MedGen

INSR-related severe syndromic insulin resistance comprises a phenotypic spectrum that is a continuum from the severe phenotype Donohue syndrome (DS) (also known as leprechaunism) to the milder phenotype Rabson-Mendenhall syndrome (RMS). DS at the severe end of the spectrum is characterized by severe insulin resistance (hyperinsulinemia with associated fasting hypoglycemia and postprandial hyperglycemia), severe prenatal growth restriction and postnatal growth failure, hypotonia and developmental delay, characteristic facies, and organomegaly involving heart, kidneys, liver, spleen, and ovaries. Death usually occurs before age one year. RMS at the milder end of the spectrum is characterized by severe insulin resistance that, although not as severe as that of DS, is nonetheless accompanied by fluctuations in blood glucose levels, diabetic ketoacidosis, and – in the second decade – microvascular complications. Findings can range from severe growth delay and intellectual disability to normal growth and development. Facial features can be milder than those of DS. Complications of longstanding hyperglycemia are the most common cause of death. While death usually occurs in the second decade, some affected individuals live longer. [from GeneReviews]

Many types of nonsyndromic congenital nail disorders (NDNC) have been described. Twenty-nail dystrophy (TND), also known as trachyonychia (from the Greek for 'rough nails'), is an autosomal dominant nail dystrophy characterized by excessive longitudinal striations and numerous superficial pits on the nails, which have a distinctive rough sandpaper-like appearance. Occasionally some nails are spared. The slowly progressive condition is usually apparent at birth and may be self-limiting, with spontaneous resolution in some patients (summary by Sehgal, 2007). TND is referred to here as nonsyndromic congenital nail disorder-1 (NDNC1). Genetic Heterogeneity of Nonsyndromic Congenital Nail Disorders Other nonsyndromic congenital nail disorders include koilonychia (NDNC2; 149300); leukonychia (NDNC3; 151600) caused by mutation in the PLCD1 gene (602142) on chromosome 3p22; anonychia/hyponychia (NDNC4; 206800) caused by mutation in the RSPO4 gene (610673) on chromosome 20p13; partial onycholysis with scleronychia (NDNC5; 164800); anonychia of thumbs with onychodystrophy of other nails (NDNC6; 107000); onychodystrophy mapping to chromosome 17p13 (NDNC7; 605779); toenail dystrophy (NDNC8; 607523) caused by mutation in the COL7A1 gene (120120) on chromosome 3p21; onychodystrophy mapping to chromosome 17q25.1-q25.3 (NDNC9; 614149). [from OMIM]

Thickened nails without deformity. [from HPO]