OMIM ID:
Microphthalmia, Syndromic 1
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Microphthalmia is often a part of other ocular and systemic anomalies. The full range of essential features of Lenz microphthalmia remains unknown but is often diagnosed in males when colobomas and microcornea are associated with mental deficits together with urogenital and skeletal anomalies. Microphthalmos may be unilateral and ocular cysts are common. The globes may be sufficiently small that anophthalmia is sometimes diagnosed but this is a misnomer as some ocular tissue is always present. Sixty per cent of eyes have colobomas which are often bilateral and may involve the optic disc, choroid, ciliary body, and iris. Blindness is common.
Systemic Features
A large number of associated systemic anomalies have been reported with this type of microphthalmia. Skeletal features include microcephaly, spinal deformities, high arched palate, pectus excavatum, absent or dysplastic clavicles (accounting for the narrow or sagging shoulders), and digital anomalies including syndactyly, duplicated thumbs and clinodactyly. Physical growth retardation is evident by shortness of stature. Urogenital malformations are present in 77% of individuals and include hypospadius, cryptorchidism, hydroureter, and renal dysgenesis. Dental anomalies include oligodontia and irregular lower incisors that may be widely spaced. Some degree of intellectual disability is present in 63%. The ears may be abnormally shaped, low-set, rotated posteriorly, and anteverted.
Genetics
Inheritance
This is a rare X-linked disorder that is apparently due to an unknown mutation at Xq27-Xq28. No male-to-male transmission has been observed but affected males rarely reproduce as a result of various urogenital anomalies.
A somewhat similar X-linked syndrome of microphthalmia, sometimes called OFCD syndrome (syndromic 2 microphthalmia; 300166) has been reported to be caused by mutations in BCOR (Xp11.4). This MCOPS2 disorder is often considered to be X-linked dominant with lethality in males.
Another X-linked non-syndromic form of microphthalmia with colobomas has been reported (Microphthalmia with Coloboma, X-Linked; 300345). In addition there is a similar disorder of simple Microphthalmia with Coloboma that is inherited either in an autosomal dominant or autosomal recessive pattern (605738, 610092, 611638, 613703, 251505 ).
Pedigree
X-linked recessive, carrier mother
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.
X-linked recessive, father affected
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.
X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.