# Síndrome Noonan

> Página oficial: https://raras.org/doenca/sindrome-noonan
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 648 — https://www.orpha.net/en/disease/detail/648
- **CID-10**: Q87.1
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A síndrome de Noonan (NS) é caracterizada por baixa estatura, dismorfismos faciais típicos e defeitos cardíacos congénitos.

## Epidemiologia e herança

- **Prevalência**: 1-5 / 10 000
- **Padrão de herança**: Autosomal dominant, Autosomal recessive

## Sinais e sintomas (267 fenótipos HPO)

- **Nistagmo** — HPO: HP:0000639 (Ocasional (29-5%))
- **Ponte nasal hipoplásica** — HPO: HP:0005281
- **Pregas plantares profundas** — HPO: HP:0001869
- **Bossas frontais** — HPO: HP:0002007
- **Malformação de Dandy-Walker** — HPO: HP:0001305
- **Escafocefalia** — HPO: HP:0030799
- **Sinostose unilambdoide esquerda** — HPO: HP:0011321
- **Nariz curto** — HPO: HP:0003196
- **Prolapso da valva tricúspide** — HPO: HP:0001704
- **Pele redundante** — HPO: HP:0001582
- **Malformação de Chiari tipo I** — HPO: HP:0007099
- **Craniossinostose sagital** — HPO: HP:0004442
- **Anormalidade do queixo** — HPO: HP:0000306
- **Resposta de deglutição orofaríngea prejudicada** — HPO: HP:0031162
- **Alimentação por sonda nasogástrica na infância** — HPO: HP:0011470
- **Melanoma lentigo maligno** — HPO: HP:0012059
- **Morfologia anormal do esôfago** — HPO: HP:0002031
- **Sucção pobre** — HPO: HP:0002033
- **Disfagia** — HPO: HP:0002015
- **Lóbulo da orelha grande** — HPO: HP:0009748
- **Comprometimento cognitivo** — HPO: HP:0100543
- **Espessamento palpebral** — HPO: HP:0030939
- **Numerosos nevos** — HPO: HP:0001054
- **Estenose do canal espinhal** — HPO: HP:0003416
- **Dermatite atópica** — HPO: HP:0001047
- **Ventriculomegalia** — HPO: HP:0002119
- **Atraso global leve do desenvolvimento** — HPO: HP:0011342
- **Hemangioma glabellar** — HPO: HP:0001076
- **Trombocitopenia amegacariocítica** — HPO: HP:0004859
- **Infertilidade masculina** — HPO: HP:0003251
- **Neurofibrossarcoma** — HPO: HP:0100697
- **Quilotórax** — HPO: HP:0010310
- **Cifoescoliose** — HPO: HP:0002751
- **Sinovite** — HPO: HP:0100769
- **Desvio radial do dedo** — HPO: HP:0009466
- **Pectus carinatum superior** — HPO: HP:0000917
- **Atividade reduzida do fator XII** — HPO: HP:0004841
- **Hipogonadismo** — HPO: HP:0000135
- **Deficiência auditiva** — HPO: HP:0000365
- **Déficit de crescimento na infância** — HPO: HP:0001531
- _...e mais 227 sintomas. Ver https://raras.org/doenca/sindrome-noonan._

