GENETIC DISEASE	NAME	OMIM	CHROMOSOME LOCALIZATION	GENE	GENETICS	ANIMAL MODEL	FEATURES
BULLOUS ERYTHRODERMA ICHTHYOSIFORMIS CONGENITA, BULLOUS ICHTHYOSIFORM ERYTHRODERMA, EPIDERMOLYTIC HYPERKERATOSIS	EHK	113800	17q21-q22, 12q13	KRT1, KRT10	AD 1:300000		Widespread bullous disease at birth. Erythematous, blister hyperkeratosis.
SKIN PEELING SYNDROME, FAMILIAL CONTINUOUS, KERATOLYSIS EXFOLIATIVA CONGENITA		270300			AR, very rare		Type A: asymptomatic peeling Type B: erythema and pruritus, separation between stratum corneum and granulosum. Sometime short stature
HARLEQUIN FETUS		242500	11q13?, 18q ?		AR, rare	ichq chrm 19	Thick plates of scales ectropion and eclabium, lethal. Male with harlequin ichthyosis with a de novo deletion of the long arm of chromosome 18; the karyotype was 46,XY,del(18)(q21.3)
ICHTHYOSIS BULLOSA OF SIEMENS, ICHTHYOSIS EXFOLIATIVA	IBS	146800	12q11-q13	KRT2E	AD, rare		May present erythema and blistering. In later weeks, large, dark gray hyperkeratoses predominantly on the arms and legs
ICHTHYOSIS HYSTRIX, CURTH-MACKLIN TYPE	IHCM	146590		KRT1 (1 report 2001)	AD, rare		Plaques and spiny hyperkeratosis, erythroderma may be present at birth. defect of tonofibrils, excluded linkage with cluster of keratin genes on 12q and 17q, however one report mutation in a keratin gene (KRT1) (JID 2001)
ICHTHYOSIS HYSTRIX GRAVIOR, LAMBERT TYPE ICHTHYOSIS, PORCUPINE MAN		146600			AD		Similar or same of bullous congenital ichthyosiform erythroderma
ICHTHYOSIS VULGARIS		146700	1q21		AD, 1:250	flaky tail (ft)	Fine, white mild to moderate scaling, usually not present at birth., rare collodion baby. Profilaggrin and filaggrin are reduced or absent
LAMELLAR ICHTHYOSIS, TYPE 1	LI1	242300	14q11.2	TGM1	AR, 1:200000		After presenting at birth with a collodion-like membrane encasing the neonate, the skin later develops large, brown, platelike scales covering the entire body. No erithroderma. Sometimes a condition like ordinary ichthyosis simplex is present for the rest of the patient's life.
LAMELLAR ICHTHYOSIS, TYPE 2	LI2	601277	2q33-35		AR, 1:200000		In a genomewide search with polymorphic microsatellite markers, they found a maximum 2-point lod score of 7.60 at theta = 0 with D2S137. Final interval was covered by a single YAC which was 2.2 Mb long.
LAMELLAR ICHTHYOSIS, TYPE 3	LI3	604777	19p12-q12		AR, 1:200000		Mapping to chromosome 19 in 6 families. Homozygosity was demonstrated by haplotype analysis for a considerable number of microsatellite markers from the pericentric region, 19p12-q12.
LAMELLAR ICHTHYOSIS, DOMINANT FORM		146750			AD		The disorder is congenital with generalized involvement. Affection of the palms and soles is only slight. Pruritis is a striking feature. Collodion membrane at birth.
NONBULLOUS CONGENITAL ICHTHYOSIFORM ERYTHRODERMA 1, ICHTHYOSIFORM ERYTHRODERMA, CONGENITAL, NONBULLOUS	NCIE1CIE	242100	14q11.2; 3p21	TGM1 and others	AR		At birth erithrodermic scaling infant with ectropion and eclabium, colloidon membrane is common. Erithroderma. It is associated with growth retardation, oligophrenia, spastic paralysis, genital hypoplasia, hypotrichia, and shortened life-expectancy. Genetic heterogeneity: Am J Hum Genet 2000 66(3):904
NETHERTON SYNDROME	NETH	256500	5q32	SPINK5	AR		Congenital ichthyosiform erythroderma associated with thin and fragile 'bamboo hair' (trichorrhexis invaginata. Nodules along hair length). Gene encoding the serine protease inhibitor LEKTI.
X-LINKED ICHTHYOSIS, STEROID SULFATASE DEFICIENCY		308100	Xp22.32	ARSC1 (ARYLSULFATASE C)	XR, 1:2000-9500 male		Brown adherent scales. Onset is at birth, and scalp, ears, neck, and one or more flexures are involved, with more striking scaling on the abdomen than on the back, and extension of the scaling down the front of the leg onto the dorsum of the foot.
EPIDERMOLYSIS BULLOSA SIMPLEX, DOWLING-MEARA, EPIDERMOLYSIS BULLOSA HERPETIFORMIS		131760	17q12-q21, 12q13	KRT5, KRT14	AD		Onset during the first 3 months of life and is characterized by generalized bullae in herpetiform arrangement. Serous and hemorrhagic blisters occur most frequently on the palms and soles, around the mouth, and on the trunk and neck. Severe and presence on electron microscopy of large cytoplasmic clumps of tonofilaments, which are intermediate filaments composed of keratin
WEBER-COCKAYNE TYPE EPIDERMOLYSIS BULLOSA SIMPLEX, EPIDERMOLYSIS BULLOSA OF HANDS AND FEET		131800	17q12-q21, 12q13	KRT5, KRT14	AD		Hands and feet
EPIDERMOLYSIS BULLOSA SIMPLEX, KOEBNER TYPE	EBS2	131900	17q12-q21, 12q13	KRT5, KRT14	AD		Generalized distribution of blisters
EPIDERMOLYSIS BULLOSA SIMPLEX, OGNA TYPE, EPIDERMOLYSIS BULLOSA SIMPLEX-1	EBS1	131950	8q24		AD		Hands and feet Occurrence of skin bruising
EPIDERMOLYSIS BULLOSA SIMPLEX WITH MOTTLED PIGMENTATION	EBS-MP	131960	12q13	KRT5	AD		Recurrent blistering from birth resembles that of EBS Koebner, in addition the patients showhyper- and hypopigmented spots giving the skin, especially of the limbs, a mottled 'dirty' appearance. Premature aging of the skin, mild bruisability of the legs, and longitudinally curved nails are features.
