“A Syndrome of Infantilism, Congenital Webbed Neck, and Cubitus Valgus” (1938), by Henry Hubert Turner

In 1938, physician Henry Hubert Turner published “A Syndrome of Infantilism, Congenital Webbed Neck, and Cubitus Valgus,” hereafter “A Syndrome of Infantilism,” in the journal Endocrinology, in which he described a condition that researchers later named Turner syndrome. Turner syndrome is a genetic condition that affects biological females, characterized by a partially or completely missing X chromosome. In the paper, Turner describes a previously unrecognized set of symptoms in seven different females, including a lack of physical and sexual development, infertility, webbed neck, and elbow deformities, among others. Turner also records various methods of hormone treatments for his patients, such as growth hormone and estrogen injections. “A Syndrome of Infantilism” was one of the first published descriptions of Turner syndrome, a developmental condition that affects one in 2,500 live female births globally, and highlighted the use of hormone treatments to promote the development of stunted physical and sexual growth.

1. Background and Context
2. Article Roadmap
3. Detailed Content
4. Legacy and Impact

Background and Context

Turner syndrome involves an alteration in the genetic material of females, specifically the X sex chromosome. Almost all organisms’ cells contain chromosomes made up of DNA, which codes for the proteins that help build the body’s traits and functions. Humans typically have a total of forty-six chromosomes in almost all cells. Each of those chromosomes pairs up making a total of twenty-three pairs of chromosomes. One of those pairs of chromosomes are the sex chromosomes, which can influence the development of sexual characteristics such as genitals. There are two types of sex chromosomes, referred to as X and Y. People with one X and one Y chromosome typically develop as biologically male, while people with two X chromosomes typically develop as biologically female. However, when someone is missing a sex chromosome, issues in development can arise, like a lack of maturation in the sex organs.

A missing or partially missing X chromosome results in numerous cardiac, reproductive, and growth-related symptoms. Those symptoms often include a lack of development of the female reproductive organs often resulting in infertility, heart defects that are present from birth, and a webbed neck, which is an extension of skin from the neck to the shoulders. People with Turner syndrome also have lower levels of naturally occurring growth hormones, which results in slower physical growth and smaller stature. Growth hormones are chemicals in the body that promote growth in almost every tissue and organ. Many individuals with Turner syndrome also have a hormone deficiency in the female sex hormone estrogen, which can result in weak or brittle bones.

At the time of publication of “A Syndrome of Infantilism,” Turner worked as Chief of the Adult Metabolic Clinic at University Hospital in Oklahoma City, Oklahoma. He was a physician who studied endocrinology, which is the study of the endocrine glands and hormones, which are chemical signals secreted by glands that circulate throughout the body and regulate the body’s various functions. From 1924 to 1949, Turner worked in many positions at the University of Oklahoma College of Medicine, or OU College of Medicine, and worked his way up to Clinical Professor of Medicine, and eventually to Professor Emeritus of Medicine. He published roughly thirty papers during his lifetime and focused on a variety of endocrinological issues, such as male infertility and diabetes insipidus, a hormonal condition in which the body cannot retain fluid. From 1932 to 1937, Turner examined seven female patients with symptoms related to physical and sexual underdevelopment, then published his findings in “A Syndrome of Infantilism.”

According to Turner, at the time of writing “A Syndrome of Infantilism,” there were no papers written on the syndrome that Turner described, however, Turner referred to the works of other researchers to try to find commonalities between the symptoms he observed in his seven patients. To address the physical characteristics of the webbed neck, Turner referenced the work of Oskar Kobyliński, who was a medical student at the University in Dorpat, Russia, and one of the first to describe the webbed neck, in 1882. Turner derived the term “webbed neck” from Kobyliński. Turner also looked for an explanation of the webbed neck in the work of Maurice Klippel, who researched the nervous system and mental disorders, and Andre Feil, who researched birth defects in France during the early 1900s. Klippel and Feil observed the fused bones in the neck of a patient in 1912, a symptom they characterized as Klippel-Feil syndrome. Klippel-Feil syndrome is a rare disorder characterized by the fusion of bones in the neck, resulting in a short neck. Another physician that Turner refers to was someone he calls Funke, a surgeon from Germany, who had a patient with pterygium colli, which is another name for webbed neck and stunted sexual and physical growth. However, Turner’s patients did not match the descriptions that Funke, Kobyliński, or Klippel and Feil provided. Thus, he characterized the symptoms he observed as a new disorder.

Article Roadmap

“A Syndrome of Infantilism” consists of three main sections. In the untitled first section, Turner compares the symptoms he observed to other conditions displaying similar symptoms to demonstrate that he believes he discovered a new syndrome. The second section, “Case Report,” contains seven subsections, one for each of his patients. Each subsection provides a full health report of each patient, their symptoms, and reactions to various hormone treatments. The last section, “Summary,” is where Turner gives an overview of his patients’ common symptoms of stunted physical and sexual growth, elbow deformities, and webbed neck, and states that gonadotropic hormone treatments produced the most physical and sexual development in his patients, compared to growth and estrogen hormone treatments.

