Last updated:
2/26/2025
Years published: 1996, 1997, 2000, 2004, 2009, 2012, 2022, 2025
NORD gratefully acknowledges Anne Slavotinek, PhD, MBBS, Director, Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, for assistance in the preparation of this report.
Lenz microphthalmia syndrome is an extremely rare, inherited eye disorder characterized by small eyes (microphthalmos or microphthalmia) and resulting in visual impairment. Lenz microphthalmia syndrome is typically observed in male infants. Affected infants may have smaller eyes (microphthalmia) or have complete absence of the eyes (anophthalmos or anophthalmia). Additional physical anomalies are often associated, including a small head (microcephaly), differences in the formation of the brain and heart and/or anomalies of the ears and/or fingers and/or toes (digits). Bony abnormalities and anomalies of the kidneys and genitalia may also be present. The range and severity of findings may vary from person to person. Most affected males also have developmental delays and intellectual disability.
Lenz microphthalmia syndrome is typically observed in male infants with a pathogenic or likely pathogenic variant, or gene change, in the BCOR gene. It is inherited in an X-linked pattern. This condition is fully expressed in males only and was initially described in males with a specific gene variant in BCOR, p.Pro85Leu. However, it is now recognized that the condition can be associated with other gene variants in BCOR. Females who carry a pathogenic or likely pathogenic variant in BCOR may have symptoms of a related condition called oculo-facio-cardio-dental (OFCD) syndrome. OFCD has a characteristic facial appearance, eye findings with cataracts and/or microphthalmia and dental and cardiac anomalies. OFCD is more common than Lenz syndrome and has been associated with many different variants in the BCOR gene.
In affected males, the primary physical characteristic associated with Lenz microphthalmia syndrome is small eyes (one eye or both), although the condition has been reported without this ocular anomaly. In most people, both eyes are affected and the eyes maybe of different size (bilateral, asymmetrical microphthalmos/microphthalmia). The front (anterior), clear portion of the eye through which light passes (cornea) may be small (microcornea). In addition, the colored portion of the eye (iris) may be differently formed with absent tissue (coloboma), giving the iris a “keyhole” appearance. Colobomas may also affect other parts of the eye, including the ciliary body, choroid and/or optic disc. In some people, the upper eyelids may droop (blepharoptosis) due to paralysis of muscles that control the eyelids. Rarely, affected infants may have absent or only rudimentary (vestigial) portions of the eyes (anophthalmos or anophthalmia). Such eye findings may result in varying degrees of visual impairment or blindness in some people. Other eye anomalies include increased ocular pressure (glaucoma). The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.
Affected males may have mild to severe delays in attaining certain developmental milestones (e.g., crawling, sitting independently, walking, etc.) and intellectual disability ranging from mild to severe.
Most infants with Lenz microphthalmia syndrome also have additional physical findings, such as head and facial (craniofacial) differences. These can include a small head (microcephaly), abnormalities affecting brain formation and anomalies of the ears and teeth. In most infants with this disorder, the ears are flexed forward (anteverted) and the ear lobes may be large but in some children, the ears may also be small and underdeveloped (hypoplastic). Hearing impairment may be present in some people. The teeth may be widely spaced or abnormally crowded. In addition, the front teeth (incisors) may be absent (dental agenesis or anodontia) or differently formed. Some affected males may have incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove or incomplete closure of the upper lip (cleft lip).
Most males with the disorder also have skeletal anomalies. These may include a lateral (sideways) and front-to-back (anterior-posterior) curvature of the spine (kyphoscoliosis), narrow and/or sloping shoulders, underdeveloped collarbones (hypoplastic clavicles) and/or a differently shaped rib cage (thoracic cage). In some males, fusion of the forearm bones may also be present.
In addition, infants with Lenz microphthalmia syndrome often have anomalies of the fingers and/or toes (digits). The digits may be bent (clinodactyly), flexed (camptodactyly) and/or joined (syndactyly). Approximately half of affected males may also have abnormalities of the reproductive and urinary (genitourinary) systems. These malformations may include failure of the testes to descend into the scrotum (cryptorchidism), placement of the urinary opening (meatus) on the underside of the penis (hypospadias) and/or underdevelopment (hypoplasia) or absence (agenesis) of a kidney (renal agenesis). Heart abnormalities have also been described.
It is possible for females who carry a single variant in the gene for Lenz microphthalmia syndrome (heterozygous carriers) to have some of the symptoms associated with OFCD as above. However, one large study showed that, in at least some females who were related to males with Lenz microphthalmia, changes in the activity of the X chromosome prevented any symptoms.
Lenz microphthalmia syndrome is caused by changes or pathogenic variants in the BCOR gene and is inherited in an X-linked pattern.
X-linked genetic disorders are conditions caused by a disease-causing gene variant on the X chromosome and mostly affect males. Females who have a disease-causing gene variant on one of their X chromosomes are carriers for that disorder. Carrier females usually do not have symptoms because females have two X chromosomes and only one carries the gene variant. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease-causing gene variant, he will develop the disease.
Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
If a male with an X-linked disorder can reproduce, he will pass the gene variant to all his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male children.