JUNCTIONAL (basement membrane)
EPIDERMOLYSIS BULLOSA, JUNCTIONAL, HERLITZ-PEARSON TYPE, EPIDERMOLYSIS BULLOSA LETALIS		226700	1q32, 1q25-q31, 18q11.2	LAMININ 5	AR		Congenital absence of skin in localized areas is probably due to intrauterine trauma and bullae. The hands and feet are relatively spared.
EPIDERMOLYSIS BULLOSA LETALIS WITH PYLORIC ATRESIA		226730	17q11-qter, Chr.2	INTEGRINa6§4	AR		Blisters and patchy lack of skin. Intestinal obstructions, especially pyloric atresia or stenosis
EPIDERMOLYSIS BULLOSA JUNCTIONALIS, DISENTIS TYPE, EPIDERMOLYSIS BULLOSA, GENERALIZED ATROPHIC BENIGN		226650	1q32, 17q11-qter, 10q24.3	COL17A1, INTEGRIN §3	AR		Adult form of junctional epidermolysis bullosa, present at birth, severe blistering not lethal
ERYTHROKERATODERMIA VARIABILIS, GREITHER DISEASE	EKV	133200	1p34-p35	CONNEXIN 31, 30.3	AD		Patches of hyperkeratosis and erythematous areas
ERYTHROKERATODERMIA, PROGRESSIVE SYMMETRIC, DARIER-GOTTRON DISEASE	PSEK	602036	1q21, 1p35.1, 1p35.1	LORICR.CONNEXIN 31	AD		Symmetric and well delineated areas of erythroderma
PITYRIASIS RUBRA PILARIS, KERATOSIS CIRCUMSCRIPTA		173200			AD		Scaly and horny productions situated chiefly in the sebaceous follicles and by a more or less generalized hyperemia
KERATOLYTIC WINTER ERYTHEMA, OUDTSHOORN SKIN	KWE	148370	8p23-p22		AD		Intermittent and recurrent centrifugal peeling with redness, of the palms and soles in particular. In more severe cases, similar patches were found extending up the limbs to the buttocks and to the trunk.
ACROKERATOELASTOIDOSIS	AKE	101850	2p?		AD		The palms and soles are primarily affected, but involvement may extend to the dorsum of the hands and feet in severe cases. The lesions are papules nodular and yellow with hyperkeratotic surfaces.
POROKERATOSIS PUNCTATA PALMARIS ET PLANTARIS	PPPP	175860			AD
ACROKERATOSIS VERRUCIFORMIS, HOPF DISEASE		101900			AD		Warty hyperkeratotic lesions are found on the dorsal aspect of the hands and feet and on the knees and elbows.
DARIER-WHITE DISEASE, KERATOSIS FOLLICULARIS	DAR	124200	12q23-q24.1	ATP2A2	AD		Formation of greasy keratotic papules located especially in the seborrheic areas.
PLAMOPLANTAR KERATODERMIA WITH DEAFNESS, VOHWINKEL SYNDROME		124500	13q11-q12	CONNEXIN 26	AD		Congenital deafness with keratoderma of palm and sole, and finger and toe constrictions
VOHWINKEL SYNDROME WITH ICHTHYOSIS, MUTILATING KERATODERMA WITH ICHTHYOSIS		604117	1q21	LORICRIN	AD
PALMOPLANTAR KERATODERMA, EPIDERMOLYTIC; HYPERKERATOSIS, LOCALIZED EPIDERMOLYTIC, UNNA-THOST DISEASE	EPPK	144200	17q12-q21	KRT9	AD		Diffuse yellow palmoplantar keratoderma on a erythematous base
KERATOSIS PALMARIS ET PLANTARIS WITH ESOPHAGEAL CANCER, TYLOSIS WITH ESOPHAGEAL CANCER	TOC	148500	17q24		AD
KERATODERMIA PALMOPLANTARIS PAPULOSA, BUSCHKE-FISCHER-BRAUER TYPE	PPK	148600	12q-17q?		AD		Keratotic papules on palms, soles, and volar surface of fingers and toes, papules are from few to hundreds
KERATOLYTIC WINTER ERYTHEMA, OUDTSHOORN SKIN	KWE	148370	8p23-p22		AD		Intermittent and recurrent centrifugal peeling with redness, of the palms and soles in particular. In more severe cases, similar patches were found extending up the limbs to the buttocks and to the trunk.
KERATOSIS PALMOPLANTARIS STRIATA I	PPKS1	148700	18q12.1-q12.2	DSG1 (DESMOGLEIN)	AD		The lesions of the hands consist of a streak of hyperkeratosis running the length of each finger and onto the palm. A cluster of genes for desmosomal cadherins, desmogleins , and desmocollins have been mapped to the same region, making them good candidates for this form of PPK.
KERATOSIS PALMOPLANTARIS STRIATA II	PPSK2	125647	6p24	DSP (DESMOPLAKIN)	AR
MAL DE MELEDA		248300	8qter		AR		Congenital symmetrical cornification of the palms and soles, with ichthyotic changes elsewhere, characterizes this disorder which derives its name from its relatively high frequency among inhabitants of the Island of Meleda, Dalmatia, Yugoslavia.
KERATOSIS PALMOPLANTARIS WITH PERIODONTOPATHIA, APILLON-LEFEVRE SYNDROME	PALS	245000	11q14.1-q14.3	CTSC (CATHEPSIN C)			Both the milk teeth and the permanent teeth are lost prematurely. The skin lesions are very similar or identical to those of mal de Meleda
SCLEROTYLOSIS, SCLEROATROPHIC AND KERATOTIC DERMATOSIS OF LIMBS HURIEZ SYNDROME; HRZ	TYS	181600	4q23		AD		The characteristics were atrophic fibrosis of the skin of the limbs, hypoplasia of nails, and keratodermia of the palms and soles.
