Michels Caskey syndrome

Overview

Michels Caskey syndrome, also referred to as Persistent Müllerian Duct Syndrome (PMDS), is a rare genetic condition affecting individuals with a 46,XY karyotype (genetically male) who present with persistent Müllerian structures such as a uterus and fallopian tubes, structures typically found in females. Despite having normal male external genitalia and secondary sexual characteristics, affected individuals retain internal female reproductive organs. The condition was extensively studied by Drs. Michels and Caskey, who helped define its clinical and pathological features, hence the eponymous name.

PMDS is a form of male pseudohermaphroditism and is usually discovered incidentally during surgeries for undescended testes (cryptorchidism) or inguinal hernia repairs. The presence of Müllerian structures does not typically affect external male genital development, which can lead to delayed diagnosis until adolescence or adulthood.

Causes

The primary cause of Michels Caskey syndrome (PMDS) is a defect in the anti-Müllerian hormone (AMH) pathway. AMH, produced by Sertoli cells in the testes during fetal development, is responsible for the regression of the Müllerian ducts. In PMDS, this regression fails due to one of the following reasons:

• Mutations in the AMH gene: Leading to insufficient or non-functional anti-Müllerian hormone.

• Mutations in the AMHR2 gene: Affecting the receptor for AMH, rendering the body unresponsive to the hormone.

Both types of mutations follow an autosomal recessive inheritance pattern, meaning a child must inherit two copies of the defective gene (one from each parent) to be affected. Carriers of a single mutated gene typically show no symptoms.

Symptoms

The symptoms of Michels Caskey syndrome are often subtle and may go unnoticed until complications arise. Key clinical features include:

• Normal male external genitalia

• Undescended testes (cryptorchidism), unilateral or bilateral

• Inguinal hernia (often containing uterine or fallopian tissue)

• Presence of uterus, fallopian tubes, and upper vagina on imaging or during surgery

In many cases, the condition is discovered during surgical exploration for undescended testes or hernia repair. Rarely, infertility in adulthood may prompt investigations that reveal underlying PMDS.

Diagnosis

Diagnosis of Michels Caskey syndrome involves a combination of clinical evaluation, imaging, hormone testing, and genetic analysis. Common diagnostic steps include:

• Ultrasound or MRI: To visualize the presence of Müllerian structures (uterus, fallopian tubes)

• Laparoscopy: Allows direct observation and is often done during surgery for undescended testes

• Hormonal studies: May show normal male testosterone levels with persistent AMH levels in early life

• Karyotype analysis: Confirms 46,XY genetic male status

• Genetic testing: Identifies mutations in the AMH or AMHR2 genes

Early diagnosis is beneficial for timely management and prevention of potential complications such as infertility or malignancy.

Treatment

Treatment for Michels Caskey syndrome is primarily surgical and tailored to the individual's presentation and future fertility considerations. Management may include:

• Orchiopexy: Surgical relocation of undescended testes into the scrotum to reduce cancer risk and preserve fertility

• Removal of Müllerian structures: In cases where they pose a risk of obstruction, malignancy, or interfere with testicular descent

• Fertility evaluation and support: Especially important in adulthood if infertility becomes a concern

• Hormonal therapy: Not usually required as testosterone levels are typically normal

• Psychological counseling: May be offered depending on the timing of diagnosis and patient concerns regarding identity or reproductive health

Multidisciplinary care involving pediatric surgeons, endocrinologists, geneticists, and urologists is often recommended for optimal management.

Prognosis

The prognosis of individuals with Michels Caskey syndrome depends on timely diagnosis and management of associated anomalies. If undescended testes are surgically corrected early, the risk of infertility and testicular cancer can be minimized. Some individuals may still face reduced fertility or subfertility despite treatment.

The presence of Müllerian structures typically does not cause functional problems, but their surgical removal may be considered to prevent complications. Overall, individuals with isolated PMDS and proper medical care can lead healthy, normal lives with preserved male identity and function.