Carrier females for the BCOR gene variant first associated with Lenz microphthalmia (p.Pro85Leu) usually do not usually have symptoms. However, some females that have a different BCOR variant may have some of the symptoms associated with OFCD as mentioned above.
At least 15 affected males with fully expressed Lenz microphthalmia syndrome have been reported in the medical literature.
The diagnosis of Lenz microphthalmia syndrome may be confirmed at birth based upon a thorough clinical evaluation, characteristic physical findings and imaging techniques, and genetic testing. Ultrasonography studies of the internal structure of the eye may show that the length from the front to the back of the eye (anteroposterior axis) is smaller than normal, confirming a diagnosis of microphthalmia. In some people, however, it may be difficult to distinguish severe microphthalmia from anophthalmia. Therefore, ultrasound imaging or magnetic resonance imaging (MRI) may sometimes be used to help confirm which condition is present. When MRI scanning is unable to clarify which malformation is present, other diagnostic steps may sometimes be taken to determine whether rudimentary (vestigial) portions of the eyes are present or absent.
Additional diagnostic steps may also be taken to confirm the presence of other physical findings typically associated with Lenz microphthalmia syndrome. Examination with an instrument that visualizes the interior of the eye (ophthalmoscopy or fundoscopy) may be used to determine the absence of ocular tissue in the eye (colobomas). Drooping of the upper eyelid (blepharoptosis) may be diagnosed by clinical examination, including comparison with the other eyelid (if the anomaly affects only one side) or examination of the infant’s upper gaze. Imaging techniques may confirm the presence of dental, skeletal, cardiac, genitourinary and/or other anomalies associated with Lenz microphthalmia syndrome. In some familial cases, Lenz microphthalmia syndrome may be diagnosed before birth (prenatally). For example, ultrasound studies during pregnancy may reveal characteristic findings suggestive of Lenz microphthalmia syndrome in siblings of affected children.
Treatment
The treatment of Lenz microphthalmia syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat diseases of the eye (ophthalmologists); dental specialists who diagnose, prevent, and/or correct anomalies of the teeth (orthodontists); specialists who diagnose and treat skeletal anomalies (orthopedists) and/or others may need to work together to ensure a comprehensive approach to treatment.
Specific therapies for the treatment of Lenz microphthalmia syndrome are symptomatic and supportive. In some people, corrective glasses, contact lenses and/or surgery may be used to help improve vision. Artificial teeth (dentures), dental implants, braces, dental surgery and/or other corrective procedures may be used to correct dental anomalies. Differences in curvature of the spine (kyphoscoliosis) may be treated with a combination of exercises and physical therapy, other supportive techniques, braces, casts and/or corrective surgery. Surgery may also be performed to correct cleft lip and palate; digital, skeletal and/or genitourinary malformations or other anomalies associated with the disorder.
Early intervention is important to ensure that children with Lenz microphthalmia syndrome reach their potential. Special services that may be beneficial for affected children include special education and other medical, social and/or vocational services.
Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be potentially associated with Lenz microphthalmia syndrome.
Genetic counseling is recommended for affected individuals and their families.
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For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
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TEXTBOOK
Opitz JM. Lenz Microphthalmia Syndrome. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:654.
JOURNAL ARTICLES
Ragge N, Isidor B, Bitoun P, et al. Expanding the phenotype of the X-linked BCOR microphthalmia syndromes. Hum Genet. 2019;138(8-9):1051-1069. doi:10.1007/s00439-018-1896-x
Kraus C, et al. Microphthalmia is not a mandatory finding in X-linked recessive syndromic microphthalmia caused by the recurrent BCOR variant p.Pro85Leu. Am J Med Genet A. 2018 ;176:2872-2876.
Ng D, et al. Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR. Nat Genet. 2004;36:411-6.
Ng D, et al. Genetic heterogeneity of syndromic X-linked recessive microphthalmia-anophthalmia: is Lenz microphthalmia a single disorder? Am J Med Genet. 2002;110:308-14.
Forrester S, et al. Manifestations in four males with and an obligate carrier of the Lenz microphthalmia syndrome. Am J Med Genet. 2001;98:92-100.
Traboulsi EI. The Lenz microphthalmia syndrome. Am J Ophthalmol. 1988;105:40-5.
Glanz A, et al. Lenz microphthalmia: a malformation syndrome with variable expression of multiple congenital anomalies. Can J Ophthalmol. 1983;18:41-4.
Baraitser M, et al. Lenz microphthalmia–a case report. Clin Genet. 1982;22:99-101.
Ogunye OO, et al. Linkage studies in Lenz microphthalmia. Hum Hered. 1975;25:493-500.
INTERNET
Ng D. Lenz Microphthalmia Syndrome – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; June 4, 2002. https://pubmed.ncbi.nlm.nih.gov/20301694/ Accessed Feb 6, 2025.
Online Mendelian Inheritance in Man (OMIM). Johns Hopkins University. Microphthalmia, Syndromic 1; MCOPS1. Entry No: 309800. Last Edited 11/09/22. Available at: https://omim.org/entry/309800 Accessed Feb 6, 2025.
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