KERATOSIS, FOCAL PALMOPLANTAR AND GINGIVAL		148730			AD		Focal palmoplantar and marginal gingival hyperkeratosis. The most marked hyperkeratosis is in weight-bearing areas of the soles and pressure-related areas of the palms. Changes appear in early childhood and progress. Male-to-male transmission was observed.
KERATODERMA, PALMOPLANTAR, NORRBOTTEN RECESSIVE TYPE		244850					In a study of the palmoplantar keratoderma in the northernmost county of Sweden (Norrbotten), Gamborg Nielsen (1985) found a seemingly recessive and unusually severe form. This differed from the picture of mal de Meleda (248300).
POROKERATOSIS OF MIBELLI		175800			AD		This is a rare hereditary keratoatrophoderma characterized by centrifugally spreading patches surrounded by narrow horny ridges and with central atrophy. The lesions are craterlike. Many cases in Italy. Skin eruption usually begins by middle age and about 7% of patients eventually develop skin cancer, usually on the extremities.
POROKERATOSIS PLANTARIS, PALMARIS, ET DISSEMINATA		175850			AD		Characteristically, lesions appeared first on the palms and soles (in the late teens or early 20s) and subsequently on other parts of the body including areas not exposed to ultraviolet radiation.
POROKERATOSIS, DISSEMINATED SUPERFICIAL ACTINIC DSAP	DSAP	175900	12q23.2-q24.1		AD		Lesions, which occur almost only in sun-exposed areas of the skin, develop after age 16 years, with penetrance nearly complete by age 30 or 40. DSAP is much more frequent than porokeratosis of Mibelli from which it must be distinguished.
POROKERATOSIS PUNCTATA PALMARIS ET PLANTARIS	PPPP	175860			AD
CALLOSITIES, PAINFUL PLANTAR		114140			AD		Painful callosities over pressure points in the hands and feet
KERATOSIS FOLLICULARIS SPINULOSA DECALVANS CUM OPHIASI	KFSD	308800	Xp22.2-p22.13		XR, AD		Affected men show thickening of the skin of the neck, ears, and extremities, especially the palms and soles, loss of eyebrows, eyelashes and beard, thickening of the eyelids with blepharitis and ectropion, and corneal degeneration.
KYRLE DISEASE		149500			sporadic/AD		Kyrle disease is a follicular keratosis. The horny papules may be situated anywhere except the palms, soles and mucous membranes. They eventually acquire a central keratotic plug that upon removal leaves a crater that matches the shape of the plug (Kyrle sign). The lesions come in crops, last several weeks, and eventually disappear with minimal or no scarring.
FLEGEL DISEASE, HYPERKERATOSIS LENTICULARIS PERSTANS	HLP	144150			AD		Similar to Kirle disease. Hyperkeratotic papules on legs and feet.
ATROPHODERMIA VERMICULATA, FOLLICULITIS ULERYTHEMATOSA		209700			AD		The skin changes are usually limited to the face and consist of symmetrical, small, crowded areas of skin atrophy producing pits with sharp edges and an overall worm-eaten appearance.
HAILEY-HAILEY DISEASE, BENIGN CHRONIC PEMPHIGUS	BCPM	169600	3q21-q24	ATP2C1	AD		Recurrent eruption of vesicles and bullae involving predominantly the neck, groin, and axillary regions is characteristic of this disorder.
RESTRICTIVE DERMOPATHY, TIGHT SKIN CONTRACTURE SYNDROME		275210			AR		Lethal, severe intrauterine growth retardation, congenital contractures, and tense skin that is easily eroded. The skin is drawn tightly over the face causing a narrow, pinched nose, small mouth, limited jaw mobility. No organ malformations are found. Histologically, the skin showed hyperkeratosis.
KERATOSIS PILARIS		604093	chr.18?		AR?		Follicular hyperkeratosis and frequently occurring with ichthyosis or atopy. Ulerythema ophryogenes is keratosis pilaris affecting the follicles of the eyebrow hairs, associated with erythema, and often leading to scarring and atrophy. The short arm of chr 18 is a candidate region.
SEBORRHEIC KERATOSES		182000			AD		A raised, sharply demarcated, brown pigmented, papule or plague which result from proliferation of squamous basaloid cells which sit on top of and do not invade the dermis. The skin lesions of the basal cell nevus syndrome sometimes resemble seborrheic keratoses.
SYNDROMIC DISORDERS
CHILD SYNDROME, CONGENITAL HEMIDYSPLASIA WITH ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS		308050	Xq28	NSDHL (NAD(P)H STEROID DEHYDROGENASE-LIKE PROTEIN	XD	Bare patches (Bpa) and Striated (Str)	Male lethal. Many organs are asymmetric with hypoplasia on the side of ichthyosis and limb malformation.
CHONDRODYSPLASIA PUNCTATA 1	CDPX1	302950	Xp22.3	ARSE (arylsulfatase E)	XR		Clinically mild. Ichthyosis, scarring alopecia,mental retardation, and bone changes (short stature). Franco et al.: A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy.
CHONDRODYSPLASIA PUNCTATA 2, CONRADI-HUNERMANN SYNDROME	CDPX2	302960	Xp11.23-p11.22	EBP (delta(8)-delta(7) sterol isomerase emopamil-binding protein)	XD	Tattered (Td)	Male lethal. In female punctate epiphyseal calcifications and ichthyotic skin lesions are both transient, resolving during early infancy. Non-skin defects include abnormal cranofacies, muscoskeletal and ocular abnormalities.
CHONDRODYSPLASIA PUNCTATA, AUTOSOMAL DOMINANT, CONRADI-HUNERMANN SYNDROME		118650			AD		Epiphyseal, frequently asymmetric calcifications and dysplastic skeletal changes. Skin changes occur in about 28% of cases of both forms. Cataracts are consistently absent in the autosomal dominant form and present in about two-thirds of the rhizomelic and X-linked dominant (302950) forms.
RHIZOMELIC CHONDRODYSPLASIA PUNCTATA, TYPE 1	RCDP1	215100	6q22-q24	PEX7 peroxisomal type 2 targeting signal (PTS2) receptor	AR		Rare, multisystem, developmental disorder, presence of foci of calcification in hyaline cartilage, coronal vertebral clefting, dwarfing, joint contractures, congenital cataract, ichthyosis, and severe mental retardation.
