Microphthalmia, Syndromic 1
Patient Information
Characteristics
Background and History
The eye may be abnormally small (microphthalmia) both as an isolated anomaly or as part of a more extensive syndrome as in this disorder. Often other ocular malformations are present as well.
Clinical Correlations
The small eyes are accompanied by small corneas (windshield of the eye) and defects in formation known as colobomas. One or both eyes may be involved. Various skeletal abnormalities such as short stature, ‘caved-in chest” (pectus excavatum), small skull (microcephaly), absence of the clavicle bones, spinal deformities, a highly arched palate, and duplicated thumbs and misshaped digits are usually present. The digits may be curved and sometimes have webbing between them. In addition there are anomalies of the genitalia (males) such as a small penis, an abnormal urethral opening, and small testicles. Some teeth may be missing and the incisors are often malformed and have wide spaces between them. The kidneys can be abnormal as well. More than half (63%) have a degree of intellectual deficit. The ears can be abnormally shaped and may be low-set and rotated posteriorly.
Genetics
Inheritance
This is an X-linked recessive disorder secondary to an unidentified mutation on the X chromosome. Males (with a single X chromosome) are affected but their malformations usually prevent reproduction. No abnormalities are seen in carrier females whose second normal X chromosome apparently covers for the mutation on the other X chromosome.
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.
Diagnosis and Prognosis
The diagnosis is usually made by pediatricians in collaboration with medical geneticists and ophthalmologists. No treatment is available for this syndrome beyond symptomatic and supportive therapy for specific health issues. Blindness is not uncommon.
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