Hypogonadotropic hypogonadism 21 with or without anosmia, also known as HH21, is a disorder characterized by absent or incomplete sexual maturation by the age of 18, low levels of circulating gonadotropins (LH and FSH), and sometimes, anosmia (loss of smell).

Key Features:

• Absent or incomplete sexual maturation by age 18 [5]
• Low levels of circulating gonadotropins (LH and FSH) [5][6]
• Sometimes associated with anosmia (loss of smell) [7]

Causes: HH21 is caused by a mutation in the FLRT3 gene on chromosome 20p11 [7][8]. This genetic mutation leads to the development of hypogonadotropic hypogonadism, which is characterized by low levels of gonadotropins and impaired sexual maturation.

Other Information: The heritability of HH21 is not well established, and there is limited information available on its causal genes [8]. However, research suggests that mutations in the FLRT3 gene are a significant contributor to the development of this disorder.

Hypogonadotropic hypogonadism-21 (HH21) is a disorder characterized by partial or absent puberty in individuals with anosmia, which is the loss of sense of smell. This condition can also be associated with small testicular volumes in men and primary amenorrhea in women.

Common Signs and Symptoms:

• Partial or absent puberty
• Anosmia (loss of sense of smell)
• Small testicular volumes in men
• Primary amenorrhea in women
• Low bone mass has been reported in some patients

Additional Features:

• Delayed or incomplete sexual maturation
• Incomplete development of secondary sexual characteristics
• Decreased muscle mass and body hair growth in males
• Lack of growth and sexual development at the standard age for puberty in children

Genetic Associations: HH21 can be caused by heterozygous mutations in the FLRT3 gene on chromosome 20p11, sometimes in association with mutations in other genes such as FGFR1, HS6ST1, and FGF17.

It's essential to note that each individual may experience a unique set of symptoms, and not everyone will exhibit all of these characteristics. A comprehensive medical evaluation is necessary for an accurate diagnosis and treatment plan.

References: * [Miraoui et al., 2013] reported low bone mass in some patients with HH21. * [1] described partial or absent puberty in anosmic patients. * [5] mentioned small testicular volumes in men and primary amenorrhea in women. * [12] discussed the genetic associations of HH21, including mutations in the FLRT3 gene.

Diagnostic Tests for Hypogonadotropic Hypogonadism 21 (HH21) with or without Anosmia

Hypogonadotropic hypogonadism 21 (HH21) is a disorder characterized by partial or absent puberty in anosmic patients, associated with small testicular volumes in men and primary amenorrhea in women. The diagnostic tests for HH21 involve evaluating hormone levels and the sense of smell.

• Hormone Evaluation: This includes measuring sex steroids, gonadal peptides, and pituitary gonadotropin dosage to assess the level of hypogonadism.
• Evaluation of the Sense of Smell: Since anosmia is a characteristic feature of HH21, evaluating the sense of smell can help confirm the diagnosis. This can be done through olfactory testing or other methods.

Additional Diagnostic Methods

Other diagnostic methods that may be used to diagnose hypogonadotropic hypogonadism 21 with or without anosmia include:

• Genetic Testing: Genetic testing for mutations in the FLRT3 gene, which is associated with HH21.
• Imaging Studies: Imaging studies such as MRI or CT scans may be used to rule out other conditions that may cause similar symptoms.

References

• [10] From OMIM: Hypogonadotropic hypogonadism-21 (HH21) is characterized by partial or absent puberty in anosmic patients, in association with small testicular volumes in men and primary amenorrhea in women.
• [9] Diagnostic methods consist of hormone evaluation (sex steroids, gonadal peptides and pituitary gonadotropin dosage), as well as evaluation of the sense of smell.
• [13] A number sign (#) is used with this entry because hypogonadotropic hypogonadism-21 with or without anosmia (HH21) can be caused by heterozygous mutation in the FLRT3 (604808) gene on chromosome 20p11.

