.013. PMID: 31176776
Johnson SC, Martinez F, Bitto A, Gonzalez B, Tazaerslan C, Cohen C, Delaval L, Timsit J, Knebelmann B, Terzi F, Mahal T, Zhu Y, Morgan PG, Sedensky MM, Kaeberlein M, Legendre C, Suh Y, Canaud G
Kidney Int 2019 Feb;95(2):455-466. Epub 2018 Nov 22 doi: 10.1016/j.kint.2018.08.038. PMID: 30471880Free PMC Article
Sack MN, Murphy E
J Cardiovasc Pharmacol Ther 2011 Sep-Dec;16(3-4):267-72. doi: 10.1177/1074248411408313. PMID: 21821527Free PMC Article

Prognosis

Müller PL, Treis T, Pfau M, Esposti SD, Alsaedi A, Maloca P, Balaskas K, Webster A, Egan C, Tufail A
Am J Ophthalmol 2020 May;213:134-144. Epub 2020 Jan 24 doi: 10.1016/j.ajo.2020.01.013. PMID: 31987901
Sousa M, Bruges-Armas J
Curr Diabetes Rev 2020;16(8):807-819. doi: 10.2174/1573399816666191230114352. PMID: 31886753
Holt RIG
Diabet Med 2019 Apr;36(4):397-398. doi: 10.1111/dme.13938. PMID: 30848534
Spaide RF
Retina 2017 Nov;37(11):2008-2014. doi: 10.1097/IAE.0000000000001497. PMID: 28092344
Molven A, Njølstad PR
Expert Rev Mol Diagn 2011 Apr;11(3):313-20. doi: 10.1586/erm.10.123. PMID: 21463240

Clinical prediction guides

Oishi N, Kubota D, Nakamoto K, Takeda Y, Hayashi M, Gocho K, Yamaki K, Igarashi T, Takahashi H, Kameya S
Ophthalmic Genet 2021 Jun;42(3):304-311. Epub 2021 Feb 5 doi: 10.1080/13816810.2021.1881978. PMID: 33541179
Müller PL, Treis T, Pfau M, Esposti SD, Alsaedi A, Maloca P, Balaskas K, Webster A, Egan C, Tufail A
Am J Ophthalmol 2020 May;213:134-144. Epub 2020 Jan 24 doi: 10.1016/j.ajo.2020.01.013. PMID: 31987901
Holt RIG
Diabet Med 2019 Apr;36(4):397-398. doi: 10.1111/dme.13938. PMID: 30848534
Sugai K, Ueda H, Morimoto K, Tanaka M, Takahashi D, Nakashima A, Kato J, Takahashi H, Yamaguchi Y, Kawamura T, Hanaoka K, Miyazaki Y, Yokoo T
BMC Nephrol 2018 Dec 10;19(1):350. doi: 10.1186/s12882-018-1152-6. PMID: 30526529Free PMC Article
Molven A, Njølstad PR
Expert Rev Mol Diagn 2011 Apr;11(3):313-20. doi: 10.1586/erm.10.123. PMID: 21463240

Recent systematic reviews

Ndumele CD, Ableman G, Russell BE, Gurrola E, Hicks LS
J Health Care Poor Underserved 2011 Feb;22(1):5-23. doi: 10.1353/hpu.2011.0031. PMID: 21317503

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