We get off the train in Amsterdam where we meet

Cornelia de Lange

Cornelia de Lange, first professor of paediatrics (identificatienummer: 100003580 IAV Collection, Atria, The Netherlands).

Cornelia Catharina de Lange was the fifth woman to become a physician in the Netherlands, the fourth woman who earned a doctoral degree. She was an exceptional paediatrician, and a pioneer in clinical genetics. Through clinical observation and neurological studies, she described a new syndrome, known today as Cornelia de Lange syndrome.

The eponymous name is among a total of 105 named after a woman , out of next to thousands  medical eponyms named after men,  according to www.whonamedit.com.

De Lange combined her clinical and scientific work, publishing over 300 papers. She believed in scientific dissemination, addressed to both scientific and general public:

“She became a member of the editorial board of the main Dutch medical journal, Nederlandsch Tijdschrift voor Geneeskunde, and also of the Acta Paediatrica Scandinavica and the Annales Paediatrici. In those journals and also in several other Dutch and foreign journals she described her patients. But she wrote for the layman, too. Her version of a German book on childcare, titled Het Kind, can be considered the Dutch Dr. Spock of the early twentieth century.” (de Knecht-van Eekelen and Hennekam, 1994)

De Lange, starting from detailed clinical observations, was also interested in anatomo-pathological investigation and genetic findings. She had considerable influence on both paediatrics and clinical genetics.

Commitment to public health issues in paediatric care. When Cornelia de Lange graduated, paediatrics was still in its infancy. The Nederlandsche Vereeniging voor Kindergeneeskunde (Dutch Paediatric Society) dates back to 1892. She became president of this society from 1929 to 1935. In 1936 de Lange received the honorary membership of the Dutch Paediatric Society. The first ten years of her career were characterized by a public health commitment, the aim of which was to reduce infant mortality. At the time she wrote several books and brochures for the care of children, intended for a wider audience (note3). As secretary of the Dutch Association for the Protection of Children, she worked for the establishment of consultation offices, which started around 1910.

Unlike her predecessors Aletta Jacobs  and Catharine van Tussenbroek, Cornelia de Lange never supported the work of women in general or that of female doctors in particular in her writing. It is possible that in part because of this attitude she received official recognition in the circle of professional colleagues that other female doctors of similar calibre did not receive. Yet her choice for an unmarried working life placed her at the center of the women’s movement of the time. The women who demonstrated this “rebellion” supported each other and looked for each other. The fact that she gave a lecture at the Dutch National Exhibition of Women’s Work in 1898, the first to be organized by women who aimed at heightening their roles in society, shows that she experienced this feminist demonstration closely. At the same time, Cornelia de Lange held nanny courses, organized by the women’s association ‘Tesselschade’, led by Jeltje de Bosch Kemper.  De Bosch Kemper had hosted the first student association, Dicendo Discente Docemus (DDD), founded by Cornelia de Lange and Jacoba van Maarsseveen, making her home available once a month. The DDD was a female student association which can be seen as a forerunner of the girls’ student societies that began in the Netherlands around 1898.

“As to feminism it is interesting to note that she never openly supported the feminist movement of Aletta Jacobs. In my opinion, this movement was too militant, too radical. That was not her style. She preferred to show by her work that she was equal to men. I suppose that was how she was raised in liberal, well-to-do, patrician family. She did support women students in the “Amsterdamsche Vrouwelijke Studenten Vereeniging” (AVSV, Amsterdam Female Student Association) and women physicians in the “Vereniging van Nederlandse Vrouwelijke Artsen” (VNVA). These women strived for the goal that she herself found important: use your talents to achieve the best for society. That was her motivation to create DDD that should contribute to the scientific development of its members, not just socializing. I think that she left DDD when it became just another women’s club.” (de Knecht-van Eekelen, 2020 personal communication)

When Johanna van Maarseveen died, De Lange wrote obituary in her memory. (original pdf in NTvG, in EN, translation by Jan Johansson)

A formidable clinician. Cornelia de Lange was primarily a clinician. She always underlined careful clinical observation and was very confident in the “vis medicatrix naturae”, as the title of one of her articles says. If there were doubts about the therapy to follow, her advice was always: “Wait and see” or “See, things are going much better, the child has played something today!” She also had an eye for the sick child’s psychosocial environment at a time when many medical colleagues were still under the spell of an active, strictly “rational” approach to medicine based on “pure natural science”. In a sense, Cornelia de Lange made school.