RHIZOMELIC CHONDRODYSPLASIA PUNCTATA, TYPE 2	RCDP2	222765	chr1	GNPAT (glyce ronephosphate o-acyltransferase)	AR?
ICHTHYOSIS AND MALE HYPOGONADISM, RUD SYNDROME		308200			XR?		Neurocutaneous disorder characterized by epilepsy, mental retardation, infantilism, congenital ichthyosis, and retinitis pigmentosa.
ZUNICH NEUROECTODERMAL SYNDROME, CHIME (oculo Colobomas, congenital Heart disease, early onset Ichthyosiform dermatosis, Mental retardation and Ear anomalies, Epilepsy) SYNDROME		280000			AR?		Early-onset migratory ichthyosiform dermatosis, bilateral ocular coloboma, conductive hearing loss, seizures, mental retardation, and remarkably similar facial features.
KID SYNDROME, ICHTHYOSIFORM ERYTHRODERMA, CORNEAL INVOLVEMENT, AND DEAFNESS		242150			AD/AR		Congenital erythroderma, then focal hyperkeratotic plaques, associated with hypotrichosis and nail dystrophy. Association of deafness and corneal involvement (Tadini G.)
NEU-LAXOVA SYNDROME	NLS	256520			AR		The Neu-Laxova syndrome is a lethal dysplasia-malformation syndrome with abnormalities of placentation, severe intrauterine growth retardation, edema, ectodermal dysplasia, and the CAD complex with severe CNS developmental defect.
ICHTHYOTIC NEUTRAL LIPID STORAGE DISEASE, CHANARIN-DORFMAN DISEASE, ICHTHYOSIFORM ERYTHRODERMA WITH LEUKOCYTE VACUOLATION		275630	3p21	CGI58 (homology with members of a large family defined by an alphabeta hydrolase fold)	AR		Rare form of nonbullous congenital ichthyosiform erythroderma, hepatosplenomegaly, vacuolated granulocytes (Jordans anomaly), and myopathy
REFSUM DISEASE, HEREDOPATHIA ATACTICA POLYNEURITIFORMIS		266500	10pter-p11.2	PHYH, phytanoyl-CoA hydroxylase	AR		Similar to ichthyosis vulgaris, may be limited to palmoplantar keratoderma. Retinitis pigmentosa, chronic polyneuropathy, and cerebellar signs. Most cases have electrocardiographic changes, and some have nerve deafness.
RICHNER-HANHART SYNDROME, TYROSINE TRANSAMINASE DEFICIENCY		276600	16q22.1-q22.3	TAT	AR		Ichthyosis and retinitis pigmentosa. Oculocutaneous syndrome characterized by herpetiform corneal ulcers and painful punctate keratoses of digits, palms, and soles
ICHTHYOSIS FOLLICULARIS, ATRICHIA, AND PHOTOPHOBIA SYNDROME	IFAP	308205			XR?		Follicular ichthyosis, alopecia, and photophobia
ICHTHYOSIS, MENTAL RETARDATION, DWARFISM, AND RENAL IMPAIRMENT		242530			AR		In an Iranian family, Passwell et al. (1975) described a combination of congenital ichthyosis, mental retardation, dwarfism, and renal impairment. Two sisters and a brother were affected as well as a female who was a half sister of both parents.
ICHTHYOSIS, HEPATOSPLENOMEGALY, AND CEREBELLAR DEGENERATION		242520			AR/XR?		3 brothers had ichthyosis and a progressive neurologic disorder. Dysarthria and ataxia began after age 50. The ichthyosis was of distinctive type. Normal steroid sulfatase excluded the X-linked form . The hepatosplenomegaly suggested a storage disease, but its nature was not evident.
ICHTHYOSIS WITH ALOPECIA, ECLABION, ECTROPION, AND MENTAL RETARDATION		242510			AR		In an inbred North-Swedish family, ichthyosis-mental retardation syndrome distinct from the Sjogren-Larsson syndrome (SLS), which is unusually frequent in the same area.
ICHTHYOSIS, SPLIT HAIRS, AND AMINOACIDURIA		242550			AR		Single family Similar to Netherton disease, but the ichthyosis is lamellar and the hair abnormality is 'split hairs.' Collodion babies, one mentally retarded. Excess of arginine, serine, lysine and alanine and absence of proline and hydroxyproline in urine.
ICHTHYOSIS--CHEEK--EYEBROW SYNDROME, ICE SYNDROME		146720			AD		One family in which persons in 4 generations showed a combination of ichthyosis vulgaris, prominent and full cheeks, sparse lateral eyebrows, and certain other craniofacial and musculoskeletal defects such as high-arched palate, kyphoscoliosis, anterior chest deformity, and pes planus.
SJOGREN-LARSSON SYNDROME, ICHTHYOSIS, SPASTIC NEUROLOGIC DISORDER, AND OLIGOPHRENIA	SLS	270200	17p11.2	FALDH fatty alcohol dehydrogenase	AR		The skin changes in Sjogren-Larsson syndrome are similar to those of congenital ichthyosiform erythroderma. Associated abnormalities include neurologic disorder as spastic quadriplegia, mental retardation and retinopathy
NAXOS DISEASE, WOOLLY HAIR, PALMOPLANTAR KERATODERMA, AND CARDIAC ABNORMALITIES		601214	17q21	PLAKOGLOBIN	AR		Palmoplantar keratoderma and other ectodermal features with cardiac disorders suggesting arrhythmogenic right ventricular dysplasiacardiomyopathy
CARDIOMYOPATHY, DILATED, WITH WOOLLY HAIR AND KERATODERMA		605676	6p24	DSP DESMOPLAKIN	AR	KO mice embryonic lethal (skin-specific in newborn)	Epidermolytic palmoplantar keratoderma, woolly hair, and dilated cardiomyopathy. Same gene causing keratosis palmoplantaris striata II (AD), but in this case the mutation is in homozygosity.