Detailed Content

In the first section, a brief introduction to his observations, Turner describes how he has not seen the symptoms of webbed neck, elbow deformities, and lack of physical and sexual growth together in any previous researchers’ work. However, Turner states that it is not uncommon for the symptoms that he observed to occur independently of one another. He refers to the work of Klippel and Feil to distinguish between their syndrome and the symptoms of his patients. The symptoms of Klippel-Feil are short or absent neck, lowered hairline on the neck, asymmetrical facial features, and a curved spine or other deformities resulting in difficulties with breathing or swallowing. Turner states that the short neck that he witnesses in his patients is due to the webbing of the neck, not due to any fusion of bones in the neck or spine. Turner’s patients display a short hairline, but there are no other symptoms that relate to any other neck deformities. He finally refers to Funke and reports that Funke did not describe the bone deformities that Turner studied in his patients. Turner states that despite the similar symptoms seen in other conditions, the combination of symptoms in his study is novel and to his knowledge never been categorized together before.

In the “Case Report” section of the article, Turner provides an in-depth account of the common physical symptoms that were present in his seven patients, whom he refers to as Cases 1 through 7, such as stunted growth, webbed neck, and elbow deformities. The patients’ ages ranged from fifteen years old to twenty-three years old. All seven patients’ height and weight were below average for their sex and age range. Turner notes that for Case 5, her small stature resulted in her associates treating her like a child and her parents fearing that she may never get married. Turner notes that all patients exhibited webbed necks, except for Case 4, who had a shorter neck with a wide base. Due to the webbed neck, Turner reports that all patients except Case 4 had very low hairlines on the back of their necks. Turner also reports that all seven patients showed defining feature of cubitus valgus, which is a deformity that results in an increased carrying angle of the elbow. Increased carrying angle is when the arms rest palms up at the sides of the body. The deformed angle of the elbow causes the forearms and hands to stick out and away from the body. The increased carrying angle can also be a precursor to damage to the nerve that runs from the arm to the fingers. Turner includes X-rays of three different increased carrying angles on the last page of his paper.

In the “Case Report” section, Turner also notes some physical symptoms that his seven patients did not all share, such as hair growth, skin color changes, and eye conditions. Despite a lack of body hair, he records that Case 3 had an abundance of hair growth on the forearms. Case 3 also showed an uncommon symptom of acrocyanosis on her hands and feet, which is a bluish tint that can appear on body parts experiencing a decrease in oxygen. Neither hypertrichosis nor acrocyanosis causes any detrimental health issues. Another symptom Turner reports is that only Case 1 and Case 3 presented with a squint of the right eye, which means the eye points in different directions and cannot focus on one thing. If left untreated, eye squints can result in a permanent decrease in vision and cause social and psychological issues.     

Turner continues in the “Case Report” section to describe that he had gynecological examinations done on all seven patients to investigate the lack of development of their external genitalia. The external genitalia all fall under the term vulva, which forms an oval-like shape if viewed from the front. The vulva consists of various skin folds, and the large outermost one is the labia majora. The inner skin fold after the labia majora is smaller and called the labia minora. Turner had his colleague J. B. Eskridge, who studied gynecology at OU School of Medicine, perform the gynecological examinations. Most of the patients had an underdeveloped labia majora and minora, as well as a lack of pubic hair. Turner reports that almost all his patients had a significantly small labia majora and minora. The function of the labia majora and minora is to protect the inner workings of the vulva, such as the vaginal opening, and to stop the vagina from getting dry.

Continuing the gynecological examination, Eskridge found that there was a lack of development of the vagina in almost all the patients. The vagina is a canal with an opening in the middle of the vulva toward the bottom if viewed from a front view. Eskridge relayed that he could not measure or examine many of the patients’ vaginas, as they were far too small. Eskridge was only able to measure the vaginal size of Case 1, who had a vagina size of 1.6 inches. According to a paper from 2006, the typical vagina is around 2.4 inches deep. An underdeveloped vagina can result in the process of sexual intercourse being difficult and painful.