“Her work as a physician is really based on “the clinical eye”. She writes that she preferably sits for a quarter of an hour next to the crib of an infant and just watch the baby. She is against the unnecessary use of laboratory tests. Watch, examine the patient thoroughly and think. Then, you might ask for a laboratory test to confirm your diagnosis. Her 3 volumes titled “Zieke kinderen”, with some 20 case studies in each volume are gems of clinical observation.” (de Knecht-van Eekelen, 2020 personal communication)

The Emma Kinderziekenhuis (Courtesy of Annemarie de Knecht-van Eekelen)

After the end of her chair, she led the so-called “Saturday afternoon club”, where the experience was exchanged with colleagues and former students where they lectured on recent developments in paediatrics. When she worked at Emma Children Hospital, de Lange began to focus more on scientific work, which was very varied. She published on nutritional disorders, blood abnormalities, childhood tuberculosis and numerous special observations. Subsequently, her research focused more and more on the pathology of the central nervous system in young children and infants.

“The first sign of de Lange’s interest in neurology inclined topics was a publication on neuropathy in 1905, followed by publications in 1912 on acute cerebral tremor and an overview article on literature about spasms and paralyses with whooping cough in 1912. She published articles on congenital spinal paralyses (1920), total and partial lack of the corpus callosum (1924), histopathology of the spinal cord with congenital syphilis (also in 1924), microcephalie (1925) and congenital anomalies of the urinary tract (with Schippers in 1927).” (van Drenth and Baas, 2016)

In 1927, she was the first woman in the Netherlands to be appointed full professor of paediatrics at the University of Amsterdam. In addition to these professional activities, Cornelia de Lange has also developed other activities for the medical profession.

de Lange C. (1933): Sur un type nouveau de degenciration (typus Amstelodamensis). Arch Med Enfants 36:713-719.

Cornelia de Lange syndrome (CdLS). In 1933, she described a hereditary and congenital complex of malformations that causes motor and intellectual disabilities. In short succession, she saw two children with these symptoms. In 1933, Cornelia de Lange published an article based on her observations of two girls with anomalies in the French review “Archives des Médicine”. De Lange was unable to identify similar cases in a thorough bibliographic search, which implied that she presented them as a new entity, called “typus Amstelodamensis”. In reality though, in 1916, Dresden’s medical assistant Winfried Brachmann (1888-1969) published his findings on the case of a boy brought to hospital six days after his birth. The boy died, however, on the nineteen-day from malnutrition. The child had significant malformations and Brachmann indicated the most conspicuous anomaly as ” Monodactyl due to ulnar defect, with Flight skin formation in the elbows “. In addition, the child was very young and showed excessive? hair growth. His facial features were also abnormal, especially the widening of the forehead. As Brachmann concluded in his article, the tendency for variations or anomalies in this individual was unmistakable. Since Brachmann was called to military action in the First World War, his research on the specific condition of the boy was stopped. In December 1932, Cornelia de Lange saw for the first time a “typus Amstelodamensis” child, a girl of 17 months. She was mainly affected by facial aspects of the child:

“Cheveux long, assez clairsemés, bruns, sourcils noirs très marqués se rencontrant dans la ligne médiane, cils extrêmement longs. Oreilles non déformées, mais placées un peu bas. Nez effilé, narines en avant, mandibule peu développée et en conséquence menton petit. Visage pale, mais teinte bleuâtre autour des yeux, du nez et de la bouche. Veines dilatées dans régions temporales. Voûte palatine un peu ogivale. Pas encore de dents.” (de Lange, 1933)

[TRANSLATE “Long hair, rather sparse, brown, very marked black eyebrows meeting in the midline, extremely long eyelashes. Ears not deformed, but placed a little low. Tapered nose, nostrils forward, mandible poorly developed and consequently small chin. Pale face, but bluish tint around the eyes, nose and mouth. Dilated veins in temporal regions. Hard palate a little ogival. No teeth yet.”]