SCHOPF-SCHULZ-PASSARGE SYNDROME KERATOSIS PALMOPLANTARIS WITH CYSTIC EYELIDS, HYPODONTIA, AND HYPOTRICHOSIS ECCRINE TUMORS WITH ECTODERMAL DYSPLASIA		224750			AD/AR?
KERATODERMA, PALMOPLANTAR, WITH DEAFNESS		148350	13q11-q12	connexin 26			Nonepidermolytic palmoplantar keratoderma and sensorineural deafness.
KERATODERMA, PALMOPLANTAR, WITH NAIL DYSTROPHY AND HEREDITARY MOTOR-SENSORY NEUROPATHY, CHARCOT-MARIE-TOOTH DISEASE WITH PALMOPLANTAR KERATODERMA AND NAIL DYSTROPHY		148360			AD		Syndrome of palmoplantar keratoderma, dystrophy of the fingernails, and hereditary motor and sensory neuropathy in 10 members of 4 generations. Genetic heterogeneity.
EPIDERMOLYSIS BULLOSA SIMPLEX AND LIMB-GIRDLE MUSCULAR DYSTROPHY		226670	8q24	PLECTIN	AR		Muscular dystrophy associated with epidermolysis bullosa simplex.
EPIDERMOLYSIS BULLOSA, MACULAR TYPE	EBM	302000	Xq27.3-qter				The features are formation of bullae without evident trauma, absence of all hair, hyperpigmentation, depigmentation, acrocyanosis, dwarfism, microcephaly, mental inferiority, short tapering fingers, and sometimes anomalies of the nails. The disorder is lethal to affected males early in life.
EPIDERMOLYSIS BULLOSA DYSTROPHICA NEUROTROPHICA, EPIDERMOLYSIS BULLOSA WITH CONGENITAL DEAFNESS EPIDERMOLYSIS BULLOSA PROGRESSIVA, RECESSIVE	EBR3	226500	4q28-q31?				Localized traumatic blistering in late childhood or adolescence, onset of nail manifestations several years before the skin manifestations, diffuse and slowly progressive skin atrophy of hands, feet, elbows, knees, palms and soles, with loss of dermal ridge pattern of fingers, occasional blistering of oral mucosa and congenital, slowly progressive perceptive deafness.
EPIDERMOLYSIS BULLOSA, LATE-ONSET LOCALIZED JUNCTIONAL, WITH MENTAL RETARDATION		226440			AR?
DYSKERATOSIS CONGENITA, X-LINKED, ZINSSER-COLE-ENGMAN SYNDROME	DKC	305000	Xq28	DKC1 (DYSKERIN)	XR		Characterized by reticulate skin pigmentation, nail dystrophy, and mucosal leukoplakia. Progressive bone marrow failure. An increased risk of developing different types of malignancies also exists. Dyskerin is a nuclear protein involved in ribosomal RNA processing
DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT, DYSKERATOSIS CONGENITA, SCOGGINS TYPE		127550	3q21-q28	TERC (TELOMERASE RNA CANDIDATE 3)	AD		Dyskeratosis congenita is a progressive bone marrow failure syndrome that is characterized by abnormal skin pigmentation, leukoplakia, and nail dystrophy
DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE		224230			AR		It is not yet known whether the autosomal recessive and autosomal dominant forms represent separate disease loci.
KERATOSIS PALMOPLANTARIS WITH PERIODONTOPATHIA AND ONYCHOGRYPOSIS, COCHIN JEWISH DISORDER, HAIM-MUNK SYNDROME	HMS	245010	11q14.1-q14.3	CATHEPSIN C			Rare syndrome of congenital palmoplantar keratosis, pes planus, onychogryphosis, periodontosis, arachnodactyly, and acroosteolysis.
MENTAL RETARDATION WITH SPASTIC PARAPLEGIA AND PALMOPLANTAR HYPERKERATOSIS, FITZSIMMONS SYNDROME		309560			XR		Single family: 4 brothers affected, 3 sisters normal.
CORNEODERMATOOSSEOUS SYNDROME, CORNEAL DYSTROPHY, EPITHELIAL, WITH SKIN AND SKELETAL CHANGES	CDO	122440			AD		Unique corneal changes with diffuse palmoplantar hyperkeratosis, distal onycholysis, brachydactyly, short stature, premature birth and dental problems. One family
HAIR FOLLICLE DISEASE
ALOPECIA UNIVERSALIS CONGENITA, ATRICHIA, GENERALIZED, ATRICHIA WITH PAPULAR LESIONS		203655/209500	8p21.2	HR, HAIRLESS	AR/AD		Scalp, eyelashes, eyebrows, and body hair were affected but not completely absent. This rare disorder is clearly distinct from alopecia areata (104000), which has an autoimmune basis with probable genetic predisposition.
ALOPECIA AREATA		104000					Alopecia areata is a chronic inflammatory disease characterized by patchy hair loss with T-cell infiltration of hair follicles. It occurs in approximately 0.1% of the general population, but in approximately 9% of patients with Down syndrome.
LOOSE ANAGEN HAIR SYNDROME		600628			AD		Anagen hairs are easily pulled from the scalp. The disorder presents in childhood with hair that is relatively sparse and does not grow long. Hair of fair color, hair shafts of reduced caliber, and an early age of onset are features.
ANDROGENETIC ALOPECIA, MALE-PATTERNED BALDNESS		109200			AD in males?		Autosomal dominant in males and to be autosomal recessive in females who transmit the trait if heterozygous but are bald only if homozygous
FOCAL FAMILIAL ALOPECIA		104110					One family. 14-year-old girl and her mother who had patchy hair loss present from early childhood. When studied in transverse section, biopsy specimens from both women showed marked anagen-telogen transformation that appeared to be irreversible. Preservation of telogen epithelium with absence of inflammation and scarring distinguished familial focal alopecia from pseudopelade (alopecia cicatrisata) and from localized alopecia areata.
HYPOTRICHOSIS SIMPLEX	HTS	605389	18p11.32-p11.23		AD		Hair is present in hereditary hypotrichosis simplex but is diffusely thinned.
