U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Diabetes mellitus, permanent neonatal 2(PNDM2)

MedGen UID:
1713823
Concept ID:
C5394296
Disease or Syndrome
Synonyms: DIABETES MELLITUS, PERMANENT NEONATAL, 2; PNDM2
 
Gene (location): KCNJ11 (11p15.1)
 
Monarch Initiative: MONDO:0030087
OMIM®: 618856

Disease characteristics

Excerpted from the GeneReview: Permanent Neonatal Diabetes Mellitus
Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to age 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and history of intrauterine growth deficiency. Therapy with insulin and/or oral hypoglycemic medications (in some molecular causes of PNDM) can correct the hyperglycemia and result in dramatic catch-up growth. The course of PNDM varies by genotype. [from GeneReviews]
Authors:
Diva D De León  |  Sara E Pinney   view full author information

Additional description

From OMIM
Permanent neonatal diabetes mellitus-2 (PNDM2) is characterized by onset of insulin-requiring hyperglycemia within the first months of life that requires insulin therapy throughout life. Some patients additionally have marked developmental delay, muscle weakness, and epilepsy (Gloyn et al., 2004). The triad of developmental delay, epilepsy, and neonatal diabetes is known as DEND (Shimomura et al., 2007). Proks et al. (2006) stated that heterozygous activating mutations in KCNJ11 are the most common cause of PNDM and account for 26 to 64% of cases, and that neurologic features are found in 20% of patients with KCNJ11 mutations. For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176).  http://www.omim.org/entry/618856

Clinical features

From HPO
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Bilateral tonic-clonic seizure with focal onset
MedGen UID:
164077
Concept ID:
C0877017
Disease or Syndrome
A bilateral tonic-clonic seizure with focal onset is a focal-onset seizure which progresses into a bilateral tonic-clonic phase.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
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.
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
Diabetes mellitus type 1
MedGen UID:
41522
Concept ID:
C0011854
Disease or Syndrome
Type 1 diabetes mellitus (T1D), also designated insulin-dependent diabetes mellitus (IDDM), is a disorder of glucose homeostasis characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classic phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Hyperglycemia
MedGen UID:
5689
Concept ID:
C0020456
Disease or Syndrome
An increased concentration of glucose in the blood.
Ketoacidosis
MedGen UID:
67434
Concept ID:
C0220982
Disease or Syndrome
Acidosis resulting from accumulation of ketone bodies.
Reduced C-peptide level
MedGen UID:
909412
Concept ID:
C4280764
Finding
A decreased concentration of C-peptide in the circulation. Since C-peptide is secreted in equimolar amounts to insulin, this feature correlates with reduced insulin secretion.
Downturned corners of mouth
MedGen UID:
356471
Concept ID:
C1866195
Anatomical Abnormality
A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.
Bilateral ptosis
MedGen UID:
356120
Concept ID:
C1865916
Disease or Syndrome

Professional guidelines

PubMed

Li W, Zhang X, Sun Y, Liu Z
Pharmazie 2020 Jun 1;75(6):230-235. doi: 10.1691/ph.2020.0409. PMID: 32539915
Gurgel LC, Crispim F, Noffs MH, Belzunces E, Rahal MA, Moisés RS
Diabetes Care 2007 Nov;30(11):e108. doi: 10.2337/dc07-1196. PMID: 17965292
Tonini G, Bizzarri C, Bonfanti R, Vanelli M, Cerutti F, Faleschini E, Meschi F, Prisco F, Ciacco E, Cappa M, Torelli C, Cauvin V, Tumini S, Iafusco D, Barbetti F; Early-Onset Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology
Diabetologia 2006 Sep;49(9):2210-3. Epub 2006 Jul 1 doi: 10.1007/s00125-006-0329-x. PMID: 16816952

Recent clinical studies

Etiology

GBD 2021 Nervous System Disorders Collaborators
Lancet Neurol 2024 Apr;23(4):344-381. Epub 2024 Mar 14 doi: 10.1016/S1474-4422(24)00038-3. PMID: 38493795Free PMC Article
Nuyt AM, Lavoie JC, Mohamed I, Paquette K, Luu TM
Clin Perinatol 2017 Jun;44(2):315-332. Epub 2017 Mar 18 doi: 10.1016/j.clp.2017.01.010. PMID: 28477663
Dessì A, Ottonello G, Fanos V
J Matern Fetal Neonatal Med 2012 Oct;25(Suppl 5):13-8. doi: 10.3109/14767058.2012.714639. PMID: 23025763
Julier C, Nicolino M
Orphanet J Rare Dis 2010 Nov 4;5:29. doi: 10.1186/1750-1172-5-29. PMID: 21050479Free PMC Article
Barker DJ
Nutrition 1997 Sep;13(9):807-13. doi: 10.1016/s0899-9007(97)00193-7. PMID: 9290095

