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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

Definition

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). [from OMIM]

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

Bonfanti R, Iafusco D, Rabbone I, Diedenhofen G, Bizzarri C, Patera PI, Reinstadler P, Costantino F, Calcaterra V, Iughetti L, Savastio S, Favia A, Cardella F, Lo Presti D, Girtler Y, Rabbiosi S, D'Annunzio G, Zanfardino A, Piscopo A, Casaburo F, Pintomalli L, Russo L, Grasso V, Minuto N, Mucciolo M, Novelli A, Marucci A, Piccini B, Toni S, Silvestri F, Carrera P, Rigamonti A, Frontino G, Trada M, Tinti D, Delvecchio M, Rapini N, Schiaffini R, Mammì C, Barbetti F; Diabetes Study Group of ISPED
Eur J Endocrinol 2021 Apr;184(4):575-585. doi: 10.1530/EJE-20-1030. PMID: 33606663
Gopi S, Kavitha B, Kanthimathi S, Kannan A, Kumar R, Joshi R, Kanodia S, Arya AD, Pendsey S, Pendsey S, Raghupathy P, Mohan V, Radha V
Pediatr Diabetes 2021 Feb;22(1):82-92. Epub 2020 Sep 15 doi: 10.1111/pedi.13109. PMID: 32893419
Li W, Zhang X, Sun Y, Liu Z
Pharmazie 2020 Jun 1;75(6):230-235. doi: 10.1691/ph.2020.0409. PMID: 32539915

Recent clinical studies

Etiology

Dhayalan B, Weiss MA
Curr Diab Rep 2022 Feb;22(2):85-94. Epub 2022 Feb 4 doi: 10.1007/s11892-022-01447-2. PMID: 35119630
Bonfanti R, Iafusco D, Rabbone I, Diedenhofen G, Bizzarri C, Patera PI, Reinstadler P, Costantino F, Calcaterra V, Iughetti L, Savastio S, Favia A, Cardella F, Lo Presti D, Girtler Y, Rabbiosi S, D'Annunzio G, Zanfardino A, Piscopo A, Casaburo F, Pintomalli L, Russo L, Grasso V, Minuto N, Mucciolo M, Novelli A, Marucci A, Piccini B, Toni S, Silvestri F, Carrera P, Rigamonti A, Frontino G, Trada M, Tinti D, Delvecchio M, Rapini N, Schiaffini R, Mammì C, Barbetti F; Diabetes Study Group of ISPED
Eur J Endocrinol 2021 Apr;184(4):575-585. doi: 10.1530/EJE-20-1030. PMID: 33606663
Gaál Z, Balogh I
Exp Suppl 2019;111:385-416. doi: 10.1007/978-3-030-25905-1_18. PMID: 31588541
Cordiner RLM, Pearson ER
Diabetes Obes Metab 2019 Apr;21(4):761-771. Epub 2019 Feb 11 doi: 10.1111/dom.13596. PMID: 30471177
Bowman P, Day J, Torrens L, Shepherd MH, Knight BA, Ford TJ, Flanagan SE, Chakera A, Hattersley AT, Zeman A
Diabetes Care 2019 Feb;42(2):215-224. Epub 2018 Oct 30 doi: 10.2337/dc18-1060. PMID: 30377186Free PMC Article

Diagnosis

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
Kota AS, Kumar K, Ejaz S
Neoreviews 2020 Jan;21(1):e52-e54. doi: 10.1542/neo.21-1-e52. PMID: 31894084
Antosik K, Borowiec M
Arch Immunol Ther Exp (Warsz) 2016 Dec;64(Suppl 1):157-160. Epub 2017 Jan 12 doi: 10.1007/s00005-016-0432-8. PMID: 28083605
Singh P, Rao SC, Parikh R
Indian J Pediatr 2014 Dec;81(12):1387-8. Epub 2014 Jun 10 doi: 10.1007/s12098-014-1486-4. PMID: 24912436

Therapy

Razzaghy-Azar M, Nourbakhsh M, Talea A, Mohammad Amoli M, Nourbakhsh M, Larijani B
J Med Case Rep 2021 Oct 25;15(1):535. doi: 10.1186/s13256-021-03052-5. PMID: 34696808Free PMC Article
Li W, Zhang X, Sun Y, Liu Z
Pharmazie 2020 Jun 1;75(6):230-235. doi: 10.1691/ph.2020.0409. PMID: 32539915
Cordiner RLM, Pearson ER
Diabetes Obes Metab 2019 Apr;21(4):761-771. Epub 2019 Feb 11 doi: 10.1111/dom.13596. PMID: 30471177
Ioacara S, Flanagan S, Fröhlich-Reiterer E, Goland R, Fica S
J Diabetes Investig 2017 Sep;8(5):716-719. Epub 2017 Feb 16 doi: 10.1111/jdi.12620. PMID: 28083968Free PMC Article
Singh P, Rao SC, Parikh R
Indian J Pediatr 2014 Dec;81(12):1387-8. Epub 2014 Jun 10 doi: 10.1007/s12098-014-1486-4. PMID: 24912436

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
Gaál Z, Balogh I
Exp Suppl 2019;111:385-416. doi: 10.1007/978-3-030-25905-1_18. PMID: 31588541
Nagashima K, Tanaka D, Inagaki N
Pediatr Int 2017 Feb;59(2):129-133. doi: 10.1111/ped.13199. PMID: 27809389
Abujbara MA, Liswi MI, El-Khateeb MS, Flanagan SE, Ellard S, Ajlouni KM
J Pediatr Endocrinol Metab 2014 Sep;27(9-10):879-83. doi: 10.1515/jpem-2014-0069. PMID: 24825091

Clinical prediction guides

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
Bowman P, Day J, Torrens L, Shepherd MH, Knight BA, Ford TJ, Flanagan SE, Chakera A, Hattersley AT, Zeman A
Diabetes Care 2019 Feb;42(2):215-224. Epub 2018 Oct 30 doi: 10.2337/dc18-1060. PMID: 30377186Free PMC Article
Riahi Y, Israeli T, Cerasi E, Leibowitz G
Diabetes Obes Metab 2018 Sep;20 Suppl 2:95-103. doi: 10.1111/dom.13379. PMID: 30230182
Al Senani A, Hamza N, Al Azkawi H, Al Kharusi M, Al Sukaiti N, Al Badi M, Al Yahyai M, Johnson M, De Franco E, Flanagan S, Hattersley A, Ellard S, Mula-Abed WA
J Pediatr Endocrinol Metab 2018 Jan 26;31(2):195-204. doi: 10.1515/jpem-2017-0284. PMID: 29329106Free 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

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