The gynecological exam in the “Case Report” section also addresses the lack of development of the internal genitalia such as the uterus and the adnexa. The uterus is a larger pear-shaped organ, that is typically three by two by one inch in size. The adnexa is a region containing the fallopian tubes, ovaries, and ligaments that hold the uterus in place. Two fallopian tubes connect the uterus to the ovaries, and there is one fallopian tube on either side of the uterus. The uterus and adnexa development varied amongst the seven patients. For patients with underdeveloped adnexa, Eskridge typically could not examine many of the patients’ uteruses and adnexa, as some of the uteruses were barely present. However, for Case 5, her uterus was comparatively the size of a six- or seven-year-old’s uterus. The patients also had underdeveloped cervixes, and Turner compares them to the size of a pea. The cervix is also a part of the internal genitalia and is a small circular structure located towards the end of the vagina forming a small channel-like structure leading to the uterus. The average size of a cervix is almost one inch in length. Due to the underdevelopment of the uterus and the cervix and the absence of the adnexa, which are all organs involved in housing a developing fetus and eventually delivering it, childbirth would be impossible for Turner’s patients. The underdevelopment in the organs involved in reproduction thus results in infertility for people with Turner syndrome.

Turner also had full body X-rays done on all seven patients and, in the “Case Report” section, reports that he found common symptoms of delayed bone development in the finger bones and weakening in some of the bones of the patients. At the time of the article’s publication in 1938, X-rays could provide images of the different bones, though the skin tissue often obscured the bone. A common symptom Turner notes in most of his patients’ X-rays was that they had a delay in the growth of the epiphyseal plates in the finger bones, which are regions in the bones where bone growth occurs. Turner provides three X-ray figures of the underdeveloped hand bones at the bottom of the article. Turner’s X-rays also found that six of his patients showed some form of demineralization in their bones. Demineralization is when the bones in the body lose minerals, and in many cases can cause osteoporosis, a decrease in bone density or mass that results in brittle bones. Despite the demineralization and underdevelopment of epiphyseal plates, Turner states that most of the bone scans showed no other bone abnormalities.

Turner did report finding differences in the X-rays of Cases 4 and 6, who had other bones with stunted epiphyseal plate growth. For example, Turner found that along with the delayed growth in the finger bones for Case 4, there was also a delay in the growth of the epiphyseal plates in her forearm bones. Turner describes Case 6 as having growth disturbances and could not determine if it was a nutritional or endocrine problem. The forearm bones in the patient were smaller than the typical size, and the heads of those bones had different shapes. The smaller right forearm bone did not have growth from the epiphyseal plate, and the left forearm bones had a flat and higher-density epiphyseal plate. The growth of the epiphyseal plate is critical for growth in stature, as well as for preventing fractures that could cause permanent damage to the growth of that bone.

The final part of the “Case Report” section describes the different hormone treatments Turner tried on three of his patients, including growth hormone injections, which he found were not very effective in facilitating the physical growth of his patients. Turner tried growth hormone-based injections on Cases 1, 2, and 3, who all displayed stunted physical and sexual growth. Turner documents that Case 1 and Case 3 showed very minimal growth in height, averaging no greater than two inches more than their original height. Turner describes that Cases 1 and 2 also showed some pubic hair growth. He also found that Case 2 especially showed a moistening of the inner linings of the vagina. However, Turner maintains that the growth hormone-based injections were not very effective in increasing the height and weight of the patients.

Turner also tried various gonadotropic hormone-based injections in Case 1 and Case 2, which was effective in facilitating sexual development. Gonadotropin-releasing hormones, or GnRH, help regulate reproduction in the female body, as they trigger the release of gonadotropin hormones that, in a typical female’s case, maintain puberty, sexual development, and the release of eggs from the ovaries. With a lack of GnRH, chances of infertility in people with Turner syndrome is higher. Turner reports that in both patients he treated with GnRH, there was a great increase in cervix size, vagina depth, and pubic hair, and the vagina had a moist inner lining. He also reports a growth in the size of the labia majora for Case 2. Thus, Turner concludes that the gonadotropic hormone-based injections were effective in increasing in the size of the internal and external genitalia.

The final hormone treatment Turner tried was estrogen-based hormone injections on one patient, Case 1, which he claims was slightly effective in stimulating sexual development. Estrogen hormones are sex hormones released from the ovary that help stimulate the development of female sex characteristics such as breasts. Turner only provided the estrogen-based hormone injections to Case 1, who was especially lacking developed sexual characteristics. He administered the estrogen injections along with the gonadotropic hormone-based injections and found that it continued to increase pubic hair and produced a slight increase in weight. Turner states that the size of the uterus increased from not being visible to being the size of a pecan. The glandular tissues in the breast started to grow and were finally visible. After the combined treatment, Turner attempted just the estrogen-based hormone injections, which resulted in a typical menstrual flow for three days and small growth in the size of the labia minora and majora, cervix, uterus, and the glandular tissues in the breast. Turner found that the combination of GnRH with estrogen hormones stimulated the development of the uterus and glandular tissue. However, estrogen by itself resulted only in a small growth of the sex organs. According to Turner, when using just estrogen instead of the GnRH, the vagina of Case 1 shrank in length from 3.5 inches to 2.4 inches.