Diagnosis

Redondo MJ, Hagopian WA, Oram R, Steck AK, Vehik K, Weedon M, Balasubramanyam A, Dabelea D
Diabetologia 2020 Oct;63(10):2040-2048. Epub 2020 Sep 7 doi: 10.1007/s00125-020-05211-7. PMID: 32894314Free PMC Article
Sousa M, Bruges-Armas J
Curr Diabetes Rev 2020;16(8):807-819. doi: 10.2174/1573399816666191230114352. PMID: 31886753
Julier C, Nicolino M
Orphanet J Rare Dis 2010 Nov 4;5:29. doi: 10.1186/1750-1172-5-29. PMID: 21050479Free PMC Article
Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL
Hum Mutat 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. PMID: 19790256
Tammaro P
Endocr Dev 2007;11:70-82. doi: 10.1159/000111059. PMID: 17986828

Therapy

Gill V, Kumar V, Singh K, Kumar A, Kim JJ
Biomolecules 2019 Dec 17;9(12) doi: 10.3390/biom9120888. PMID: 31861217Free PMC Article
Cordiner RLM, Pearson ER
Diabetes Obes Metab 2019 Apr;21(4):761-771. Epub 2019 Feb 11 doi: 10.1111/dom.13596. PMID: 30471177
Wiley F
Diabetes Self Manag 2016 Jul-Aug;33(4):36-7. PMID: 27491106
Malecki MT, Skupien J, Klupa T, Wanic K, Mlynarski W, Gach A, Solecka I, Sieradzki J
Diabetes Care 2007 Jan;30(1):147-9. doi: 10.2337/dc06-1628. PMID: 17192350
Greenwood RD, Traisman HS
J Pediatr 1971 Aug;79(2):296-8. doi: 10.1016/s0022-3476(71)80117-8. PMID: 5560053

Prognosis

Laimon W, El-Ziny M, El-Hawary A, Elsharkawy A, Salem NA, Aboelenin HM, Awad MH, Flanagan SE, De Franco E
Acta Diabetol 2021 Dec;58(12):1689-1700. Epub 2021 Aug 23 doi: 10.1007/s00592-021-01788-6. PMID: 34426871
Redondo MJ, Hagopian WA, Oram R, Steck AK, Vehik K, Weedon M, Balasubramanyam A, Dabelea D
Diabetologia 2020 Oct;63(10):2040-2048. Epub 2020 Sep 7 doi: 10.1007/s00125-020-05211-7. PMID: 32894314Free PMC Article
Sousa M, Bruges-Armas J
Curr Diabetes Rev 2020;16(8):807-819. doi: 10.2174/1573399816666191230114352. PMID: 31886753
Julier C, Nicolino M
Orphanet J Rare Dis 2010 Nov 4;5:29. doi: 10.1186/1750-1172-5-29. PMID: 21050479Free PMC Article
Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL
Hum Mutat 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. PMID: 19790256

Clinical prediction guides

Kleinwechter HJ, Weber KS, Liedtke TP, Schäfer-Graf U, Groten T, Rüdiger M, Pecks U
Z Geburtshilfe Neonatol 2024 Feb;228(1):17-31. Epub 2023 Nov 2 doi: 10.1055/a-2180-7715. PMID: 37918833
Redondo MJ, Hagopian WA, Oram R, Steck AK, Vehik K, Weedon M, Balasubramanyam A, Dabelea D
Diabetologia 2020 Oct;63(10):2040-2048. Epub 2020 Sep 7 doi: 10.1007/s00125-020-05211-7. PMID: 32894314Free PMC Article
Hashimoto Y, Dateki S, Hirose M, Satomura K, Sawada H, Mizuno H, Sugihara S, Maruyama K, Urakami T, Sugawara H, Shirai K, Yorifuji T
Pediatr Diabetes 2017 Nov;18(7):532-539. Epub 2016 Sep 29 doi: 10.1111/pedi.12447. PMID: 27681997
Dessì A, Ottonello G, Fanos V
J Matern Fetal Neonatal Med 2012 Oct;25(Suppl 5):13-8. doi: 10.3109/14767058.2012.714639. PMID: 23025763
Hales CN
Br Med Bull 1997 Jan;53(1):109-22. doi: 10.1093/oxfordjournals.bmb.a011594. PMID: 9158288

Recent systematic reviews

Kraus AC, Kucirka LM, Johnson J, AbouNouar A, Connelly SV, Thel HL, Kavi HS, Bailey BM, Fox MK, Malloy K, Conklin JL, Huprich E, Boggess KA
Am J Perinatol 2025 Apr;42(5):630-642. Epub 2024 Sep 13 doi: 10.1055/a-2414-0932. PMID: 39271113
de Mendonça ELSS, de Lima Macêna M, Bueno NB, de Oliveira ACM, Mello CS
Early Hum Dev 2020 Oct;149:105154. Epub 2020 Aug 8 doi: 10.1016/j.earlhumdev.2020.105154. PMID: 32799034
Habeb AM
Libyan J Med 2013 Jun 10;8(1):21137. doi: 10.3402/ljm.v8i0.21137. PMID: 23759358Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...