Noonan syndrome-like disorder with loose anagen hair

General Information (adopted from Orphanet):

Synonyms, Signs: NS/LAH
NSLH
Tosti syndrome
Mazzanti Syndrome
Number of Symptoms 79
OrphanetNr: 2701
OMIM Id: 607721
ICD-10: Q87.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 0.1 of 100 000
Inheritance: Autosomal dominant
24451042 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Alopecia
 -Rare genetic disease
 -Rare skin disease
Genetic multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
 -Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
 -Rare developmental defect during embryogenesis
Noonan syndrome and Noonan-related syndrome
 -Rare cardiac disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Syndromic developmental defect of the eye
 -Rare developmental defect during embryogenesis
 -Rare eye disease
 -Rare genetic disease

Comment:

Noonan-like syndrome with loose anagen hair belongs to the group of RASopathies characterized by abnormalities in the RAS-MAPK signaling pathway, which is known to play a major role in lymphangiogenesis. It is caused by a single mutation in SHOC2 ( p.Ser2Gly) promoting N-myristoylation of the encoded protein. Clinical features include facial deformities resembling Noonan syndrome, short stature often associated with proven growth hormone deficiency (GHD), typical ectodermal anomalies, and distinctive behavior. The symptoms are more severe than those generally observed in Noonan syndrome, but improove with age. (PMID:24124081)