HYPOTRICHOSIS, MARIE UNNA TYPE, MARIE UNNA HEREDITARY HYPOTRICHOSIS	MUHH	146550	8p21				Distinghished from hypotrichosis simplex by the presence of a twisting hair dystrophy. Genetic interval about 12 cM. By mutation analysis, exluded the hairless gene as well as 9 other genes expressed in skin that are located with the linkage region as candidates for the disorder.
HYPOTRICHOSIS SIMPLEX OF SCALP, HYPOTRICHOSIS, SPANISH TYPE	HTSS	146520	6p21.3		AD		Progressive, gradual loss of scalp hair beginning in the first decade and leading to almost complete loss of scalp hair. A few sparse, fine, short hairs remain in some individuals. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. Men and women are equally affected.
HYPERTRICHOSIS UNIVERSALIS, HYPERTRICHOSIS LANUGINOSA CONGENITA		145700			AD		generalized persistent growth of dark lanugo hair.
HYPERTRICHOSIS, CONGENITAL GENERALIZED	HCG	307150	Xq24-q27.1		XD		Males were more severely affected than females. Affected females showed asymmetric, somewhat patchy hirsutism consistent with lyonization. It lies within a 22-cM interval between DXS425 and DXS1227
DISTICHIASIS, TWO ROWS OF EYELASHES		126300			AD
TRISTICHIASIS, THREE ROWS OF EYELASHES		190800			AD
HYPERTRICHOSIS TERMINALIS, GENERALIZED, WITH GINGIVAL HYPERPLASIA, FIBROMATOSIS, GINGIVAL, WITH HYPERTRICHOSIS		135400			AD		There is no necessary relationship between the age of development of the gingival changes and the hypertrichosis. The latter may be present at birth but often appears at puberty.
HYPERTRICHOSIS CUBITI, HAIRY ELBOWS		139600			?		Short stature has been described to associate with this syndrome
HYPERTRICHOSIS, ANTERIOR CERVICAL		600457			?
MONILETHRIX		158000	12q13	HB1, HB6	AD		Expression of monilethrix is variable; in mild cases, dystrophic hair may be confined to the occiput but more severely affected individuals have near total alopecia. In some cases alopecia persists throughout life; in others, regrowth of apparently normal hair may occur in adolescence or, temporarily, in pregnancy. Hairs are not twisted. They are evenly spaced with wide (normal) and narrow (abnormal) regularly distruted nodes.
PSEUDOMONILETHRIX		177750			?		In monilethrix the hairs show regularly spaced fusiform, spindle-shaped or elliptical swellings. The nodes are the normal diameter of the shaft and the intermodes represent atrophic parts. In pseudomonilethrix the nodes are irregularly spaced and the internodes represent the normal hair-shaft caliber.
PILI ANNULATI, RINGED HAIR		180600			AD		Alternating light and dark bands are visible on the hair. The light areas are due to inclusion of air in the cortex. The hair tends to break off at these points.
PILI TORTI, TWISTED HAIR		261900			AD or AR		The shafts of the hairs are flattened at irregular intervals and twisted through 180 degrees about their axes. The hair, which is coarse, dry, and lusterless, breaks off, leaving a stubble of variable length.
UNCOMBABLE HAIR SYNDROME, PILI TRIANGULI ET CANALICULI		191480			AD		Scanning electron microscopy shows two specific alterations of the hair: a triangular cross-section and a longitudinal groove
WOOLLY HAIR, AUTOSOMAL DOMINANT		194300			AD		The hair is short, tightly curled, and woolly, resembling that of a black.
WOOLLY HAIR, AUTOSOMAL RECESSIVE		278150			AR		The hair is blond and the diameter of the hair shaft is reduced. All the cases have, it seems, been sporadic, and the recessive hypothesis rests merely on the fact that the parents of 1 patient were second cousins.
HAIRY PALMS AND SOLES		139650			AD		Single family. Patches of thickened hair-bearing skin on the palms of both hands.
HAIRY ELBOWS		139600					Associated with short stature
HYPOTRICHOSIS WITH LIGHT-COLORED HAIR AND FACIAL MILIA		146530			AD?
SYNDROMIC HAIR ABNORMALITIES
LEPRECHAUNISM		246200	19p13.2	INSULIN RECEPTOR	AR		Severe intrauterine growth retardation; small, elfin-like face with protuberant ears; distended abdomen; relatively large hands, feet, and genitalia; and abnormal skin with hypertrichosis, acanthosis nigricans, and decreased subcutaneous fat.
HYPERTRICHOSIS, CONGENITAL ANTERIOR CERVICAL, WITH PERIPHERAL SENSORY AND MOTOR NEUROPATHY		239840			AR
POLYCYSTIC OVARY SYNDROME 1, HYPERANDROGENEMIA	PCO	184700	15q23-q24, 5q11.2		AD		Obesity, hirsutism, and amenorrhea are clinical correlates of enlarged polycystic ovaries. Prevalence of hirsutism varied from 2 to 8% depending on the chosen cut-off. fundamental defect In many cases of PCO disease is increased 5-alpha-reductase activity in the liver and skin. As a result, testosterone is converted to the more potent androgen dihydrotestosterone, leading to hirsutism.
HYPOTRICHOSIS, CONGENITAL, WITH JUVENILE MACULAR DYSTROPHY	HJMD	601553	16q22.1	P-CADHERIN	AR?
MENKES SYNDROME, KINKY HAIR DISEASE, COPPER TRANSPORT DISEASE	MNK	309400	Xq12-q13	Copper ATPase-transporter	XR		Associated with neurologic and vascular abnormalities. Hair is fine, wiry, silver or white and fragile.
PILI TORTI AND NERVE DEAFNESS, BJORNSTAD SYNDROME	BJS	262000	2q34-q36		AR		Sparse curly scalp hair, pili torti, sensorineural deafness
UNCOMBABLE HAIR, RETINAL PIGMENTARY DYSTROPHY, DENTAL ANOMALIES, AND BRACHYDACTYLY, BORK SYNDROME		191482			AD		Ectodermal dysplasia with congenital hypotrichosis and uncombable hair, associated with juvenile cataracts, retinal pigmentary dystrophy, oligodontia, and brachymetacarpy.
