# Síndrome Williams

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

## Identificadores

- **ORPHA**: 904 — https://www.orpha.net/en/disease/detail/904
- **CID-10**: Q93.8
- **OMIM**: OMIM:194050 — https://omim.org/entry/194050

## Descrição clínica

Uma doença neurológica multissistémica genética rara, caracterizada por uma aparência facial distinta, anomalias cardíacas (mais frequentemente estenose aórtica supravalvular), anomalias cognitivas e do desenvolvimento e anomalias do tecido conjuntivo (por exemplo, hipermobilidade articular). O dismorfismo facial caracteriza-se por testa larga, estreitamento bitemporal, plenitude periorbitária, padrão de íris estrelado e/ou rendilhado, nariz curto e arrebitado com ponta bulbosa, filtro longo, boca larga, lábios carnudos e micrognatia ligeira.

## Epidemiologia e herança

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

## Sinais e sintomas (234 fenótipos HPO)

- **Hipodontia** — HPO: HP:0000668 (Frequente (79-30%))
- **Herança autossômica dominante** — HPO: HP:0000006
- **Achatamento malar** — HPO: HP:0000272 (Ocasional (29-5%))
- **Estenose da artéria renal** — HPO: HP:0001920 (Ocasional (29-5%))
- **Pele macia** — HPO: HP:0000977 (Frequente (79-30%))
- **Bochechas cheias** — HPO: HP:0000293 (Frequente (79-30%))
- **Doença celíaca** — HPO: HP:0002608 (Ocasional (29-5%))
- **Comportamento atípico** — HPO: HP:0000708 (Frequente (79-30%))
- **Ponte nasal deprimida** — HPO: HP:0005280 (Frequente (79-30%))
- **Cifoescoliose** — HPO: HP:0002751 (Frequente (79-30%))
- **Envelhecimento prematuro dos cabelos** — HPO: HP:0002216 (Frequente (79-30%))
- **Plenitude periorbital** — HPO: HP:0000629 (Frequente (79-30%))
- **Cutis laxa** — HPO: HP:0000973 (Frequente (79-30%))
- **Déficit de atenção** — HPO: HP:0000736 (Frequente (79-30%))
- **Dificuldades alimentares na infância** — HPO: HP:0008872 (Frequente (79-30%))
- **Lóbulo da orelha grande** — HPO: HP:0009748 (Frequente (79-30%))
- **Retardo do crescimento intrauterino** — HPO: HP:0001511
- **Intolerância à glicose** — HPO: HP:0001952
- **Malformação de Chiari tipo I** — HPO: HP:0007099
- **Retrusão médio-facial** — HPO: HP:0011800
- **Incoordenação** — HPO: HP:0002311 (Frequência: 15/20)
- **Hipotonia generalizada** — HPO: HP:0001290
- **Hipotelorismo** — HPO: HP:0000601 (Ocasional (29-5%))
- **Micropênis** — HPO: HP:0000054 (Ocasional (29-5%))
- **Unha pequena** — HPO: HP:0001792 (Frequente (79-30%))
- **Morte súbita** — HPO: HP:0001699 (Raro (<5%))
- **Otite média recorrente** — HPO: HP:0000403 (Frequente (79-30%))
- **Cognição construtiva visuoespacial prejudicada** — HPO: HP:0010794 (Frequente (79-30%))
- **Maturação sexual precoce** — HPO: HP:0100000
- **Traço obsessivo-compulsivo** — HPO: HP:0008770
- **Anormalidade da refração** — HPO: HP:0000539 (Ocasional (29-5%))
- **Paralisia das cordas vocais** — HPO: HP:0001605 (Ocasional (29-5%))
- **Hipoplasia cerebelar** — HPO: HP:0001321
- **Alargamento medial da sobrancelha** — HPO: HP:0010747 (Frequente (79-30%))
- **Ponta nasal larga** — HPO: HP:0000455 (Frequente (79-30%))
- **Testa estreita** — HPO: HP:0000341 (Frequente (79-30%))
- **Estenose da artéria coronária** — HPO: HP:0005145 (Frequente (79-30%))
- **Hipertensão portal** — HPO: HP:0001409 (Ocasional (29-5%))
- **Boca aberta** — HPO: HP:0000194 (Frequente (79-30%))
- **Anormalidade do sono** — HPO: HP:0002360 (Ocasional (29-5%))
- _...e mais 194 sintomas. Ver https://raras.org/doenca/sindrome-williams._

