International CdLS Awareness Day Date in the current year: May 10, 2025

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder with a wide range of features and symptoms caused by a mutation in one of seven different genes: NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4. It is named after the Dutch pediatrician and neuropathologist Cornelia Catharina de Lange, who first described the syndrome in 1933.

CdLS is usually caused by a de novo (spontaneous) mutation that is not inherited from either parent. Signs and symptoms can vary greatly, from mild to severe, depending on the mutation. Some people with CdLS have many of the characteristics associated with the syndrome, while others have only a few. The main features associated with the syndrome include

• Small size and/or weight at birth
• A small head (microcephaly)
• Distinctive facial features (long and/or thick eyebrows, joined eyebrows, long eyelashes, short upturned nose, low set ears, thin downturned lips, high arched palate or cleft palate)
• Intellectual delay and learning disabilities
• Gastrointestinal problems (GERD, feeding difficulties, constipation) and associated slow weight gain
• Behavioral problems: compulsive repetition, self-injury, autistic-like behaviors, anxiety, OCD, ADHD

Secondary features of CdLS include limb abnormalities (small hands and feet, missing fingers or toes, incurved fifth fingers, partially joined toes, etc.), eye problems, hearing loss, communication delays, heart defects, seizures, excess body hair (hirsutism), and musculoskeletal problems.

The exact incidence of CdLS is unclear because the syndrome is rare and underdiagnosed, but it is believed to occur in about one in 10,000 live births. Diagnosis is primarily based on signs and symptoms, but can be confirmed by genetic testing.

There is no cure for CdLS; treatment is based on managing specific symptoms and improving overall well-being and quality of life. Children with CdLS usually require physical therapy, speech therapy, occupational therapy, and special education programs due to delayed growth and intellectual disability.

Treatment may also include a feeding tube or high calorie formula to overcome feeding difficulties, surgery to treat some of the problems (skeletal abnormalities, heart defects, cleft palate, GI problems), psychotherapy for behavioral problems, anticonvulsants for seizures, antidepressants for psychological symptoms, etc.

The prognosis for Cornelia de Lange syndrome depends on the specific symptoms and their severity. Life expectancy for patients is close to normal, but some features, such as heart defects, may reduce it, especially if not treated properly. However, most patients require ongoing medical care throughout their lives.

International CdLS Awareness Day was created to educate the public about Cornelia de Lange syndrome, support patients and their families, advocate for better access to diagnosis and care, and promote research into this rare syndrome.