What's new AAPOS 2008 - The Private Eye Clinic

Three genes have been identified in patients with JSRD: NPHP1, AHI1, and CEP290.
Homozygous deletion of the NDHP1 gene is causative in 1-2% if JSRD patients with a
distinctive form of the MTS, retinal dystrophy in some, and juvenile nephronophthisis.
Mutations in the AHI1 gene are causative in 10-15%, many of whom exhibit retinal
dystrophy, and in some polymicrogria or later onset nephronophthisis. Mutations in the
CEP290 gene, causing 10% of JSRD are associated with retinal dystrophy and/or
congenital blindness, as well as renal disease in some. Two other JS loci have been
published (9q34 and pericentromeric 11), but the causative genes not yet identified.
They recommend that patients with JSRD be monitored with regular eye exams for
retinal dystrophy and periodic evaluations for renal disease and hepatic fibrosis.
Genotype/phenotype correlation in 325 individuals referred for a diagnosis of
tuberous sclerosis complex in the United States.
Au KS, Williams AT, Roach ES, Batchelor L et al.
Genet Med 2007; 9(2):88-100
The authors performed mutational analysis for the TSC1 and TSC2 genes on 368
randomly ascertained index cases and compared this with the major and minor
diagnostic features and neurobehavioral features to describe the genotype/phenotype
association. Mutations were identified in 72% of the de novo cases, and 77% of the
familial cases. No mutation was identified in 29% and 4% were unclassified. The
individuals with TSC2 mutations had more severe symptoms. Despite the highly
variable expressivity of TSC phenotypes, this study indicated that male patients have
more severe neurologic phenotypes than females. By utilizing meta-analysis of this
data, coupled with data from the other 2 largest studies they were able to demonstrate
that the major diagnostic features, including facial angiofibromas, foehead plaques,
subependymal nodules, renal angiomyolipomas and cysts, retinal phakomas, and
mental retardation are significantly associated with mutations in the TSC2 gene.
Additionally male patients showed more frequent neurologic and eye symptoms, renal
cysts, and ungual fibromas.
Congenital malformations of the eye and orbit.
Guercio JR, Martyn LJ.
Otolaryngol Clin North Am 2007 Feb; 40(1):113-40.
This is an excellent review article discussing not only the embryology, but also specific
congenital malformations and the developmental genes. The authors describe the four
proposed categories of congenital anomalies: 1) single morphogenetic defects, (2)
intrauterine mechanical constraint on an otherwise normal embryo or fetus, (3)
destruction of a normal structure, and (4) dysplasia, defined as a defect in the
differentiation and organization of a tissue. Many of the dysplasias are caused by a
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