WOOLLY HAIR, HYPOTRICHOSIS, EVERTED LOWER LIP, AND OUTSTANDING EARS, SALAMON SYNDROME		278200			AR		A single family
TRICHORHINOPHALANGEAL SYNDROME, TYPE I	TRPS1	190350	8q24.12	TRPS1, transcription factor	AD		Haploinsufficiency of a specific zinc finger protein that is a putative transcription factor
LANGER-GIEDION SYNDROME, TRICHORHINOPHALANGEAL SYNDROME, TYPE II	TRPS2	150230	8q24.11-q24.13	TRPS1, EXT1	?		Similarities to the trichorhinophalangeal syndrome type I, particularly with regard to facies, bulbous nose, sparse hair, and cone-shaped epiphyses. Distinguishing features are mental retardation, microcephaly, multiple exostoses, and redundant skin. Less consistent features include hyperextensible joints, recurrent upper respiratory tract infections, and delayed speech development. All cases have been sporadic and a majority have been males. contiguous gene syndrome involving loss of functional copies of the TRPS1 and EXT1 genes.
TRICHORHINOPHALANGEAL SYNDROME, TYPE III, SUGIO-KAJII SYNDROME	TRPS3	190351	8q24.12	TRPS1, transcription factor	?		Presence of severe brachdactyly, generalized shortening of all phalanges and metacarpals differentiate the condition from TRPS1 and the absence of mental deficiency and exostoses from TRPS2
TRICHODENTOOSSEOUS SYNDROME	TDO	190320	17q21.3-q22	DLX3, transcription factor	AD		Enamel hypoplasia and hypocalcification with associated strikingly curly hair. 2 possibly distinct types had been reported. TDO-I (Lichtenstein et al., 1972) is characterized by kinky or curly hair, dolichocephaly, enamel hypoplasia, increased dental caries, radial dense bones, and occasionally brittle nails. The chondrocranium shows some thickening but calvarial density and thickness are normal. Premature fusion of cranial sutures, especially the sagittal, is responsible for dolichocephaly. Persons with TDO-II (Leisti and Sjoblom, 1978) show sparse as well as curly hair, more striking nail changes, and thickening and sclerosis of the calvaria. Males show narrowing of the ear canal. Dental eruption is delayed in TDO-I and precocious in TDO-II. In TDO-II, dentin is dysplastic whereas it is normal in TDO-I.
ALOPECIA-MENTAL RETARDATION SYNDROME WITH CONVULSIONS AND HYPERGONADOTROPIC HYPOGONADISM		601217
ALOPECIA-EPILEPSY-OLIGOPHRENIA SYNDROME OF MOYNAHAN		203600
ALOPECIA-MENTAL RETARDATION SYNDROME		203650
GIANT AXONAL NEUROPATHY 1	GAN1	256850	16q24.1	GIGAXONIN (cytoskeletral, ubiquitous)	AR		Chronic polyneuropathy of childhood accompanied by characteristically kinky hair and unique posture of legs. Sensorineural neuropathy affecting both the peripheral nerves and the central nervous system, is characterized by neurofilament accumulation, leading to segmental distention of axons.
DIARRHEA, FATAL INFANTILE, WITH ABNORMAL HAIR, TRICHORRHEXIS BLASTYSIS		222470					Single family. Severe diarrhea, lethal. Woolly, easily removed black hair, at the scanning microscopy with projections at multiple sites arising from the convex surface of a kinked hair and suggesting buds. The hair had a low content of cystine and an abnormal content of several other amino acids.
TRICHORRHEXIS NODOSA SYNDROME, POLLITT SYNDROME TRICHOTHIODYSTROPHY-NEUROCUTANEOUS SYNDROME		275550			?		Mental and physical retardation and trichorrhexis nodosa. Microcephaly and abnormal cerebral cortical cell layering were associated with reduction in the content of high sulfur protein in hair.
HAIR-BRAIN SYNDROME, AMISH BRITTLE HAIR SYNDROME BIDS SYNDROME, TRICHOTHIODYSTROPHY, INCLUDED TTD, INCLUDED		234050			AR		Short stature, intellectual impairment, brittle hair, and decreased fertility. Microscopically, hairs showed an irregular, grooved surface lacking in scales. Trichothiodystrophy (TTD): conditions of brittle hair with markedly reduced sulfur content.
TRICHOTHIODYSTROPHY, ICHTHYOSIFORM ERYTHRODERMA WITH HAIR ABNORMALITY AND MENTAL AND GROWTH RETARDATION; TAY SYNDROME; IBIDS SYNDROME	TTD	601675	19q13.2-q13.3	ERCC2XPB, ERCC3XPB	AR		Trichothiodystrophy: sulfur-deficient brittle hair. Patients with trichothiodystrophy have brittle hair and nails (because of reduced content of cysteine-rich matrix proteins), ichthyotic skin, and physical and mental retardation. Approximately half of the patients display photosensitivity, correlated with a nucleotide excision repair (NER) defect.
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A	XPA	278700	9q22.3	XPAC			Sensitivity to sunlight with the development of carcinoma at an early age is a leading feature of xeroderma pigmentosum. Onset, with freckle-like lesions in exposed areas, usually occurs in the first years of life.
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP B	XPB	133510	2q21	ERCC3
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP D; TRICHOTHIODYSTROPHY WITH SUN SENSITIVITY	XPD	278730	19q13.2-q13.3	ERCC2	AR		Similar to 601675, with photosensititvity
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C	XPC	278720	3p25	XPC
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP E	XPE	278740	11p12-p11	DDB1 (DNA damage-binding protein)			Mild, rare
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F	XPF	278760	16p13.3-p13.13	ERCC4			Mild, very rare (only in Japan)
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP G	XPG	278780	13q33	ERCC5			Very rare and clinically heterogenous
WOOLLY HAIR, HYPOTRICHOSIS, EVERTED LOWER LIP, AND OUTSTANDING EARS, SALAMON SYNDROME		278200			AR		A single report
BRITTLE HAIR AND MENTAL DEFICIT, SABINAS BRITTLE HAIR SYNDROME		211390			AR		Dry, brittle, fragile hair and mental deficit in a village in Mexico
ALOPECIA-CONTRACTURES-DWARFISM MENTAL RETARDATION SYNDROME, ACD MENTAL RETARDATION SYNDROME		203550			AR
HAIR DEFECT WITH PHOTOSENSITIVITY AND MENTAL RETARDATION		234030			AR?		Single family
CERVICAL HYPERTRICHOSIS WITH UNDERLYING KYPHOSCOLIOSIS		117850					Congenital localized hypertrichosis occurs most often over the spine, usually in the sacral area, producing a 'faun tail.' Similar localized hypertrichosis has been reported in the lumbar thoracic and cervical regions; however, cutaneous markers of underlying skeletal or neural abnormalities.
