Yuan-Harel-Lupski Syndrome (YUHAL)

Categories: Fetal diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Yuan-Harel-Lupski Syndrome

MalaCards integrated aliases for Yuan-Harel-Lupski Syndrome:

Name: Yuan-Harel-Lupski Syndrome 56 25 58
Pmp22-Rai1 Contiguous Gene Duplication Syndrome 25 58
17p11.2p12 Microduplication Syndrome 58
Trisomy 17p11.2-P12 58
Trisomy 17p11.2p12 58
Dup(17)(p11.2p12) 58
Yuhal Syndrome 25
Yuhal 56



autosomal dominant

onset at birth
onset of peripheral neuropathy in the first decade
genomic duplications occur de novo
pmp22 and rai1 are included in smallest region of overlap


yuan-harel-lupski syndrome:
Inheritance autosomal dominant inheritance
Onset and clinical course congenital onset


Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis

Summaries for Yuan-Harel-Lupski Syndrome

Genetics Home Reference : 25 Yuan-Harel-Lupski (YUHAL) syndrome is a rare neurological condition that has a combination of features of two other disorders, Potocki-Lupski syndrome and type 1A Charcot-Marie-Tooth disease. The first signs and symptoms of YUHAL syndrome begin in infancy. Infants with YUHAL syndrome usually have weak muscle tone (hypotonia), which may lead to feeding problems. They typically do not grow and gain weight at the expected rate. Babies and children with YUHAL syndrome have delayed development, including delayed speech and language skills and motor skills such as walking. YUHAL syndrome is also associated with behavioral difficulties. Many affected individuals have sleep problems, including pauses in breathing during sleep (sleep apnea) or trouble falling asleep and staying asleep. Some people with YUHAL syndrome have subtle differences in facial features, including outside corners of the eyes that point downward (down-slanting palpebral fissures), a triangular face, and eyes that do not look in the same direction (strabismus). These signs and symptoms are similar to those of Potocki-Lupski syndrome. Other signs and symptoms of YUHAL syndrome begin in childhood and result from damage to peripheral nerves, which connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat. Damage to peripheral nerves can lead to loss of sensation and wasting (atrophy) of muscles in the legs. Children with YUHAL syndrome often develop muscle weakness, particularly in the lower legs, which may lead to an unusual walking style (gait). Some affected individuals have foot abnormalities such as flat feet (pes planus), high arches (pes cavus), or an inward- and upward-turning foot (clubfoot). They may also experience reduced reflexes and a decreased sensitivity to touch, heat, and cold in the feet and lower legs. Similar features are seen in individuals with type 1A Charcot-Marie-Tooth disease, although they may appear earlier in people with YUHAL syndrome, often before age 5. Abnormal development of other tissues and organs, such as the heart or kidneys, can occur in YUHAL syndrome.

MalaCards based summary : Yuan-Harel-Lupski Syndrome, also known as pmp22-rai1 contiguous gene duplication syndrome, is related to smith-magenis syndrome and charcot-marie-tooth disease, demyelinating, type 1a. An important gene associated with Yuan-Harel-Lupski Syndrome is YUHAL (Yuan-Harel-Lupski Syndrome). Affiliated tissues include heart, brain and eye, and related phenotypes are syringomyelia and global developmental delay

OMIM : 56 Yuan-Harel-Lupski syndrome is a complex neurodevelopmental disorder characterized by global developmental delay and early-onset peripheral neuropathy. The disorder comprises features of both demyelinating Charcot-Marie-Tooth disease type 1A (CMT1A; 118220), which results from duplication of the PMP22 gene on 17p12, and Potocki-Lupski syndrome (PTLS; 610883), which results from duplication of a slightly proximal region on 17p11.2 that includes the RAI1 gene. These 2 loci are about 2.5 Mb apart. The resultant YUHAL phenotype may be more severe in comparison to the individual contributions of each gene, with particularly early onset of peripheral neuropathy and features of both central and peripheral nervous system involvement (summary by Yuan et al., 2015). (616652)

Related Diseases for Yuan-Harel-Lupski Syndrome

Diseases related to Yuan-Harel-Lupski Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 smith-magenis syndrome 10.4
2 charcot-marie-tooth disease, demyelinating, type 1a 10.3
3 potocki-lupski syndrome 10.3
4 alacrima, achalasia, and mental retardation syndrome 10.3
5 charcot-marie-tooth disease 10.3
6 tooth disease 10.3
7 polyneuropathy 10.3
8 hypotonia 10.3

Graphical network of the top 20 diseases related to Yuan-Harel-Lupski Syndrome:

Diseases related to Yuan-Harel-Lupski Syndrome

Symptoms & Phenotypes for Yuan-Harel-Lupski Syndrome

Human phenotypes related to Yuan-Harel-Lupski Syndrome:

58 31 (show top 50) (show all 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 syringomyelia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003396
2 global developmental delay 58 31 Very frequent (99-80%) HP:0001263
3 smooth philtrum 58 31 Occasional (29-5%) HP:0000319
4 strabismus 58 31 Occasional (29-5%) HP:0000486
5 decreased nerve conduction velocity 58 31 Occasional (29-5%) HP:0000762
6 abnormality of the foot 58 31 Frequent (79-30%) HP:0001760
7 joint laxity 58 31 Frequent (79-30%) HP:0001388
8 thin upper lip vermilion 58 31 Occasional (29-5%) HP:0000219
9 chronic constipation 58 31 Frequent (79-30%) HP:0012450
10 wide nose 58 31 Occasional (29-5%) HP:0000445
11 triangular face 58 31 Occasional (29-5%) HP:0000325
12 distal sensory impairment 58 31 Frequent (79-30%) HP:0002936
13 broad-based gait 58 31 Occasional (29-5%) HP:0002136
14 delayed ability to walk 58 31 Very frequent (99-80%) HP:0031936
15 intellectual disability 31 HP:0001249
16 failure to thrive 31 HP:0001508
17 sleep disturbance 58 Frequent (79-30%)
18 high palate 31 HP:0000218
19 behavioral abnormality 58 Frequent (79-30%)
20 delayed speech and language development 58 Very frequent (99-80%)
21 pes planus 58 Occasional (29-5%)
22 abnormal facial shape 58 Very frequent (99-80%)
23 feeding difficulties 31 HP:0011968
24 downslanted palpebral fissures 58 Occasional (29-5%)
25 ventricular septal defect 58 Occasional (29-5%)
26 feeding difficulties in infancy 58 Very frequent (99-80%)
27 long philtrum 58 Occasional (29-5%)
28 generalized hypotonia 31 HP:0001290
29 areflexia 31 HP:0001284
30 sensory neuropathy 58 Occasional (29-5%)
31 failure to thrive in infancy 58 Frequent (79-30%)
32 atrial septal defect 58 Occasional (29-5%)
33 bicuspid aortic valve 58 Occasional (29-5%)
34 gait ataxia 31 HP:0002066
35 abnormality of the pinna 58 Occasional (29-5%)
36 talipes equinovarus 58 Occasional (29-5%)
37 upslanted palpebral fissure 31 HP:0000582
38 2-3 toe syndactyly 58 Occasional (29-5%)
39 poor speech 31 HP:0002465
40 patent foramen ovale 58 Occasional (29-5%)
41 double outlet right ventricle 58 Occasional (29-5%)
42 infantile muscular hypotonia 58 Very frequent (99-80%)
43 abnormal cardiac septum morphology 31 HP:0001671
44 sandal gap 58 Occasional (29-5%)
45 brain imaging abnormality 58 Frequent (79-30%)
46 abnormal heart morphology 58 Frequent (79-30%)
47 overriding aorta 58 Occasional (29-5%)
48 distal amyotrophy 58 Frequent (79-30%)
49 foot dorsiflexor weakness 58 Frequent (79-30%)
50 distal muscle weakness 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

Neurologic Central Nervous System:
intellectual disability
poor speech
unsteady gait
wide-based gait
ataxic gait
Abdomen Gastrointestinal:
feeding difficulties
chronic constipation

Head And Neck Eyes:
upslanting palpebral fissures

Neurologic Peripheral Nervous System:
demyelinating peripheral neuropathy
distal sensory impairment
decreased nerve conduction velocities
hypo- or areflexia

Cardiovascular Heart:
congenital heart defects (in some patients)
septal defects
aortic defects
aortic valve defects

Head And Neck Nose:
broad nose

Neurologic Behavioral Psychiatric Manifestations:
behavioral abnormalities

Genitourinary Kidneys:
structural renal abnormalities (uncommon)

Growth Other:
failure to thrive

Head And Neck Face:
smooth philtrum
triangular face
dysmorphic facial features, variable (in some patients)

joint laxity

Head And Neck Mouth:
thin upper lip
high-arched palate

Muscle Soft Tissue:
distal muscle atrophy due to peripheral neuropathy
distal muscle weakness due to peripheral neuropathy

Skeletal Feet:
foot deformities

Head And Neck Ears:
ear abnormalities

Clinical features from OMIM:


Drugs & Therapeutics for Yuan-Harel-Lupski Syndrome

Search Clinical Trials , NIH Clinical Center for Yuan-Harel-Lupski Syndrome

Genetic Tests for Yuan-Harel-Lupski Syndrome

Anatomical Context for Yuan-Harel-Lupski Syndrome

MalaCards organs/tissues related to Yuan-Harel-Lupski Syndrome:

Heart, Brain, Eye, Spinal Cord, Kidney

Publications for Yuan-Harel-Lupski Syndrome

Articles related to Yuan-Harel-Lupski Syndrome:

# Title Authors PMID Year
Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The PMP22-RAI1 Contiguous Gene Duplication Syndrome. 61 56
26544804 2015
The clinical spectrum associated with a chromosome 17 short arm proximal duplication (dup 17p11.2) in three patients. 56
18327785 2008
Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies. 56
17457615 2007
A girl with duplication 17p10-p12 associated with a dicentric chromosome. 56
14699617 2004
A dup(17)(p11.2p11.2) detected by fluorescence in situ hybridization in a boy with Alport syndrome. 56
9934986 1999

Variations for Yuan-Harel-Lupski Syndrome

Expression for Yuan-Harel-Lupski Syndrome

Search GEO for disease gene expression data for Yuan-Harel-Lupski Syndrome.

Pathways for Yuan-Harel-Lupski Syndrome

GO Terms for Yuan-Harel-Lupski Syndrome

Sources for Yuan-Harel-Lupski Syndrome

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
54 Novoseek
57 OMIM via Orphanet
61 PubMed
70 Tocris
72 UMLS via Orphanet
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