Pediatric Neurology · Developmental Delay, Epilepsy, and Neonatal Diabetes (DEND) Syndrome

Symptoms, Timelines, and Look-Alikes

At a Glance

DEND syndrome usually begins with neonatal diabetes, while seizures, low muscle tone, and developmental delay may appear later or be subtle. Classic DEND is more severe than iDEND, and comprehensive genetic testing helps distinguish it from other causes of neonatal diabetes.

Navigating a diagnosis of DEND or iDEND means learning to watch for symptoms that may not all appear at the same time. While diabetes is usually the first recognized sign, other features of the syndrome often emerge gradually. Understanding these possibilities can help you stay proactive, but it is important to remember that the absence of a feature does not rule out the condition.

The Variable Presentation of Symptoms

Symptoms of DEND syndrome often appear in stages, but this timeline is not absolute. Neurological manifestations can be recognized very early, may be subtle, or may become apparent only as the child develops ^[1].

1. The Neonatal Period (Birth to 6 Months)

The most common initial sign is neonatal diabetes. This can appear as early as the first few days of life, and is frequently diagnosed within the first month ^[2]^[3]. You might notice high blood sugar readings, excessive thirst, very frequent diaper changes, irritability, or difficulty gaining weight.

2. Early Infancy and Neurological Signs

Neurological symptoms may begin to appear during infancy. In some children, epilepsy (seizures) is noticed at the same time the diabetes is diagnosed ^[4]. Importantly, these seizures may not always look like obvious convulsions. They can sometimes be subtle, such as repetitive movements or brief “staring spells.” Action step: If you see staring or unusual repetitive movements, record a video if it is safe to do so, and seek clinical assessment rather than diagnosing epilepsy on your own.

3. Developmental Markers

Developmental delay usually becomes clearer as the child misses expected milestones, such as holding their head up, making eye contact, or later, sitting and crawling ^[4]^[5]. Hypotonia, or low muscle tone (sometimes described as feeling “floppy”), is also a common early finding that can precede other delays ^[6].

DEND vs. iDEND: What’s the Difference?

Doctors use two different terms to describe the syndrome’s severity, though they exist on a spectrum ^[7].

Classic DEND: This is the more severe form. It includes the full triad: neonatal diabetes, significant developmental delays, and epilepsy ^[7]^[5].
Intermediate DEND (iDEND): This is considered a milder version. Children with iDEND have neonatal diabetes and may have developmental or coordination challenges that are less severe than in classic DEND ^[8]. While iDEND is often described as being “without epilepsy,” some individuals with iDEND-associated mutations may still experience seizures or other brain-related activity ^[9]^[10].

Look-Alike Conditions

Because many different genetic changes can cause high blood sugar in a newborn, your doctor will use comprehensive genetic testing to rule out “look-alike” conditions:

Transient Neonatal Diabetes (6q24): This is the most common cause of transient (temporary) neonatal diabetes. Unlike DEND, these babies are often born very small for their gestational age. The diabetes in these cases usually goes into remission by 18 months, though it may return later in life ^[11]^[12].
Isolated Permanent Neonatal Diabetes (PNDM): Some children have mutations in the exact same genes as DEND (like KCNJ11 or ABCC8) or the INS gene, but the effect is largely limited to the pancreas ^[13]^[14]. They have permanent diabetes without the severe neurological symptoms.
Other Rare Syndromes: Conditions like Wolcott-Rallison syndrome or IPEX syndrome can also cause neonatal diabetes alongside other systemic issues ^[1]^[15].

A Note on Testing: Because a standard genetic sequencing panel alone may miss 6q24 methylation abnormalities or copy-number mechanisms, testing must be a specialist-directed combination of sequencing and appropriate methylation/copy-number analysis to ensure an accurate diagnosis ^[1]^[16].

Common questions in this guide

What are the first signs of DEND syndrome in a baby?

The first recognized sign is usually neonatal diabetes, which may cause high blood sugar, excessive thirst, frequent wet diapers, irritability, or poor weight gain. Seizures, low muscle tone, and developmental differences may appear at the same time or later, and not having one of these features does not rule out DEND syndrome.

How are classic DEND syndrome and iDEND different?

Classic DEND includes neonatal diabetes, significant developmental delay, and epilepsy. iDEND is generally milder and may involve developmental or coordination difficulties without obvious epilepsy, but some children with iDEND-related mutations can still have seizures or other neurological signs.

Could my baby's neonatal diabetes go away?

It depends on the genetic cause. Diabetes related to a 6q24 abnormality often goes into remission by about 18 months but may return later, whereas other forms may be permanent; genetic testing helps clarify the likely course.

