Leprechaunism
Victor A. McKusick, OMIM, Johns Hopkins University, April 18, 2007
[for Professionals mainly]
Donohue Syndrome; Insulin Receptor, Defect
Gene Map Locus: 19p13.2
Donohue and Uchida (1954) observed 2 sisters with ... cessation of growth at about the seventh month of gestation, peculiar facies creating a gnome-like appearance ... severe endocrine disturbance indicated by emaciation, enlargement of breasts and clitoris, and histologic changes in the ovaries, pancreas and breasts ... The patients died at 46 and 66 days of age, respectively ... Schilling et al. (1979) found a defect in insulin receptors in a Canadian Indian infant ... Profound hyperinsulinemia and insulin receptor function in cultured fibroblasts ... hypertrophy of pancreatic beta cells was noted ... Bier et al. (1980) concluded that hypoglycemia in leprechaunism is due to an accelerated fasting state. Elfin facial appearance, growth retardation, severely diminished subcutaneous adipose tissue stores, decreased muscle mass, hypertrichosis, pachyderma, and acanthosis nigricans were cited as notable clinical features ... Reddy and Kahn (1989) demonstrated a functional abnormality of the epidermal growth factor receptor (131550), as well as of the insulin receptor, in 3 unrelated patients with leprechaunism ... The type A syndrome of insulin resistance and acanthosis nigricans showed no abnormality of EGF receptor ... Clinical Synopsis ... Prenatal growth, Failure to thrive, Emaciation, Delayed osseous maturation ... Insulin resistance ... Elfin facies, Protuberant ears, Low-set ears, Poorly developed ears, Flat nasal bridge, Flared nostrils, Thick lips, Macrostomia, Microcephaly, Hypertelorism, High arched palate ... Neonatal breast enlargement ... Large clitoris, Large genitalia, Cystic ovarian enlargement ... Absent subcutaneous fat, Hirsutism, Pachyderma, Acanthosis nigricans ... Decreased muscle mass ... Distended abdomen, Umbilical hernia, Inguinal hernia ... Relatively large hands

Insulin Receptor
Victor A. McKusick, OMIM, Johns Hopkins University, May 15, 2007
Insulin Receptor, Defect ... and Acanthosis Nigricians, Included, Diabetes Mellitus, Insulin-Resistant, With Acanthosis Nigricians, Included
Gene Map Locus: 19p13.2
The insulin (INS; 176730) receptor is a tetramer of 2 alpha and 2 beta subunits ... Taylor et al. (1986) concluded that a patient with leprechaunism and extreme insulin resistance was a genetic compound, i.e., that each parent had transmitted to the proband a different defect of the insulin receptor ... Kahn et al. (1976) divided the syndrome of insulin resistance and acanthosis nigricans into two: type A, a syndrome of younger females with signs of virilization and accelerated growth in whom a defect in cell receptors for insulin may be primary; and type B, a syndrome in older females with signs of an immunologic disease in whom circulating antibodies to the insulin receptor are found ... Allelic Variants ... Leprechaunism (246200) is an autosomal recessive disorder due to a defect in the INSR gene ... found 2 different mutant alleles of the INSR gene. The patient was a compound heterozygote ... Mutation in either the structural gene or some of the processing steps may lead to insulin (INS; 176730) resistance of various forms, either in the homozygous, heterozygous, or compound heterozygous state. These include: (a minority of cases of) mild insulin-resistant diabetes mellitus with acanthosis nigricans, minor physical abnormalities and sometimes polycystic ovaries (Moller et al., 1994; see 147670.0030), or the Rabson-Mendenhall syndrome (Kadowaki et al., 1990; see 147670.0012); leprechaunism (Hone et al., 1994; e.g., 147670.0033); and a predisposition to noninsulin-dependent diabetes mellitus ('t Hart et al., 1996; e.g., 147670.0029) ... Clinical Synopsis ... Insulin-resistant diabetes mellitus, Leprechaunism (homozygous or compound heterozygous), Rabson-mendenhall syndrome (homozygous) ... Acanthosis nigricans ... Ketoacidosis rare ... Virilization in younger females, Polycystic ovaries, Clitoromegaly, Menstrual irregularity, Medullary sponge kidneys ... Bitemporal skull narrowing... Lipodystrophy, Acral hypertrophy (enlarged ears, nose, chin and finger tips) ... Brachydactyly ... Exophthalmos ... Supernumerary teeth, Severe, premature caries, Prominent lower canines and upper incisors ... Generalized hypertrichosis ... Insulin receptor defect, Defective insulin-binding, Hyperprolactinemia ...

Patterson Pseudoleprechaunism
Victor A. McKusick, OMIM, Johns Hopkins University, January 14, 1995
Patterson and Watkins (1962) described a 10-month-old boy who they thought had leprechaunism. Discordant features, however, were normal birth weight (rather than the usual severe intrauterine growth retardation) and marked cutis gyrata of hands and feet as well as a generalized skeletal disorder. (Patterson, 1969) ... The boy also had hyperadrenocorticism and diabetes mellitus. He developed bladder diverticula and died at age 7.5 years from gram-negative sepsis ...

Leprechaunism: Picture of the Month
Archives Pediatrics & Adolescent Medicine, Vol. 152 No.10, October 1998
THIS 5-MONTH-OLD infant, the product of a consanguineous marriage, now weighs 3500 g. He has a lifelong history of poor growth with high blood glucose levels unresponsive to insulin. Recurrent rectal prolapse has resulted in chronic mechanical intestinal obstruction ... left, The infant shows the typical "elfinlike" facies of leprechaunism with hirsutism, large, low-set ears, broad nasal tip and flared nares, and thick lips ... Clinical Features: Donohue and Donohue and Uchida were the first to describe this rare syndrome featuring dysmorphic facies, failure to thrive, hirsutism, and multiple endocrine abnormalities. Leprechaunism was the euphemistic name used to describe the "elfinlike" facies and poor growth characteristic of the syndrome. The dysmorphic facial features include large, low-set ears, depressed nasal bridge with a broad nasal tip and flared nares, thick lips, and hirsutism. The body habitus is striking with a marked lack of subcutaneous fat, generalized hirsutism, acanthosis nigricans, prominent nipples, enlarged genitalia, abdominal distention, and loose skin ...

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Last Updated: 2008/1/16

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