Symptom Information: Sort by abundance 

1
 (HPO:0011968) Feeding difficulties 12673660 IBIS 240 / 7739
2
 (HPO:0002013) Vomiting 12673660 IBIS 191 / 7739
3
 (HPO:0000316) Hypertelorism Occasional [Orphanet] 19684605 IBIS 644 / 7739
4
 (HPO:0001090) Large eyes 12673660 IBIS 20 / 7739
5
 (HPO:0000486) Strabismus 12673660 IBIS 576 / 7739
6
 (HPO:0000539) Abnormality of refraction 19684605 IBIS 6 / 7739
7
 (HPO:0000508) Ptosis 12673660; 19684605 IBIS 459 / 7739
8
 (HPO:0001609) Hoarse voice 19684605 IBIS 34 / 7739
9
 (HPO:0001611) Nasal speech rare [HPO:skoehler] 24124081 IBIS 48 / 7739
10
 (HPO:0004322) Short stature Very frequent [IBIS] Very frequent [Orphanet] 24124081 IBIS 1232 / 7739
11
 (HPO:0001531) Failure to thrive in infancy 25846317 IBIS 26 / 7739
12
 (HPO:0002901) Hypocalcemia 12673660 IBIS 56 / 7739
13
 (HPO:0001943) Hypoglycemia 12673660 IBIS 131 / 7739
14
 (HPO:0001631) Atria septal defect 19684605 IBIS 274 / 7739
15
 (HPO:0001629) Ventricular septal defect 19684605 IBIS 316 / 7739
16
 (HPO:0001714) Ventricular hypertrophy 12673660 IBIS 20 / 7739
17
 (HPO:0001638) Cardiomyopathy Frequent [Orphanet] 19684605 IBIS 192 / 7739
18
 (HPO:0001639) Hypertrophic cardiomyopathy 19684605 IBIS 137 / 7739
19
 (HPO:0002119) Ventriculomegaly 12673660 IBIS 253 / 7739
20
 (HPO:0002280) Enlarged cisterna magna 12673660 IBIS 12 / 7739
21
 (HPO:0001642) Pulmonic stenosis 19684605 IBIS 89 / 7739
22
 (HPO:0000824) Growth hormone deficiency Frequent [IBIS] 24124081 IBIS 56 / 7739
23
 (HPO:0001928) Abnormality of coagulation 19684605 IBIS 44 / 7739
24
 (HPO:0002917) Hypomagnesemia 12673660 IBIS 19 / 7739
25
 (HPO:0008947) Infantile muscular hypotonia 12673660 IBIS 482 / 7739
26
 (HPO:0007018) Attention deficit hyperactivity disorder Frequent [IBIS] 24124081; 19684605 IBIS 56 / 7739
27
 (HPO:0001263) Global developmental delay 24124081 IBIS 853 / 7739
28
 (HPO:0001249) Intellectual disability 19684605 IBIS 1089 / 7739
29
 (HPO:0002516) Increased intracranial pressure 12673660 IBIS 47 / 7739
30
 (HPO:0000752) Hyperactivity 12673660 IBIS 140 / 7739
31
 (HPO:0011300) Broad fingertip 12673660 IBIS 2 / 7739
32
 (HPO:0000347) Micrognathia 12673660 IBIS 426 / 7739
33
 (HPO:0000278) Retrognathia 12673660 IBIS 100 / 7739
34
 (HPO:0000268) Dolichocephaly 12673660 IBIS 144 / 7739
35
 (HPO:0000348) High forehead 12673660 IBIS 157 / 7739
36
 (HPO:0000256) Macrocephaly Very frequent [IBIS] 12673660; 19684605 IBIS 298 / 7739
37
 (HPO:0011220) Prominent forehead 12673660 IBIS 137 / 7739
38
 (HPO:0000767) Pectus excavatum Frequent [IBIS] Frequent [Orphanet] 12673660 IBIS 244 / 7739
39
 (HPO:0000470) Short neck 19684605 IBIS 345 / 7739
40
 (HPO:0002650) Scoliosis 12673660 IBIS 705 / 7739
41
 (HPO:0001382) Joint hypermobility 12673660 IBIS 231 / 7739
42
 (HPO:0002750) Delayed skeletal maturation Very frequent [IBIS] Very frequent [Orphanet] 12673660 IBIS 250 / 7739
43
 (HPO:0008070) Sparse hair Very frequent [IBIS] 24124081; 19684605 IBIS 94 / 7739
44
 (HPO:0002162) Low posterior hairline Very frequent [IBIS] Very frequent [Orphanet] 12673660; 19684605 IBIS 88 / 7739
45
 (HPO:0001006) Hypotrichosis Very frequent [Orphanet] 25331583 IBIS 219 / 7739
46
 (HPO:0002217) Slow-growing hair 24124081 IBIS 22 / 7739
47
 (HPO:0002209) Sparse scalp hair 12673660 IBIS 59 / 7739
48
 (HPO:0002020) Gastroesophageal reflux 12673660 IBIS 101 / 7739
49
 (HPO:0002036) Hiatus hernia 12673660 IBIS 24 / 7739
50
 (HPO:0001537) Umbilical hernia 12673660 IBIS 206 / 7739
51
 (HPO:0000035) Abnormality of the testis Occasional [IBIS] Occasional [Orphanet] 19684605 IBIS 296 / 7739
52
 (HPO:0001999) Abnormal facial shape 12673660 IBIS 169 / 7739
53
 (HPO:0002705) High, narrow palate Occasional [Orphanet] 12673660 IBIS 308 / 7739
54
 (HPO:0000422) Abnormality of the nasal bridge 12673660 IBIS 2 / 7739
55
 (HPO:0000463) Anteverted nares Frequent [Orphanet] 12673660 IBIS 305 / 7739
56
 (HPO:0000286) Epicanthus Frequent [IBIS] Frequent [Orphanet] 12673660 IBIS 371 / 7739
57
 (HPO:0000475) Broad neck 12673660 IBIS 12 / 7739
58
 (HPO:0005989) Redundant neck skin 12673660 IBIS 40 / 7739
59
 (HPO:0000465) Webbed neck Frequent [IBIS] Very frequent [Orphanet] 19684605 IBIS 81 / 7739
60
 (HPO:0006610) Wide intermamillary distance 12673660 IBIS 46 / 7739
61
 (HPO:0000357) Abnormal location of ears Very frequent [IBIS] Very frequent [Orphanet] 12673660 IBIS 328 / 7739
62
 (HPO:0000369) Low-set ears 12673660 IBIS 372 / 7739
63
 (HPO:0000358) Posteriorly rotated ears 12673660 IBIS 163 / 7739
64
 (HPO:0000953) Hyperpigmentation of the skin 12673660 IBIS 75 / 7739
65
 (HPO:0000961) Cyanosis 12673660 IBIS 60 / 7739
66
 (HPO:0008064) Ichthyosis rare [HPO:skoehler] 24124081 IBIS 108 / 7739
67
 (HPO:0001047) Atopic dermatitis 12673660 IBIS 20 / 7739
68
 (HPO:0000964) Eczema rare [HPO:skoehler] 24124081 IBIS 81 / 7739
69
 (HPO:0000821) Hypothyroidism 12673660 IBIS 141 / 7739
70
 (HPO:0004414) Abnormality of the pulmonary artery Frequent [Orphanet] 9301585 IBIS 50 / 7739
71
 (HPO:0001510) Growth delay 12673660 IBIS 295 / 7739
72
 (HPO:0008897) Postnatal growth retardation 24124081 IBIS 113 / 7739
73
 (HPO:0030680) Abnormality of cardiovascular system morphology 24124081 IBIS 355 / 7739
74
 (HPO:0002308) Arnold-Chiari malformation 12673660 IBIS 42 / 7739
75
 (HPO:0000238) Hydrocephalus Frequent [IBIS] Frequent [Orphanet] 12673660 IBIS 278 / 7739
76
 (HPO:0040169) Loose anagen hair Very frequent [IBIS] 24124081; 19684605 IBIS 2 / 7739
77
 (HPO:0012758) Neurodevelopmental delay Occasional [Orphanet] 12673660 IBIS 949 / 7739
78
 (OMIM) Darkly pigmented skin 12673660 IBIS 1 / 7739
79
 (OMIM) Mitral/tricuspid valve dysplasia 19684605 IBIS 1 / 7739

Associated genes:

SHOC2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
SHOC2 rs730881020 pathogenic RCV000169685.1

Additional Information:

Clinical Description OMIM Tosti et al. (1991, 1997) reported 2 unrelated children with loose anagen hair in association with Noonan syndrome (see 163950). Mazzanti et al. (2003) restudied these children and described a third unrelated child. All 3 children had short ...
Molecular genetics OMIM Based on a systems biology approach that identified SHOC2 (602775) as a candidate gene, Cordeddu et al. (2009) sequenced SHOC2 coding exons in a Noonan syndrome cohort that included 96 individuals who were negative for mutations in known ...