Spinocerebellar ataxia-34 is an autosomal dominant disorder characterized by slowly progressive cerebellar ataxia. The age at onset is usually during the young adult years, and most patients remain ambulatory until late in life. One family with SCA34 also had onset of erythema and hyperkeratosis in early childhood (Cadieux-Dion et al., 2014), whereas other families have additional neurologic signs, including ocular movement disturbances and pyramidal tract signs (Ozaki et al., 2015). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).

Trichorhinophalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Craniofacial features include sparse, slowly growing scalp hair, laterally sparse eyebrows, a bulbous tip of the nose, protruding ears, long flat philtrum, and thin upper vermillion border. The most typical radiographic findings in TRPS are cone-shaped epiphyses, predominantly at the middle phalanges. Hip malformations such as coxa plana, coxa magna, or coxa vara are present in over 70% of patients. In older patients, the hip abnormalities resemble degenerative arthrosis. TRPS3 differs from TRPS1 by the presence of severe brachydactyly, due to short metacarpals, and severe short stature (summary by Ludecke et al., 2001).

Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features including widely spaced eyes and ptosis. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck, and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with NSML do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth restriction resulting in short stature occurs in fewer than 50% of affected persons, although most affected individuals have a height that is less than the 25th centile for age. Sensorineural hearing deficits, present in approximately 20% of affected individuals, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML.

Palmoplantar keratoderma and congenital alopecia-1 (PPKCA1) is a rare autosomal dominant disorder characterized by severe hyperkeratosis and congenital alopecia. Nail changes occur in some patients (summary by Castori et al., 2010). Also see PPKCA2 (212360), an autosomal recessive disorder characterized by congenital alopecia and progressive hyperkeratosis resulting in sclerodactyly, severe contractures and tapering of the digits, and pseudoainhum formation.

Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome is an autosomal dominant disorder characterized by these 4 features, which begin in early childhood and are progressive (summary by Moalem et al., 2015).

A restrictive dermopathy that has material basis in homozygous or compound heterozygous mutation in the ZMPSTE24 gene on chromosome 1p34.