Treatment Options for Hypogonadotropic Hypogonadism 21

Hypogonadotropic hypogonadism 21, also known as Kallmann syndrome, is a rare genetic disorder characterized by delayed or absent puberty and low levels of sex hormones. The treatment options for this condition focus on replacing the deficient hormones to induce puberty and maintain normal hormone levels.

• Pulsatile GnRH therapy: This treatment involves administering gonadotropin-releasing hormone (GnRH) in a pulsatile manner, which helps stimulate the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This approach has been shown to be effective in inducing puberty and restoring normal hormone levels in most patients [3].
• Gonadotropin regimens: In some cases, gonadotropins such as human menopausal gonadotropin (hMG) or recombinant FSH may be used to stimulate ovulation or sperm production. However, this approach is typically reserved for individuals who have not responded to pulsatile GnRH therapy [3].
• Hormone replacement therapy: For individuals with hypogonadotropic hypogonadism 21, hormone replacement therapy (HRT) may be necessary to maintain normal hormone levels and prevent complications such as osteoporosis or cardiovascular disease. HRT typically involves administering estrogen and progesterone in women, while testosterone is used in men [9].

It's essential to note that treatment options for hypogonadotropic hypogonadism 21 with or without anosmia are highly individualized and may vary depending on the specific genetic mutation responsible for the condition. A healthcare professional should be consulted to determine the most effective treatment plan.

References:

[3] by J Young · 2019 · Cited by 342 — Finally, fertility can be induced with pulsatile GnRH treatment or gonadotropin regimens in most patients. [9] A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and ...

Differential Diagnosis of Hypogonadotropic Hypogonadism 21 (HH21)

Hypogonadotropic hypogonadism 21 (HH21) is a condition characterized by partial or absent puberty in individuals, often associated with small testicular volumes in males. When HH21 is accompanied by anosmia (loss of smell), it is termed Kallmann syndrome. However, the differential diagnosis of HH21 can be challenging due to its variable clinical features.

Differential Diagnosis

The main and most difficult differential diagnosis of congenital hypogonadotropic hypogonadism in boys is constitutional delay of growth and puberty (CDGP) [3]. Patients with CDGP may exhibit similar symptoms, such as delayed puberty, small testicular volumes, and normal or slightly low levels of gonadotropins.

Other Differential Diagnoses

• Kallmann Syndrome: When HH21 is accompanied by anosmia, it is termed Kallmann syndrome [4]. However, not all individuals with Kallmann syndrome have anosmia; some may exhibit symptoms without olfactory impairment.
• Gonadotropin Deficiency: Subjects with gonadotropin deficiency and anosmia may have affected relatives without anosmia, demonstrating that the clinical features are variable [6].
• Isolated Hypogonadotropic Hypogonadism: This condition is characterized by low serum levels of testosterone in male individuals (usually <2 nmol/l) in the absence of anosmia or other symptoms [9].

Key Points

• HH21 can be challenging to diagnose due to its variable clinical features.
• Constitutional delay of growth and puberty (CDGP) is a common differential diagnosis for congenital hypogonadotropic hypogonadism in boys.
• Kallmann syndrome, gonadotropin deficiency, and isolated hypogonadotropic hypogonadism are other conditions that may be considered in the differential diagnosis of HH21.

References

[1] Congenital hypogonadotropic hypogonadism-21 (HH21) is characterized by partial or absent puberty in anosmic patients, in association with small testicular volumes in men [2].

[3] The main and most difficult differential diagnosis of congenital IHH in boys is constitutional delay of growth and puberty. Patients with CDGP may exhibit similar symptoms, such as delayed puberty, small testicular volumes, and normal or slightly low levels of gonadotropins.

[4] Kallmann syndrome (KS) is a developmental genetic disorder characterized by the association of congenital hypogonadotropic hypogonadism (CHH) due to GnRH deficiency [5].

[6] Subjects with gonadotropin deficiency and anosmia may have affected relatives without anosmia, thus demonstrating that the clinical features are variable.

[9] Isolated hypogonadotropic hypogonadism is characterized by low serum levels of testosterone in male individuals (usually <2 nmol/l) in the absence of anosmia or other symptoms.