OMIM ID:
Hypotrichosis with Juvenile Macular Degeneration
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Macular dystrophy usually becomes symptomatic before the second decade of life but retinal evidence of macular degeneration can be seen in the first decade. EOG is usually normal while the ERG responses are decreased early and with time decrease further in amplitude. Pattern reversal VEPs are significantly subnormal even while vision is relatively good. Visual acuity decreases slowly in spite of significant deterioration of cone- and rod-mediated retinal function. Retinal pigmentary changes consisting of irregular clumping and areas of hypopigmentation are evident in the macular and perimacular areas and sometimes beyond. Most patients eventually become blind.
Systemic Features
Scalp hair loss occurs during the first months of life but the alopecia does not affect eyebrows or eyelashes unlike that seen in the EEM disorder (225280) which in addition has digital and dental anomalies. Partial regrowth may occur during puberty. Light and electron microscopy of hair shafts may reveal pili torti, longitudinal ridging with scaling, and fusiform beading but these are not present in all patients.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from homozygous mutations in the CDH3 gene located at 16q22.1.
EEM syndrome (225280) is an allelic disorder with similar hair and retinal features plus dental, digital and limb anomalies. The hypotrichosis also involves the eyebrows and eyelashes in this disorder, however.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.