Subsequently, de Lange described the malformations of the limbs,

“Mains et pieds petits et potelés, doigts et orteils courts, petit doigt incurvé vers l’annulaire. Pouce et éminence thénar dans une position plus proximale que d’ordinaire, donnât ainsi à la main une certaine ressemblance avec le pied de l’orang et du chimpanzé. ”(de Lange, 1933)

[TRANSLATE “Small, chubby hands and feet, short fingers of both hands and feet, little finger curved towards the ring finger. Thumb and ball of the thumb in a position more proximal than usual, thus gave the hand a certain resemblance to the foot of the orang and the chimpanzee.”]

De Lange conducted microscopic research on blood and urine and took X-rays too. She described an anomaly of the skull, to which she referred as brachycephaly. She described the somatic and behavioural phenotype to define a “mental development disease”. At the time she based this diagnosis simply on behavioural observations without verification through psychological evaluation, which could have indicated the degree of intellectual disability. Two months after the first girl’s description, another girl was hospitalized with pneumonia. The similarity between the first and this second girl was so striking that the nurses thought the first girl had returned:

“Ces enfants se ressemblaient à un degré tel, que les infirmières qui avaient soigné la première petite malade s’écrièrent: «Voilà W.E. de retour! », mais, réfléchissant un moment, elles ajoutèrent. « Non, ce n’est pas possible, cette enfant est plus jeune que W.E. » ”

[TRANSLATE: “These children were so alike that the nurses who had cared for the first sick girl exclaimed: “Here is W.E. back! But, thinking for a moment, they added. “No, it is not possible, this child is younger than W.E.”]

After carefully observing the girl, De Lange concluded that the second girl showed the same characteristics as the first one. Since the two children weren’t related, she supposed she was dealing with two isolated cases. De Lange was of the opinion that the condition was caused by genetic abnormalities. In order to promote knowledge of the phenomenon she stressed that new cases had to be found for further examination of the syndrome. In 1938, De Lange published a second paper reporting a clinical series of five cases: a third girl with the same features and two cases published by Vedder. In addition to performing neurological and radiographic examination, De Lange also collected the data from the autopsy performed on one of the first two girls she observed, and reported the results of the macroscopic and microscopic examination of the cerebral hemispheres. This child died at five years and nine months in an asylum. No abnormalities were found in the organs of the chest and endocrine system. The peritoneum, however, had shown anomalies that are common among mammals, but not among humans. In addition, microscopic tests of the right hemisphere had revealed a reduced number of brain wraps. Again, De Lange was aware that further studies were needed to unravel the underlying pathological anatomy of the identified condition. However, with both her articles, in 1933 and 1938, De Lange described a new rare condition called “typus Amstelodamensis”. In her discovery, her meticulous observations of the specific phenotypic abnormalities had been crucial. Furthermore, her research in the anatomo-pathological abnormalities was supportive in unveiling the first knowledge of the endo-phenotype of these clinical cases.

To date, a few reports of brain findings in Cornelia de Lange Syndrome have been published. Neuroimaging or autopsy findings show some localized or diffuse brain abnormalities: hypoplastic corpus callosum and cerebellar vermis, mild dilatation of the ventricles system, reduction in size of the pituitary gland (Avagliano et al., 2017).

The PhD ceremony of Ida Loemongga Haroen, first woman from Indonesia to get a PhD (1932) (Courtesy of Annemarie de Knecht-van Eekelen)

Biography. Cornelia Catharina de Lange was born on June 24, 1871, in Alkmaar, by Catharina Jacoba Luchtmans (1843-1919), belonging to the Luchtmans family, founder of one of the oldest publishing houses in the Netherlands, and Adrianus Petrus de Lange (1843-1897), lawyer and member of the Alkmaar city council. Cornelia de Lange showed an inclination to study from an early age. After completing her HBS (Dutch technical school with a high school diploma), she wanted to study medicine. However, her father wanted to give her an adequate female education and sent her to Zurich for a year, hoping that she would abandon the idea to continuing studies during a stay abroad. On the contrary Cornelia remained with her intention: in 1891 she studied for a semester chemistry, which was considered less detestable for a woman by the Dutch society than the study of medicine and since 1892 she studied medicine.

