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Disease Profile

Leydig cell hypoplasia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q56.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

46,XY disorder of sex development due to LH resistance or LHB deficiency; 46,XY disorder of sex development due to luteinizing hormone resistance or luteinizing hormone beta subunit deficiency; 46,XY DSD due to LH resistance or LHB deficiency;

Summary

Leydig cell hypoplasia (LCH) is a disorder that impairs male sexual development. It causes incomplete development of Leydig cells, which are cells in the testicles (testes) that secrete male sex hormones (androgens). These hormones are needed for normal male sexual development as reproductive organs are forming (before birth), as well as during puberty. A genetic male with LCH has typical male chromosomes (46, XY), but due to low androgen levels, may have a range of genital differences.[1][2][3]

In a genetic male with LCH, the external genitalia may not look clearly male or female (ambiguous genitalia). Specific features of LCH may include a small penis (micropenis), a urethra opening (hole) on the underside of the penis rather than at the tip (hypospadias), and a scrotum that is divided into two halves (bifid scrotum). A person with a severe form of LCH may have only female external genitalia, and small undescended testes (located in the pelvis, abdomen, or groin).[1][3] Males with severe LCH may not develop secondary sex characteristics during puberty, such as increased body hair, facial hair, and a deeper voice.[2]

LCH is caused by mutations in the LHCGR gene and inheritance is autosomal recessive.[1][2] There is no standard treatment for LCH. Treatment depends on the features and severity in each person and may include hormone therapy; surgery for undescended testes, removal of testes, or to correct genital differences; and assisted reproductive technology for infertility.[3][4] A team of specialists often work together to identify treatment options for a person with LCH.

Of note: Genetic females (46, XX) can also inherit the mutations that cause LCH in males. Genetic females with these mutations have normal female external genitalia and normal female development during puberty, but may have amenorrhea (absent periods) and infertility.[5]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Absence of secondary sex characteristics
0008187
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Aplasia of the uterus
Absent uterus
uterus absent

[ more ]

0000151
Breast aplasia
Absent breast
0100783
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Decreased serum testosterone level
Decreased serum testosterone levels
Low serum testosterone level
Low serum testosterone levels

[ more ]

0040171
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Female hypogonadism
0000134
Hyoplasia of the Leydig cells
0010790
Hypergonadotropic hypogonadism
0000815
Hypospadias
0000047
Increased circulating gonadotropin level
Elevated gonadotropins
Elevated serum gonadotropins
Gonadotropin excess

[ more ]

0000837
Male hypogonadism
Decreased function of male gonad
0000026
Male pseudohermaphroditism
0000037
Micropenis
Short penis
Small penis

[ more ]

0000054
Primary amenorrhea
0000786
Primary gonadal insufficiency
0008193
5%-29% of people have these symptoms
Abnormal vas deferens morphology
0012872
Secondary amenorrhea
Previous menstrual periods stop
0000869
Testicular gonadoblastoma
0000030
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        General Information

          In-Depth Information

          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

            References

            1. Leydig cell hypoplasia. Genetics Home Reference. April 2010; https://ghr.nlm.nih.gov/condition/leydig-cell-hypoplasia.
            2. O'Neill MJF. LEYDIG CELL HYPOPLASIA, TYPE I. Online Mendelian Inheritance in Man (OMIM). March 31, 2015; 3/31/2015.
            3. Bakircioglu ME, Tulay P, Findikli N, Erzik B, Gultomruk M, Bahceci M. Successful testicular sperm recovery and IVF treatment in a man with Leydig cell hypoplasia. J Assist Reprod Genet. Jul 31, 2014; 31(7):817-821. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096883/.
            4. Xu Y, Chen Y, Li N, et al. Novel compound heterozygous variants in the LHCGR gene identified in a subject with Leydig cell hypoplasia type 1. J Pediatr Endocrinol Metab. January 26, 2018; 31(2):239-245. https://www.ncbi.nlm.nih.gov/pubmed/29305568.
            5. Sperling MA. Chapter 5 Ambiguous genitalia : Summary of Disorders Associated with Ambiguous Genitalia. In: Witchel SF, Lee PA. Pediatric Endocrinology (Fourth Edition). Philadelphia, PA: Elsevier, Inc; 2014; 107-156.