HYPERTRICHOTIC OSTEOCHONDRODYSPLASIA		239850			AR?		Cutaneous hypertrichosis and skeletal changes
AMAUROSIS CONGENITA, CONE-ROD TYPE, WITH CONGENITAL HYPERTRICHOSIS		204110			AR?		Single family. Retinal dystrophy characterized by visual impairment from birth and profound photophobia in the absence of night blindness. Associated in both girls was trichomegaly, bushy eyebrows with synophrys, and excessive facial and body hair
CATARACT, HYPERTRICHOSIS, MENTAL RETARDATION SYNDROME, CAHMR SYNDROME		211770					Single family.
ABLEPHARON-MACROSTOMIA SYNDROME	AMS	200110			AR?		Absent eyelids, eyebrows, and eyelashes; fusion defects of the mouth; rudimentary external ears; ambiguous genitalia; absent or rudimentary nipples; coarse, dry skin with redundant skin folds.
ALOPECIA, PSYCHOMOTOR EPILEPSY, PYORRHEA, AND MENTAL SUBNORMALITY		104130			AD		Single family. The alopecia was congenital, permanent, and universal.
SPONDYLOEPIMETAPHYSEAL DYSPLASIA WITH HYPOTRICHOSIS, WHYTE SYNDROME		183849			AD
TRICHODYSPLASIA-XERODERMA		190360					Single family. The disorder combined various degrees of trichodysplasia and xeroderma. Trichodysplasia was a general term they used for all types of hair disturbances from alopecia and hypotrichosis to structural changes such as pili torti and trichorrhexis nodosa.
THUMB DEFORMITY AND ALOPECIA		188150			AD
HYPOGONADISM, PRIMARY, AND PARTIAL ALOPECIA		241090			AR?		Single family
HYPOGONADISM, DIABETES MELLITUS, ALOPECIA, MENTAL RETARDATION, AND ELECTROCARDIOGRAPHIC ABNORMALITIES, WOODHOUSE-SAKATI SYNDROME		241080			AR?
HYPOTHYROIDISM, ATHYROIDAL, WITH SPIKY HAIR AND CLEFT PALATE, BAMFORTH-LAZARUS SYNDROME		241850	9q22	TTF2/FoxE1	AR		Single family. Thyroidal hypothyroidism, spiky hair, choanal atresia, cleft palate, and bifid epiglottis. Polyhydramnios was present in the third trimester in both pregnancies.
NAIL DISORDERS
LEUKONYCHIA TOTALIS		151600			AD		White color of the nails
NAIL DYSPLASIA, TWENTY-NAIL DYSTROPHY, ONYCHODYSTROPHY TOTALIS, ISOLATED		161050			AD		Flattening, thinning, pitting and longitudinal striatons of the nail plate. The change in the nails is usually evident at birth and progresses slowly with complete loss by the age of 10-20. . Occurring in children entirely free of other skin, hair and teeth abnormalities
NAIL DYSPLASIA, ISOLATED CONGENITAL		605779	17p13				Nail alterations were mostly present since birth and soon reached an individually variable degree of severity. Affected persons showed longitudinal streaks and thinning of nail plates, mostly of all fingernails and toenails, with some accentuation of the thumbnail and big toenails, poorly developed lunulae, longitudinal angular ridges of individual nail plates occasionally starting proximally from a reddish prominence, platonychia and koilonychia of individual nails often overgrowing the lateral folds, and notches and fissures of the free margins. Findings were generally more severe in children less than 12 years old, and males tended to be more severely affected than females.
ANONYCHIA-ONYCHODYSTROPHY		107000			AD or AR		Some digits show absent nails while others show dystrophic nails. In some reported families absence of some or all nails apparently occurred without associated manifestations of the nail-patella syndrome and without absence of digits as in the anonychia-ectrodactyly syndrome.
ANONYCHIA		206800					Congenital complete anonychia
KOILONYCHIA, HEREDITARY		149300			AD		Spoon nails
SYNDROMIC NAIL DISORDERS
ANONYCHIA-ONYCHODYSTROPHY WITH HYPOPLASIA OR ABSENCE OF DISTAL PHALANGES, COOKS SYNDROME		106995					Characterized by onychodystrophy, anonychia, brachydactyly of the fifth finger, and digitalization of the thumbs, with absence or hypoplasia of the distal phalanges of the hands and feet.
NAIL-PATELLA SYNDROME, ONYCHOOSTEODYSPLASIA TURNER-KIESER SYNDROME FONG DISEASE	NPS	161200	9q34.1	LMX1B LIM HOMEO BOX TRANSCRIPTION FACTOR 1	AD		Dysplasia of the nails and absent or hypoplastic patellae are the cardinal features but others are iliac horns, abnormality of the elbows interfering with pronation and supination, and in some cases nephropathy.
PACHYONYCHIA CONGENITA, TYPE 1, JADASSOHN-LEWANDOWSKY SYNDROME	PC1	167200	17q12-q21, 12q13	KRT16, KRT6	AD		Characterized by onychogryposis, hyperkeratosis of the palms, soles, knees and elbows, tiny cutaneous horns in many areas, and leukoplakia of the oral mucous membranes. Hyperhidrosis of the hands and feet is usually present.
PACHYONYCHIA CONGENITA, RECESSIVE		260130			AR		Single family
PACHYONYCHIA CONGENITA, TYPE 2, JACKSON-LAWLER TYPE	PC2	167210	17q12-q21, 12q13	KRT17, KRT6B