She graduated in 1897 and in the same year obtained her doctorate with the gynaecologist H. Treub. The doctoral topic was related to the problem which the first paediatricians were facing: the artificial feeding of children and the fight against frequent fatal nutritional disorders.

the portrait made by Lizzy Ansingh. It was donated by the AVSV on November 6, 1957, to the University of Amsterdam.(Courtesy of Annemarie de Knecht-van Eekelen)

Her circle of friends included some Amsterdam intellectuals – as Lizzy Ansingh (1875-1959) who would later paint her academic portrait – and the first Dutch housing inspector Johanna ter Meulen (1867-1937), who became her life partner and with whom she later lived in the De Bosch Kemper house.

After her doctorate, Cornelia de Lange settled as a general practitioner in Amsterdam, which at the time meant only one thing for a woman: a doctor for women and children. It is possible that Cornelia de Lange adapted her wishes to the possibilities, the fact is that she wanted to specialize as a paediatrician. She left for the second time for Zurich, where she practiced under supervision of Oskar Wyss (1840-1918). Back in Holland, in 1907, she was appointed pediatrician to the Emma Children’s Hospital in Amsterdam, where she was in charge of the baby room. In 1927, Cornelia de Lange’s pioneering work finally received its recognition: she was appointed Professor of Paediatrics.

Her lecture when she became professor.(Courtesy of Annemarie de Knecht-van Eekelen)

“Her appointment to the chair of paediatrics in 1927 was quite an event. In her inaugural address, titled Het werk, dat om wacht (“The work that is awaiting us”), she outlined the fields of interest that should be studied during the years to come. The main topics were the treatment of encephalitis, hydrocephalus, convulsions, and tuberculosis; the problems of nervous children; pathological anatomy; and genetics.” (de Knecht-van Eekelen and Hennekam, 1994)

After some hesitation, she accepted the chair of paediatrics at the University of Amsterdam, a position that she voluntarily resigned eleven years later, at the age of 67 years. This made her the first female professor in a medical faculty in the Netherlands. After her resignation as a professor, De Lange returned to the Emma Children’s Hospital. During the World War II, she served as the superintendent of the hospital. It was a tough time:

“The cold winter of 1944-1945 was an especially dramatic experience. The hospital was filled with children dying from exhaustion, malnutrition, and diarrhea. It took great effort to obtain food for the patients and fuel for the stoves. Professor de Lange became very ill, but she came through and enjoyed the liberation by the Allied Forces.” (de Knecht-van Eekelen and Hennekam, 1994)

The last publication of her hand was published three months before her death (Amsterdam, January 29, 1950), at the age of 78.

“On January 29, Professor Cornelia de Lange died at the age of 79, after a long life entirely devoted to pediatrics. The history of her life and work is that of a medical woman, who took her profession and scientific work as a vocation, with deeply felt gratitude and awe for the inherent privilege to come into more intimate contact with the wisdom of Nature. […] For us, her pupils, her work and personality have been inspiring until the very end of her life and her death is a very hard loss; all we can do is to continue work in the way she expected us to do.” (Middelhoven, 1950)

Prizes and awards.

  • 1927 honorary membership of the AVSV (Amsterdam Female Student Association), when she got her professorship
  • 1929-1935, president of the Dutch Paediatric Society
  • 1936 the honorary membership of the Dutch Paediatric Society
  • 1947, on the occasion of her 50th jubilee as physician, she got a royal distinction: “Ridder in de Orde van de Nederlandsche Leeuw”.