The final section titled “Summary” is where Turner summarizes his observations of his seven patients and concludes that the gonadotropin hormones promoted sexual development most effectively compared to other hormone treatments. Turner reiterates that, to his knowledge, no researchers had ever categorized symptoms of stunted physical and sexual growth resulting in infertility, webbed neck, and cubitus valgus together as a singular syndrome. He argues that the symptoms of various other conditions could not compare to the symptoms displayed by his patients. As for Turner’s hormone treatments, he states that the GnRH treatments showed a clear increase in genital development, as opposed to other treatments that were less effective.

Legacy and Impact

As of 2024, “A Syndrome of Infantilism” has been cited a total of 1,599 times and has led other researchers to further describe and discover the causes of Turner syndrome. Following the publication of  “A Syndrome of Infantilism,” researchers investigated the cause of the syndrome. In 1959, Charles Edmund Ford, a researcher who studied chromosomes in England, and his colleagues found the chromosomal cause of Turner syndrome. They published an article titled “A Sex Chromosome Anomaly in a Case of Gonadal Dysgenesis (Turner Syndrome),” which found that a missing X chromosome was responsible for the symptoms of a patient with Turner syndrome. Then, in 1996, a researcher and physician from the US named Paul Saenger published an article called “Turner’s Syndrome,” which discusses the syndrome’s symptoms and its management. He discusses how to manage symptoms with age and the possible learning difficulties that people with Turner syndrome can have such as issues with visuospatial organization, which are tasks like driving, or nonverbal problem-solving assignments like math. Saenger suggests that people with Turner syndrome should be screened for learning difficulties so they receive appropriate care. Finally, he cites “A Syndrome of Infantilism” as one of the first articles describing the symptoms of Turner syndrome.

As of 2024, researchers continue to define Turner syndrome by the main symptoms Turner described, however, researchers have also discovered additional symptoms associated with the condition. In 2022, a group of researchers from Denmark and the Netherlands published their article, “The Changing Face of Turner Syndrome,” in which they cite “A Syndrome of Infantilism” to explain that the symptoms and genetic developments associated with Turner Syndrome require a multidisciplinary clinical treatment approach. The authors describe new symptoms that Turner did not describe in his 1938 paper such as heart defects and ear infections. The researchers further described the three main symptoms Turner observed, including cubitus valgus, webbed neck, and stunted physical and sexual growth resulting in infertility, which remain the defining characteristics of the syndrome. The authors also incorporate more modern technology to explain the gene interactions that lead to the display of certain symptoms, such as cubitus valgus.

As of 2024, there are many organizations that provide support to individuals with Turner Syndrome, such as The Turner Syndrome Society of the United States and interACT. Turner syndrome is a condition that many are not aware of but is one of the most common genetic conditions someone can be born with. The Turner Syndrome Society of the United States focus on spreading information on what Turner syndrome is, providing support groups or connections for individuals with the syndrome, and raising donations to continue research into the complexities of Turner syndrome. The organization also frequently holds events to provide resources on Turner syndrome and raise the self-esteem of people who need it. Another organization called interACT focuses on preventing the forced surgical treatment of intersex people, including removing or changing intersex traits through procedures like genital surgeries, while patients are at an age too young to give consent. InterACT uses the term intersex broadly to encompass people who have atypical sex characteristics or sex organs. InterACT refers to Turner syndrome as an intersex condition. However, many physicians often do not use the term intersex to describe Turner syndrome, and instead use disorders of sex development, or DSD, for diagnosis. Some people who refer to themselves as intersex find the label DSD inaccurate, though, as it implies that something about their bodies needs to be fixed. Elizabeth Reis, an author and professor of gender studies at the University of Oregon in Corvallis, Oregon, suggests using the term divergence of sex development instead of disorders of sex development to avoid perpetuating stigma. Additionally, not all people with Turner syndrome consider themselves intersex. Many of them prefer to just be understood as female, as that is the sex their anatomy primarily aligns with.

As of 2024, all over the world, Turner syndrome affects one in 2,000 to one in 2,500 female births and the most common treatments for Turner Syndrome are still growth hormone and estrogen hormone treatments. The hormone treatments provide some solutions to stunted growth and weak bones. However, Turner syndrome’s large number of symptoms often go untreated due to the need for different medical specialties to address them. For example, heart disease is a common symptom of Turner syndrome and requires medical care from a heart specialist rather than an endocrinologist who many administer hormone treatments. The authors of “The Changing Face of Turner Syndrome” also suggest that the creation of multispecialty clinics would address the many different symptoms that come with Turner syndrome.  

“A Syndrome of Infantilism” introduced a new syndrome defined by its developmental issues. Turner’s work was one of the first to clearly define Turner syndrome as a new condition or syndrome. His paper accelerated research into the syndrome, allowing researchers to understand the biological cause, and as of 2024 to have a better understanding of the condition, especially from a genetic perspective.