These diseases present phenotypic overlap including cutaneous features like chilblain lupus, that can be inaugural or present within the first months of life. [hal.archives-ouvertes.fr]

If only one copy of a gene’s pair has the mutation, a person will not present with symptoms of AGS, but will be a carrier of AGS. When two carriers have children together, the odds are one in four that any child they produce will have AGS. [chop.edu]

Most patients with AGS present with progressive microcephaly, spasticity, and cognitive impairment. [onlinelibrary.wiley.com]

• Fever

  When symptoms appear, they may include: Intermittent, unexplained fever Irritability or inconsolable crying Skin problems, including chilblains (rash, lesions, or swelling on fingers, toes and ears that get worse in cold weather) Weak or stiffened muscles [chop.edu]

  […] brain and skin.1 Patients typically exhibit either in utero manifestations resembling an acquired infection,2 or postnatal involvement in infancy, characterized by subacute encephalopathy and loss of acquired skills.3 Children with AGS commonly have fevers [onlinelibrary.wiley.com]

• Crying

  When symptoms appear, they may include: Intermittent, unexplained fever Irritability or inconsolable crying Skin problems, including chilblains (rash, lesions, or swelling on fingers, toes and ears that get worse in cold weather) Weak or stiffened muscles [chop.edu]

  They develop encephalopathy with irritability, persistent crying, abnormal tone, posturing, and an exaggerated startle response. [onlinelibrary.wiley.com]

• Feeding Difficulties

  difficulties A decline in growth of the head Developmental delays Seizures In later-onset AGS, these symptoms may last for several months. [chop.edu]

• Skin Rash

  The symptoms can become more severe over time, and can include smaller head size (microcephaly), liver inflammation, seizures and skin rashes. [chop.edu]

• Irritability

  When symptoms appear, they may include: Intermittent, unexplained fever Irritability or inconsolable crying Skin problems, including chilblains (rash, lesions, or swelling on fingers, toes and ears that get worse in cold weather) Weak or stiffened muscles [chop.edu]

  They develop encephalopathy with irritability, persistent crying, abnormal tone, posturing, and an exaggerated startle response. [onlinelibrary.wiley.com]

• Encephalopathy

  Aicardi-Goutières syndrome: special type early-onset encephalopathy. Eur J Paediatr 2002; 6: A1–A7Google Scholar Aicardi J, Goutières F. [link.springer.com]

  They develop encephalopathy with irritability, persistent crying, abnormal tone, posturing, and an exaggerated startle response. [onlinelibrary.wiley.com]

• Dystonia

  Patients with Aicardi-Goutières syndrome (AGS), the first described of the monogenic interferonopathies, exhibit dystonia, spasticity, developmental delay, intra-cranial calcifications and white matter abnormalities. [theses.fr]

  Over time, severe neurological dysfunction emerges as progressive microcephaly, spasticity, dystonia, and cognitive impairment. [onlinelibrary.wiley.com]

• Quadriplegia

  Manifestations included spastic quadriplegia and anarthria but preserved intellect and increased iron signal in the basal ganglia. [onlinelibrary.wiley.com]

There is no known cure for AGS, but treatment is available to manage symptoms and to help keep children comfortable. Because children with AGS present with different symptoms, the treatment plan for each child is unique. [chop.edu]

Case report The two siblings were enrolled in the National Institutes of Health Undiagnosed Diseases Program under protocol 76‐HG‐0238, ‘Diagnosis and Treatment of Patients with Inborn Errors of Metabolism or Other Genetic Disorders’, approved by the [onlinelibrary.wiley.com]