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Aromatase deficiency

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: Increased aromatase activity; Pseudohermaphroditism, female, due to placental aromatase deficiency
SNOMED CT: Maternal virilization due to placental aromatase deficiency (427627006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
Concept ID:
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Gene (location): CYP19A1 (15q21.2)
Monarch Initiative: MONDO:0013301
OMIM®: 613546
Orphanet: ORPHA91


Aromatase deficiency is a rare autosomal recessive disorder in which individuals cannot synthesize endogenous estrogens. If a fetus lacks aromatase activity, dehydroepiandrosterone sulfate produced by the fetal adrenal glands cannot be converted to estrogen by the placenta, and is converted to testosterone peripherally and results in virilization of both fetus and mother. Virilization manifests as pseudohermaphroditism in female infants, with hirsutism and acne in the mother; the maternal indicators resolve following delivery. Affected females are usually diagnosed at birth because of the pseudohermaphroditism. Cystic ovaries and delayed bone maturation can occur during childhood and adolescence in these girls, who present at puberty with primary amenorrhea, failure of breast development, virilization, and hypergonadotropic hypogonadism. Affected males do not present with obvious defects at birth. Their clinical symptoms include tall stature, delayed skeletal maturation, delayed epiphyseal closure, bone pain, eunuchoid body proportions, and excess adiposity. Estrogen replacement therapy reverses the symptoms in males and females (summary by Jones et al., 2007). [from OMIM]

Additional description

From MedlinePlus Genetics
Aromatase deficiency is a condition characterized by reduced levels of the female sex hormone estrogen and increased levels of the male sex hormone testosterone.

Females with aromatase deficiency have a typical female chromosome pattern (46,XX) but are born with external genitalia that do not appear clearly female or male. These individuals typically have normal internal reproductive organs, but develop ovarian cysts early in childhood, which impair the release of egg cells from the ovaries (ovulation). In adolescence, most affected females do not develop secondary sexual characteristics, such as breast growth and menstrual periods. They tend to develop acne and excessive body hair growth (hirsutism).

Men with this condition have a typical male chromosome pattern (46,XY) and are born with male external genitalia. Some men with this condition have decreased sex drive, abnormal sperm production, or testes that are small or undescended (cryptorchidism).

There are other features associated with aromatase deficiency that can affect both males and females. Affected individuals are abnormally tall because of excessive growth of long bones in the arms and legs. The abnormal bone growth results in slowed mineralization of bones (delayed bone age) and thinning of the bones (osteoporosis), which can lead to bone fractures with little trauma. In affected individuals, the body does not respond correctly to the hormone insulin, so people with aromatase deficiency can have abnormally high blood sugar (glucose), a condition known as hyperglycemia. In addition, people with armoatase deficiency can have excessive weight gain and a fatty liver.

Women who are pregnant with fetuses that have aromatase deficiency often experience mild symptoms of the disorder even though they themselves do not have the disorder. These women may develop hirsutism, acne, an enlarged clitoris (clitoromegaly), and a deep voice. These features can appear as early as 12 weeks of pregnancy and go away soon after delivery.  https://medlineplus.gov/genetics/condition/aromatase-deficiency

Clinical features

From HPO
Ovarian cyst
MedGen UID:
Concept ID:
Disease or Syndrome
The presence of one or more cysts of the ovary.
Primary amenorrhea
MedGen UID:
Concept ID:
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Female pseudohermaphroditism
MedGen UID:
Concept ID:
Congenital Abnormality
Hermaphroditism refers to a discrepancy between the morphology of the gonads and that of the external genitalia. In female pseudohermaphroditism, the genotype is female (XX) and the gonads are ovaries, but the external genitalia are virilized.
Delayed skeletal maturation
MedGen UID:
Concept ID:
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Hypergonadotropic hypogonadism
MedGen UID:
Concept ID:
Disease or Syndrome
Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAromatase deficiency

Professional guidelines


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Clinical prediction guides

Berkane N, Liere P, Lefevre G, Alfaidy N, Nahed RA, Vincent J, Oudinet JP, Pianos A, Cambourg A, Rozenberg P, Galichon P, Rousseau A, Simon T, Schumacher M, Chabbert-Buffet N, Hertig A
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Recent systematic reviews

Yami Channaiah C, Memon SS, Sarathi V, Lila AR, Barnabas R, Raghav D, Bhandare VV, Arya S, Thakkar H, Patil VA, Karlekar M, Kunwar A, Bandgar T
Ann Endocrinol (Paris) 2024 Feb;85(1):48-55. Epub 2023 Jun 20 doi: 10.1016/j.ando.2023.05.010. PMID: 37348676
Fan L, Zhang B, Li L, Gong C
Clin Endocrinol (Oxf) 2020 Dec;93(6):687-695. Epub 2020 Jul 27 doi: 10.1111/cen.14277. PMID: 32623730

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