## Genes associados (17)

- **MRAS** — Ras-related protein M-Ras [Disease-causing germline mutation(s) in]
  - Função: Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival (PubMed:16630891, PubMed:28289718, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670
- **LRRC56** — Leucine-rich repeat-containing protein 56 [Disease-causing germline mutation(s) in]
  - Função: Required for the assembly of dynein arms
- **MAPK1** — Mitogen-activated protein kinase 1 [Disease-causing germline mutation(s) in]
  - Função: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK casca
- **CBL** — E3 ubiquitin-protein ligase CBL [Disease-causing germline mutation(s) in]
  - Função: E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, PubMe
- **LZTR1** — Leucine-zipper-like transcriptional regulator 1 [Disease-causing germline mutation(s) in]
  - Função: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates ubiquitination of Ras (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS) (PubMed:30442762, PubMed:30442766, P
- **RASA2** — Ras GTPase-activating protein 2 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4)
- **RIT1** — B-cell lymphoma/leukemia 11B [Disease-causing germline mutation(s) (gain of function) in]
  - Função: Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic sign
- **KRAS** — GTPase KRas [Disease-causing germline mutation(s) in]
  - Função: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:20949621, PubMed:39809765). Plays an important role in the regulation of cell proliferation (PubMed:22711838, PubMed:23698361).
- **RAF1** — RAF proto-oncogene serine/threonine-protein kinase [Disease-causing germline mutation(s) (gain of function) in]
  - Função: Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining
- **NRAS** — GTPase NRas [Disease-causing germline mutation(s) in]
  - Função: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
- **SOS1** — Son of sevenless homolog 1 [Disease-causing germline mutation(s) (gain of function) in]
  - Função: Promotes the exchange of Ras-bound GDP by GTP (PubMed:8493579). Probably by promoting Ras activation, regulates phosphorylation of MAP kinase MAPK3/ERK1 in response to EGF (PubMed:17339331). Catalytic
- **RRAS2** — Ras-related protein R-Ras2 [Disease-causing germline mutation(s) in]
  - Função: GTP-binding protein with GTPase activity, involved in the regulation of MAPK signaling pathway and thereby controlling multiple cellular processes (PubMed:31130282, PubMed:31130285, PubMed:39809765).
- **SOS2** — Son of sevenless homolog 2 [Disease-causing germline mutation(s) in]
  - Função: Acts as guanine nucleotide exchange factor (GEF) for RAS proteins. Catalyzes the GDP-to-GTP exchange, resulting in an increase of the active GTP-bound form of HRAS (PubMed:20639119). Acts as a key mod
- **BRAF** — Serine/threonine-protein kinase B-raf [Disease-causing germline mutation(s) in]
  - Função: Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathw
- **PTPN11** — Tyrosine-protein phosphatase non-receptor type 11 [Disease-causing germline mutation(s) in]
  - Função: Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:10655584, PubMed:14739280, PubMed:18

## Medicamentos em desenvolvimento (3)

- SOMATROPIN — Fase Phase 3 (Growth hormone receptor agonist)
- SIMVASTATIN — Fase Phase 3 (HMG-CoA reductase inhibitor)
- MECASERMIN — Fase Phase 2 (Insulin-like growth factor I receptor agonist)
- Fonte: https://platform.opentargets.org/disease/MONDO_0018997

## Ensaios clínicos ativos (18)

- **NCT05202210** [RECRUITING]: Constitution of a Biological Collection to Study the Pathophysiology in Noonan Syndrome — https://clinicaltrials.gov/study/NCT05202210
- **NCT07464821** [RECRUITING]: National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype — https://clinicaltrials.gov/study/NCT07464821
- **NCT04888936** [RECRUITING]: Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies — https://clinicaltrials.gov/study/NCT04888936
- **NCT06668805** [RECRUITING]: A Basket Study of Vosoritide in Children With Turner Syndrome, Short Stature Homeobox-Containing Gene Deficiency, and Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment — https://clinicaltrials.gov/study/NCT06668805
- **NCT05361811** [RECRUITING]: Acceptance and Commitment Therapy for Caregivers of Children With a RASopathy: An Internal Pilot Feasibility Study and Follow-up Randomized Controlled Trial — https://clinicaltrials.gov/study/NCT05361811
- **NCT03050268** [RECRUITING]: Familial Investigations of Childhood Cancer Predisposition — https://clinicaltrials.gov/study/NCT03050268
- **NCT07336394** [RECRUITING]: Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques — https://clinicaltrials.gov/study/NCT07336394
- **NCT06147414** [RECRUITING]: Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders — https://clinicaltrials.gov/study/NCT06147414
- **NCT04395495** [RECRUITING]: RASopathy Biorepository — https://clinicaltrials.gov/study/NCT04395495
- **NCT06555237** [RECRUITING]: MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies — https://clinicaltrials.gov/study/NCT06555237

