(1997) must be present:
Total or partial agenesis of the corpus callosum
Minor craniofacial anomalies such as macrocephaly or hypertelorism
Moderate to severe psychomotor retardation with hypotonia
PolydactylyThe differential diagnosis includes Greig cephalopolysyndactyly syndrome, orofaciodigital syndrome types I and II, Meckel–Gruber syndrome, Smith–Lemli–Opitz syndrome, Rubinstein–Taybi syndrome, Cockayne syndrome, Aicardi syndrome, Neu–Laxova syndrome, Young–Madders syndrome, oto-palato-digital syndrome type 2, Toriello–Carey syndrome, and Da Silva syndromes. ACLS may be differentiated from Greig cephalopolysyndactyly syndrome by the presence of intracranial cysts.ACLS may be suspected antenatally if a previous child is affected, as any subsequent child has a 25% chance of having ACLS. Obstetric ultrasonography or magnetic resonance imaging can reveal polydactyly and/or cerebral malformations from the 20th week of gestation. Chorionic villus sampling and molecular genetic testing can be performed to confirm whether mutations in disease-associated genes are present.ACLS is an extremely rare disorder, with 34 cases described in the literature as of 2005. Management
Management of ACLS consists mainly of monitoring by a pediatric neuropsychiatrist and supportive therapies or accommodations such as occupational therapy and special education plans. Surgery may be considered in early childhood to remove extra digits in case of polydactyly or resolve orofacial defects such as cleft palate. If present, seizures and renal parenchymal hypertension may be treated with anticonvulsants and antihypertensive drugs, respectively. Patients may be offered genetic and vocational counselling when appropriate. Prognosis
Lifespan may range from stillbirth to normal expectancy depending on severity of hypotonia and onset of epilepsy.
Further out into the fibrous shell there is a zone that contains T cells and plasma cells in association with blood vessels. The histology of pulmonary nodules are similar to that of subcutaneous nodules, with central necrosis surrounded by palisading macrophages and inflammatory infiltrate. Risk Factors
Rheumatoid nodules develop if a person currently has rheumatoid arthritis. However, not all people with rheumatoid arthritis develop rheumatoid nodules. Some risk factors for rheumatoid nodules for people with rheumatoid arthritis may include:
Smoking (strong association)
Elevated levels of serum rheumatoid factors
HLA-DRB1 gene (weak association)
Trauma to small vessels
Having severe rheumatoid arthritis
Taking Methotrexate over other arthritis drugs

Diagnosis
Differential diagnosis of rheumatoid nodules can be classified from localization, depth pathology, age of onset, persistence, rheumatoid factor, concomitant joint disease, and bone erosions. Diagnosis is typically determined clinically by a rheumatologist. Rheumatoid arthritis associated rheumatoid nodules are typically subcutaneous and occur at extensor sites. The onset typically starts in adulthood and presents with rheumatoid factors and bone erosions, and concomitant joint diseases. The pathology is characterized by central necrosis, palisading mononuclear cells, and perivascular lymphocytic infiltrations.Rheumatoid nodulosis is characterized by multiple subcutaneous nodules presenting with rheumatoid factors but an absence of joint complaints. The nodules are typically small and concentrated on the extensor sites of the hands and feet, sometimes accompanied by bone erosions. The onset typically starts in adulthood with a pathology similar to rheumatoid arthritis associated rheumatoid nodules.Benign rheumatoid nodules are often not associated with rheumatoid factors or concomitant joint diseases. They are typically found on the feet, scalp, and pretibial regions.