Can seizures in DEND syndrome look like staring or repetitive movements?

Yes. Seizures may be subtle and can look like brief staring spells or repeated movements rather than full-body convulsions. If this happens, record a video only if it is safe and seek medical assessment instead of trying to diagnose the event yourself.

What testing distinguishes DEND syndrome from other causes of neonatal diabetes?

A specialist may combine genetic sequencing with testing for 6q24 methylation abnormalities and copy-number changes. A sequencing panel alone can miss some of these findings, so the testing plan should be tailored to the child's presentation.

What other conditions can resemble DEND syndrome?

Look-alikes include 6q24-related transient neonatal diabetes, isolated permanent neonatal diabetes caused by changes in KCNJ11, ABCC8, or INS, and syndromes such as Wolcott-Rallison or IPEX. The pattern of neurological and developmental findings, together with comprehensive genetic testing, helps doctors tell these conditions apart.

What should I do if my child has low muscle tone or delayed milestones?

Low muscle tone and missed milestones should be discussed promptly with the child's medical team. Early-intervention services such as physical or occupational therapy may help support movement and development.

Get notified when new evidence is published on DEND syndrome.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References (16)

1
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2
Novel perspectives of super-high dose sulfonylurea and high-dose oral prednisolone in an infant with DEND syndrome due to V64M heterozygote KCNJ11 mutation.
Barash G, Bassan H, Livne A, et al.
Acta diabetologica 2021; (58(12)):1665-1672 doi:10.1007/s00592-021-01763-1.
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3
Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome.
Yagasaki H, Sano F, Narusawa H, et al.
American journal of medical genetics. Part A 2022; (188(8)):2466-2471 doi:10.1002/ajmg.a.62873.
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4
DEND Syndrome with Heterozygous KCNJ11 Mutation Successfully Treated with Sulfonylurea.
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Journal of Korean medical science 2017; (32(6)):1042-1045 doi:10.3346/jkms.2017.32.6.1042.
PMID: 28480665
5
Case Report: When genetic diagnosis comes late: lessons from a DEND syndrome patient successfully transitioned to sulfonylurea.
Abreu GM, Bastos de Souza R, Bernardo MC, et al.
Frontiers in clinical diabetes and healthcare 2025; (6()):1654037 doi:10.3389/fcdhc.2025.1654037.
PMID: 41169283
6
Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations.
Beltrand J, Elie C, Busiah K, et al.
Diabetes care 2015; (38(11)):2033-41 doi:10.2337/dc15-0837.
PMID: 26438614
7
Permanent Neonatal Diabetes (DEND Syndrome).
Khan SA, Parkash A, Ibrahim M
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 2016; (26(11)):114-115 doi:218.
PMID: 28666500
8
Successful transition to sulfonylurea therapy in two Iraqi siblings with neonatal diabetes mellitus and iDEND syndrome due to ABCC8 mutation.
Ozsu E, Giri D, Seymen Karabulut G, Senniappan S
Journal of pediatric endocrinology & metabolism : JPEM 2016; (29(12)):1403-1406.
PMID: 27849623
9
Case report: Neonatal diabetes mellitus caused by KCNJ11 mutation presenting with intracranial hemorrhage.
Wu B, Xu W
Frontiers in neurology 2023; (14()):1072078 doi:10.3389/fneur.2023.1072078.
PMID: 36937531
10
First case of neonatal diabetes with KCNJ11 Q52R mutation successfully switched from insulin to sulphonylurea treatment.
Ioacara S, Flanagan S, Fröhlich-Reiterer E, et al.
Journal of diabetes investigation 2017; (8(5)):716-719 doi:10.1111/jdi.12620.
PMID: 28083968
11
Chromosome 6q24-related diabetes mellitus.
Yorifuji T, Higuchi S, Hosokawa Y, Kawakita R
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12
Clinical Characteristics and Remission Monitoring of 6q24-Related Transient Neonatal Diabetes.
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13
Molecular and clinical features of KATP -channel neonatal diabetes mellitus in Japan.
Hashimoto Y, Dateki S, Hirose M, et al.
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14
Identification of insulin gene variants in patients with neonatal diabetes in the Chinese population.
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15
The Changing Landscape of Neonatal Diabetes Mellitus in Italy Between 2003 and 2022.
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16
Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach.
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This page is for informational purposes only and does not constitute medical advice. It explains DEND syndrome symptoms and testing, but your child's pediatric neurology, genetics, and diabetes team should interpret their specific signs and results.

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