The entry in the PhD registry with the wrong name (Courtesy of Annemarie de Knecht-van Eekelen)

Trivia

  • Please note that her name by birth is Cornelia Catherina de Lange. There is a mistake in the PhD document that writes Catherine.
  • 1946 At the occasion of her 75th birthday, the editor of the Annales Paediatrica, Ernst Freudenberg, underlined her professional prestige by stating: ‘In this specialty she belongs beyond any dispute to the first authorities within the field.’
  • 1946 for her 75th birthday, the NTvG journal published a special “Cornelia de Lange number”:

“From the Cornelia de Lange issue of the Nederlandsch Tijdschrift voor Geneeskunde it is clear how loved she was and that she created her school of paediatricians. Several young women had followed her example and had chosen to become a paediatrician. The issue contains contributions by Prof. Bernard Brouwer (1881-1949, with whom she performed many neurological studies), and his wife, her colleague paediatrician Hélène Brouwer-Frommann. There was a posthumously article by her friend, the paediatrician Jan Cornelis Schippers (1881-1946), one of those who had taken the initiative for this issue. Then there were contributions by the Amsterdam paediatricians […] By colleagues […], and her pupils Anna Schoo (pediatrician in Alkmaar), Tieline Janssen (paediatrician) and H. Reerink (paediatrician in Arnhem).” (de Knecht-van Eekelen, 1990)

Cornelia de Lange medal. Since 1985, the Dutch Child Neurology Society awards an honorary medal in the name of Cornelia de Lange to a particularly accredited researcher. The first Cornelia de Lange medal went to the French paediatric neurologist and epileptologist Jean Aicardi.

“The medal is a design by Prof. E. Claus of the State Academy for Visual Art in Amsterdam. The portrait of Cornelia de Lange is chosen because she was the first in the Netherlands who had a profound interest in childhood neurological disorders.” (Ned Tijdschr Geneeskd. 1986;130:182.)”

In 1981, the Cornelia de Lange Syndrome Foundation was founded in the U.S.A. to provide information to parents and doctors. 

Acknowledgements

We are grateful to Annemarie de Knecht-van Eekelen for providing material and sharing her information and for her kind support.

Credit

To cite this profile, please use the following format:

Mele, S. and Metitieri, T. (2020). Profile of Cornelia de Lange. In WiNEu, European Women in Neuroscience, Untold stories: The Women Pioneers of Neuroscience in Europe. Retrieved from https://wineurope.eu/de-lange/

Selected work

For a complete list, see the monograph “Cornelia Catharina de Lange (1871-1950)” by A. de Knecht-van Eekelen (Nijmegen: Nederlandse Vereniging voor Kinderneurologie. 1990).

  • de Lange C. (1933): Sur un type nouveau de degenciration (typus Amstelodamensis). Arch Med Enfants 36:713-719.
  • de Lange C. (1936): A contribution to the pathology of identical twins. Arch Dis Child ll:39-48.
  • de Langc C (1937): Two cases of congenital anomalies of the brains. Am J Dis Child 53:429-444.
  • de Lange C. (1938): Nouvelle observation du ‘typus amstelodamensis’ et examen anatomo-pathologique de ce type. Arch Med Enfants 41:193-203.

References

  • Avagliano L., Grazioli P., Mariani M., Bulfamante G.P., Selicorni A., Massa V. (2017). Integrating molecular and structural findings: Wnt as a possible actor in shaping cognitive impairment in Cornelia de Lange syndrome. Orphanet J Rare Dis;12(1):174.
  • de Knecht-van Eekelen A. (1990). Cornelia Catharina de Lange (1871-1950). Nijmegen: Nederlandse Vereniging voor Kinderneurologie.
  • de Knecht-van Eekelen A., Hennekam RC. (1994). Historical study: Cornelia C. de Lange (1871-1950)–a pioneer in clinical genetics. Am J Med Genet. Sep 1;52(3):257-66.
  • Middelhoven A. (1950). Professor Cornelia de Lange in memoriam. Acta Paediatr. 1950;39(3):177-8.
  • van Gijn J. and  Gijselhart J.P.(2011). Cornelia de Lange (1871-1950) en haar syndroom. Ned Tijdschr Geneeskd. 2011;155:A2355
  • van Drenth A. and Baas D., (2016). Anomalous children and eponymous fame. The discovery of the first ‘typus Amstelodamensis’ girls by the Dutch pediatrician Cornelia de Lange (1871-1950) in the 1930s. pdf