## Genes associados (19)

- **GTF2I** — General transcription factor II-I [Role in the phenotype of]
  - Função: Interacts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes. Promotes the
- **MLXIPL** [MENDELIAN]
  - Função: Glucose-responsive transcription activator that regulates fatty acid synthesis and glycolysis. Key determinant of systemic insulin sensitivity and glucose homeostasis. Important for the expression of
- **TMEM270** — Transmembrane protein 270 [Role in the phenotype of]
- **RFC2** — Replication factor C subunit 2 [Candidate gene tested in]
  - Função: Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating
- **EIF4H** — Eukaryotic translation initiation factor 4H [Role in the phenotype of]
  - Função: Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA
- **LIMK1** — LIM domain kinase 1 [Role in the phenotype of]
  - Função: Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, P
- **STX1A** — Syntaxin-1A [Role in the phenotype of]
  - Função: Plays an essential role in hormone and neurotransmitter calcium-dependent exocytosis and endocytosis (PubMed:26635000). Part of the SNARE (Soluble NSF Attachment Receptor) complex composed of SNAP25,
- **GTF2IRD2** — General transcription factor II-I repeat domain-containing protein 2A [Role in the phenotype of]
- **ELN** — Elastin [Role in the phenotype of]
  - Função: Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial
- **GTF2IRD1** — General transcription factor II-I repeat domain-containing protein 1 [Role in the phenotype of]
  - Função: May be a transcription regulator involved in cell-cycle progression and skeletal muscle differentiation. May repress GTF2I transcriptional functions, by preventing its nuclear residency, or by inhibit
- **FKBP6** — Inactive peptidyl-prolyl cis-trans isomerase FKBP6 [Role in the phenotype of]
  - Função: Has an essential role in spermatogenesis (PubMed:36150389). It is required to repress transposable elements and prevent their mobilization, which is essential for the germline integrity (By similarity
- **NCF1** — Neutrophil cytosol factor 1 [Role in the phenotype of]
  - Função: Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:2547247, PubMed:2550933, PubMed:383557
- **VPS37D** — Vacuolar protein sorting-associated protein 37D [Role in the phenotype of]
  - Função: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth an
- **BAZ1B** — Tyrosine-protein kinase BAZ1B [Role in the phenotype of]
  - Função: Atypical tyrosine-protein kinase that plays a central role in chromatin remodeling and acts as a transcription regulator (PubMed:19092802). Involved in DNA damage response by phosphorylating 'Tyr-142'
- **CLIP2** — CAP-Gly domain-containing linker protein 2 [Role in the phenotype of]
  - Função: Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operat

## Medicamentos em desenvolvimento (1)

- CLEMASTINE — Fase Phase 3 (Histamine H1 receptor antagonist)
- Fonte: https://platform.opentargets.org/disease/MONDO_0008678

## Ensaios clínicos ativos (13)

- **NCT02706639** [RECRUITING]: Williams Syndrome (WS) and Supravalvar Aortic Stenosis (SVAS) DNA and Tissue Bank — https://clinicaltrials.gov/study/NCT02706639
- **NCT01132885** [RECRUITING]: Defining the Brain Phenotype of Children With Williams Syndrome — https://clinicaltrials.gov/study/NCT01132885
- **NCT07493096** [RECRUITING]: Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders — https://clinicaltrials.gov/study/NCT07493096
- **NCT00768820** [RECRUITING]: The Psychiatric and Cognitive Phenotypes in Velocardiofacial Syndrome — https://clinicaltrials.gov/study/NCT00768820
- **NCT06740162** [RECRUITING]: Physical Activity and Community EmPOWERment Project — https://clinicaltrials.gov/study/NCT06740162
- **NCT07285720** [RECRUITING]: Phonological Constraints on Language Development in Individuals With Williams Syndrome — https://clinicaltrials.gov/study/NCT07285720
- **NCT01793168** [RECRUITING]: Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford — https://clinicaltrials.gov/study/NCT01793168
- **NCT06930417** [RECRUITING]: Characterization and Natural History of Williams Syndrome and Other Chromosome 7q11.23 Variants — https://clinicaltrials.gov/study/NCT06930417
- **NCT04463316** [RECRUITING]: GROWing Up With Rare GENEtic Syndromes — https://clinicaltrials.gov/study/NCT04463316
- **NCT03836300** [ENROLLING_BY_INVITATION]: Parent and Infant Inter(X)Action Intervention (PIXI) — https://clinicaltrials.gov/study/NCT03836300

## 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)

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- [Monossomia parcial do braço curto do cromossomo 1](https://raras.org/doenca/monossomia-parcial-do-braco-curto-do-cromossomo-1) — ORPHA:261857 — 57 sintomas em comum
- [Síndrome cardio-facio-cutâneo](https://raras.org/doenca/sindrome-cardio-facio-cutaneo) — ORPHA:1340 — 54 sintomas em comum
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- [Trissomia parcial do braço curto do cromossomo 16](https://raras.org/doenca/trissomia-parcial-do-braco-curto-do-cromossomo-16) — ORPHA:262794 — 52 sintomas em comum
- [Monossomia parcial do cromossomo 19](https://raras.org/doenca/monossomia-parcial-do-cromossomo-19) — ORPHA:261841 — 52 sintomas em comum
- [Trissomia parcial do cromossomo 16](https://raras.org/doenca/trissomia-parcial-do-cromossomo-16) — ORPHA:262672 — 52 sintomas em comum
- [Síndrome ADNP](https://raras.org/doenca/sindrome-adnp) — ORPHA:404448 — 51 sintomas em comum
- [Duplicação/triplicação parcial do cromossomo 5](https://raras.org/doenca/duplicacaotriplicacao-parcial-do-cromossomo-5) — ORPHA:262211 — 51 sintomas em comum
- [Doença do neurodesenvolvimento CTCF-relacionada](https://raras.org/doenca/doenca-do-neurodesenvolvimento-ctcf-relacionada) — ORPHA:363611 — 51 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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