Permanent neonatal diabetes mellitus - pancreatic and cerebellar agenesis

General Information (adopted from Orphanet):

Synonyms, Signs: PACA
Pancreatic and cerebellar agenesis
Diabetes mellitus, permanent neonatal, with cerebellar agenesis
Number of Symptoms 34
OrphanetNr: 65288
OMIM Id: 609069
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 4 cases
Inheritance: Autosomal recessive
10507728 [IBIS]
Age of onset: Neonatal
10507728 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic syndrome with a cerebellar malformation as major feature
 -Rare genetic disease
Neonatal diabetes mellitus
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -Rare endocrine disease
 -Rare genetic disease
Syndrome with a cerebellar malformation as major feature
 -Rare developmental defect during embryogenesis
 -Rare neurologic disease

Comment:

Pancreatic and cerebellar agenesis (PACA) can be caused by homozygous mutations in the PTF1A gene (OMIM).

Symptom Information: Sort by abundance 

1
 (HPO:0000609) Optic nerve hypoplasia 10507728; 15543146 IBIS 26 / 7739
2
 (HPO:0000648) Optic atrophy Very frequent [Orphanet] 21749365 IBIS 238 / 7739
3
 (HPO:0000543) Optic disc pallor 10507728; 15543146 IBIS 67 / 7739
4
 (HPO:0000639) Nystagmus 19650412 IBIS 555 / 7739
5
 (HPO:0005972) Respiratory acidosis 10507728 IBIS 3 / 7739
6
 (HPO:0003717) Minimal subcutaneous fat 10507728; 15543146; 19650412 IBIS 4 / 7739
7
 (HPO:0003074) Hyperglycemia 10507728; 15543146; 19650412 IBIS 37 / 7739
8
 (HPO:0001903) Anemia 10507728; 21749365 IBIS 289 / 7739
9
 (HPO:0001319) Neonatal hypotonia 19650412 IBIS 101 / 7739
10
 (HPO:0001336) Myoclonus 19650412 IBIS 115 / 7739
11
 (HPO:0100022) Abnormality of movement 10507728 IBIS 129 / 7739
12
 (HPO:0002353) EEG abnormality 10507728 IBIS 188 / 7739
13
 (HPO:0001250) Seizures 19650412 IBIS 1245 / 7739
14
 (HPO:0001511) Intrauterine growth retardation 10507728; 15543146; 21749365; 19650412 IBIS 358 / 7739
15
 (HPO:0001562) Oligohydramnios 19650412 IBIS 75 / 7739
16
 (HPO:0010557) Overlapping fingers 10507728 IBIS 9 / 7739
17
 (HPO:0001776) Bilateral talipes equinovarus 10507728; 21749365 IBIS 8 / 7739
18
 (HPO:0000768) Pectus carinatum 19650412 IBIS 136 / 7739
19
 (HPO:0001387) Joint stiffness 10507728; 21749365; 19650412 IBIS 322 / 7739
20
 (HPO:0000952) Jaundice 10507728 IBIS 105 / 7739
21
 (HPO:0100800) Aplasia/Hypoplasia of the pancreas 10507728; 15543146; 21749365 IBIS 8 / 7739
22
 (HPO:0001738) Exocrine pancreatic insufficiency 10507728 IBIS 23 / 7739
23
 (HPO:0000331) Short chin 10507728; 21749365; 19650412 IBIS 33 / 7739
24
 (HPO:0000325) Triangular face Very frequent [Orphanet] 10507728; 21749365; 19650412 IBIS 91 / 7739
25
 (HPO:0000444) Convex nasal ridge 10507728; 19650412 IBIS 87 / 7739
26
 (HPO:0000369) Low-set ears Very frequent [Orphanet] hallmark [HPO] 10507728; 19650412 IBIS 372 / 7739
27
 (HPO:0002104) Apnea 10507728 IBIS 106 / 7739
28
 (HPO:0001371) Flexion contracture 15543146 IBIS 220 / 7739
29
 (HPO:0012195) Irregular respiration 10507728; 19650412 IBIS 3 / 7739
30
 (HPO:0002335) Agenesis of cerebellar vermis Very frequent [Orphanet] hallmark [HPO] 15543146 IBIS 25 / 7739
31
 (HPO:0012642) Cerebellar agenesis 10507728; 15543146; 21749365 IBIS 2 / 7739
32
 (HPO:0001321) Cerebellar hypoplasia 10507728; 21749365; 19650412 IBIS 114 / 7739
33
 (HPO:0012448) Delayed myelination 10507728 IBIS 51 / 7739
34
 (MedDRA:10028933) Neonatal diabetes mellitus 10507728; 15543146; 21749365 IBIS 1 / 7739

Associated genes:

PTF1A;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Hoveyda et al. (1999) described neonatal diabetes mellitus with cerebellar hypoplasia/agenesis, and dysmorphism. The patients they observed were referred to as Asian (specifically Pakistani). There was a strong family history of noninsulin-dependent diabetes mellitus (see 125853) in the ...
Molecular genetics OMIM In the consanguineous Pakistani family which Hoveyda et al. (1999) first described the syndrome of pancreatic and cerebellar agenesis, Sellick et al. (2004) found by positional candidate gene approach a mutation in the PTF1A gene (607194.0001). They found ...