## Centros de referência no Brasil (24)

- Hospital Universitário Prof. Edgard Santos (HUPES) (Salvador/BA)
- Hospital Infantil Albert Sabin (Fortaleza/CE)
- Hospital de Apoio de Brasília (HAB) (Brasília/DF)
- Hospital Estadual Infantil e Maternidade Alzir Bernardino Alves (HIABA) (Vila Velha/ES)
- Hospital das Clínicas da UFG (Goiânia/GO)
- Hospital Universitário da UFJF (Juiz de Fora/MG)
- Hospital das Clínicas da UFMG (Belo Horizonte/MG)
- Hospital Universitário Julio Müller (HUJM) (Cuiabá/MT)
- Hospital Universitário João de Barros Barreto (Belém/PA)
- Hospital Universitário Lauro Wanderley (HULW) (João Pessoa/PB)
- Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) (Recife/PE)
- Hospital Pequeno Príncipe (Curitiba/PR)
- Hospital Universitário Regional de Maringá (HUM) (Maringá/PR)
- Hospital de Clínicas da UFPR (Curitiba/PR)
- Hospital Universitário Pedro Ernesto (HUPE-UERJ) (Rio de Janeiro/RJ)
- Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/Fiocruz) (Rio de Janeiro/RJ)
- Hospital São Lucas da PUCRS (Porto Alegre/RS)
- Hospital de Clínicas de Porto Alegre (HCPA) (Porto Alegre/RS)
- Hospital Universitário da UFSC (HU-UFSC) (Florianópolis/SC)
- Hospital das Clínicas da FMUSP (São Paulo/SP)

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome cardio-facio-cutâneo](https://raras.org/doenca/sindrome-cardio-facio-cutaneo) — ORPHA:1340 — 98 sintomas em comum
- [Síndrome do cabelo em fase anágena](https://raras.org/doenca/168) — ORPHA:168 — 82 sintomas em comum
- [Síndrome Noonan-like com cabelo em fase anágena solto](https://raras.org/doenca/sindrome-noonan-like-com-cabelo-em-fase-anagena-solto) — ORPHA:2701 — 82 sintomas em comum
- [Síndrome de blefarofimose-perturbação do desenvolvimento intelectual](https://raras.org/doenca/sindrome-de-blefarofimose-perturbacao-do-desenvolvimento-intelectual) — ORPHA:293642 — 80 sintomas em comum
- [Monossomia parcial do cromossomo 19](https://raras.org/doenca/monossomia-parcial-do-cromossomo-19) — ORPHA:261841 — 79 sintomas em comum
- [Monossomia parcial do braço curto do cromossomo 1](https://raras.org/doenca/monossomia-parcial-do-braco-curto-do-cromossomo-1) — ORPHA:261857 — 74 sintomas em comum
- [Monossomia parcial do cromossomo 3](https://raras.org/doenca/monossomia-parcial-do-cromossomo-3) — ORPHA:261776 — 72 sintomas em comum
- [Síndrome aneuploidia variada em mosaico](https://raras.org/doenca/sindrome-aneuploidia-variada-em-mosaico) — ORPHA:1052 — 71 sintomas em comum
- [Deleção parcial do braço longo do cromossomo 10](https://raras.org/doenca/delecao-parcial-do-braco-longo-do-cromossomo-10) — ORPHA:262083 — 70 sintomas em comum
- [Síndrome de perturbação do desenvolvimento intelectual-apneia do sono obstrutiva-dismorfia ligeira AHDC1-relacionada](https://raras.org/doenca/sindrome-de-perturbacao-do-desenvolvimento-intelectual-apneia-do-sono-obstrutiva-dismorfia-ligeira-ahdc1-relacionada) — ORPHA:412069 — 69 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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