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Polyendocrine-polyneuropathy syndrome(PEPNS)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonym: PEPNS
SNOMED CT: Polyendocrine polyneuropathy syndrome (1260449002); PEPNS - polyendocrine polyneuropathy syndrome (1260449002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
Concept ID:
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Gene (location): DMXL2 (15q21.2)
Monarch Initiative: MONDO:0014497
OMIM®: 616113
Orphanet: ORPHA453533


A rare genetic disease with characteristics of childhood onset of multiple endocrine manifestations in combination with central and peripheral nervous system abnormalities. Reported signs and symptoms include postnatal growth retardation, moderate intellectual disability, hypogonadotropic hypogonadism, insulin-dependent diabetes mellitus, central hypothyroidism, demyelinating sensorimotor polyneuropathy, cerebellar and pyramidal signs. Progressive hearing loss and a hypoplastic pituitary gland have also been described. Brain imaging shows moderate white matter abnormalities. [from SNOMEDCT_US]

Clinical features

From HPO
Decreased testicular size
MedGen UID:
Concept ID:
Reduced volume of the testicle (the male gonad).
Short stature
MedGen UID:
Concept ID:
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Postnatal growth retardation
MedGen UID:
Concept ID:
Slow or limited growth after birth.
Progressive hearing impairment
MedGen UID:
Concept ID:
A progressive form of hearing impairment.
Cerebellar ataxia
MedGen UID:
Concept ID:
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
MedGen UID:
Concept ID:
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.
Dystonic disorder
MedGen UID:
Concept ID:
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Intellectual disability, moderate
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
MedGen UID:
Concept ID:
Disease or Syndrome
A generalized disorder of peripheral nerves.
Cerebellar hypoplasia
MedGen UID:
Concept ID:
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Motor delay
MedGen UID:
Concept ID:
A type of Developmental delay characterized by a delay in acquiring motor skills.
Anterior pituitary hypoplasia
MedGen UID:
Concept ID:
Congenital Abnormality
Underdevelopment of the anterior pituitary gland.
Abnormality of the sense of smell
MedGen UID:
Concept ID:
An anomaly in the ability to perceive and distinguish scents (odors).
Elevated hemoglobin A1c
MedGen UID:
Concept ID:
An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements.
Diabetes mellitus type 1
MedGen UID:
Concept ID:
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.
MedGen UID:
Concept ID:
Disease or Syndrome
A decreased concentration of glucose in the blood.
Hypogonadotropic hypogonadism
MedGen UID:
Concept ID:
Disease or Syndrome
Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones
Central hypothyroidism
MedGen UID:
Concept ID:
Disease or Syndrome
A type of hypothyroidism due to an insufficient stimulation of an otherwise normal thyroid gland. Central hypothyroidism is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects.
Abnormal thyroid-stimulating hormone level
MedGen UID:
Concept ID:
Any deviation from the normal amount of the thyroid-stimulating hormone (TSH), which is produced by the anterior pituitary gland and stimulates the function of the thyroid gland.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPolyendocrine-polyneuropathy syndrome

Professional guidelines


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Recent clinical studies


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