Kallmann syndrome 1

Other Names: KAL1; Kallmann syndrome, X-linked; Kallmann syndrome, type 1, X-linked

• Kallmann syndrome 1 is an inherited disorder characterized by delayed or absent puberty and an impaired sense of smell.
• This disorder is a form of hypogonadotropic hypogonadism.
• Affected males are usually born with a small penis and undescended testicles.
• Affected females usually do not begin menstruating at puberty and have little or no breast development.
• Kallmann syndrome 1 is the most common type of Kallmann syndrome (there are four types identified at this time).

Cause

It is caused by mutations in the KAL1 gene.

Inheritance

X-linked recessive inheritance

It is inherited in an X-linked recessive fashion.

Signs and symptoms

The features of Kallmann syndrome 1 vary, even among affected people in the same family. The condition is characterized by delayed or absent puberty and an impaired sense of smell. It is a form of hypogonadotropic hypogonadism, which is a condition affecting the production of hormones that direct sexual development. Males with hypogonadotropic hypogonadism are often born with an unusually small penis and undescended testes. At puberty, most affected individuals do not develop secondary sex characteristics, such as the growth of facial hair and deepening of the voice in males. Affected females usually do not begin menstruating at puberty and have little or no breast development. In some people, puberty is incomplete or delayed.

In Kallmann syndrome 1, the sense of smell is either diminished or completely absent. This feature distinguishes Kallmann syndrome from most other forms of hypogonadotropic hypogonadism, which do not affect the sense of smell. Many people with Kallmann syndrome are not aware that they are unable to detect odors until the impairment is discovered through testing.

Additional signs and symptoms can include a failure of one kidney to develop, a cleft lip or palate, abnormal eye movements, hearing loss, and abnormalities of tooth development. Some affected individuals have a condition called bimanual synkinesis, in which the movements of one hand are mirrored by the other hand.

Location of hypothalamus, pituitary gland and olfactory bulb

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Anosmia(Lost smell)
• Anterior hypopituitarism
• Decreased fertility(Abnormal fertility)
• Decreased testicular size(Small testes)
• Delayed puberty(Delayed pubertal development)
• Erectile dysfunction(Abnormal erection)
• Hypogonadotropic hypogonadism
• Hyposmia
• Hypothalamic gonadotropin-releasing hormone deficiency
• Micropenis(Short penis)

Disruption of the hormonal pathways

30%-79% of people have these symptoms

• Abnormality of the voice(Voice abnormality)
• Breast hypoplasia(Underdeveloped breasts)
• Cryptorchidism(Undescended testes)
• Reduced bone mineral density(Low solidness and mass of the bones)

5%-29% of people have these symptoms

• Abnormal morphology of female internal genitalia
• Abnormality of cardiovascular system morphology
• Ataxia
• Bimanual synkinesia(Hand mirror movements)
• Cleft palate(Cleft roof of mouth)
• Color vision defect(Abnormal color vision)
• Delayed skeletal maturation(Delayed bone maturation)
• Dysarthria(Difficulty articulating speech)
• Dyspareunia
• Facial asymmetry(Asymmetry of face)
• Gait disturbance(Abnormal gait)
• Gynecomastia(Enlarged male breast)
• Ichthyosis
• Muscle weakness(Muscular weakness)
• Muscular hypotonia(Low or weak muscle tone)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Obesity(Having too much body fat)
• Paraplegia(Leg paralysis)
• Pes cavus(High-arched foot)
• Pes planus(Flat feet)
• Primary amenorrhea
• Ptosis(Drooping upper eyelid)
• Recurrent fractures(Increased fracture rate)
• Reduced number of teeth(Decreased tooth count)
• Renal agenesis(Absent kidney)
• Seizure
• Sensorineural hearing impairment
• Skeletal dysplasia
• Tremor
• Visual impairment(Impaired vision)

Human chorionic gonadotropin injection

Diagnosis

IGD is typically diagnosed in adolescents presenting with absent or partial puberty using biochemical testing that reveals low serum testosterone or estradiol (hypogonadism) that results from complete or partial absence of GnRH-mediated release of LH and FSH (hypogonadotropic hypogonadism [HH]) in the setting of otherwise normal anterior pituitary anatomy and function and in the absence of secondary causes of HH.

Treatment

To induce and maintain secondary sex characteristics, gradually increasing doses of testosterone or human chorionic gonadotropin (hCG) injections in males or estrogen and progestin in females; to stimulate spermatogenesis or folliculogenesis, either combined gonadotropin therapy (hCG and human menopausal gonadotropins [hMG] or recombinant FSH) or pulsatile GnRH therapy. If conception fails despite spermatogenesis in a male or ovulation induction in a female, in vitro fertilization may be an option.

NIH genetic and rare disease info

• NIH info on Kallmann syndrome 1

Kallmann syndrome 1 is a rare disease.

Kallmann syndrome 1 Resources
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