boards’ fodder

Bones, Eyes, and Nails

With contributions from Elise M. Herro, MD, Benjamin A. Solky, MD, and Jennifer L. Jones, MD. (Updated July 2015*)

CONDITION INHERITANCE: GENE BONE EYES NAILS

5-FU,AZT, antimalarials Blue lunulae

Acne Fulminans Osteolytic Lesions (sterno-

clavicular)

AEC (Ankyloblepharon AD: p63 Anodontia/hypodontia Ankyloblepharon (strands of Onychodysplasia or anonychia

filiforme adenatum- skin), lacrimal duct abnormalities
Ectodermal dysplasia-Cleft
palate) [Hay-Wells Syndrome]

Albright’s Osteodystrophy Bradymetacarpalism

Alkaptonuria AR: homogentisate Severe arthropathy (larger Pingueculae, Osler’s Sign (blue-
1,2-dioxygenase (HGO) joints) gray scleral pigment)

Allezandrini Syndrome Unilateral retinitis pigmentosa,

eyelash poliosis

Alopecia Areata Nail Pits, Red and Spotted Lunula

Apert’s Syndrome FGFR2 Craniosynostosis, syndactyly One large fingernail

Argyria Blue Sclera Slate Blue Lunula

Arsenic poisoning, rheumatic Mee’s Lines (all nails)

fever, CHF

Ataxia-Telangiectasia (Louis- AR: ataxia-telangiectasia Bulbar Telangiectasia

Bar Syndrome) mutated (ATM)

Bacterial Infection Black nail (Proteus mirabilis);

Green nail (Pseudomonas)

Beare-Stevenson Cutis Gyrata FGFR2 Craniosynostosis

Syndrome

Behçet’s Syndrome A/w HLA-B51 Asymmetric, non-erosive Retinal vasculitis, posterior

polyarthritis uveitis, & hypopyon

Bonnet Dechaune Blanc Unknown Retinal AVM’s

Syndrome (Wyburn-Mason)

Bushke-Ollendorf Syndrome AD: LEMD3 or MAN1 Osteopoikolosis

Chanarin-Dorfman Syndrome ABHD5 Short stature Cataracts, nystagmus, ectropion

(Neutral lipid storage disease
with ichthyosis)

Chédiak-Higashi Syndrome AR: LYST Photophobia, nystagmus,

strabismus

CHF, Connective Tissue Red Lunula

Disease, CO Poisoning,
Alopecia Areata

CHIME Syndrome AR: PIGL Colobomas of Retina

(Coloboma, Heart defects,
Ichthyosiform Dermatosis,
Mental retardation, Ear
abnormalities)

Cicatricial Pemphigoid Ab against β-4-integrin Symblepharon, scarring,

blindness

Cirrhosis, CHF, diabetes Terry’s Nails

Cockayne’s Syndrome (CS) AR: Dwarfism; intracranial Salt & Pepper Retinitis
CSA: ERCC8 gene calcifications Pigmentosa with Optic Atrophy;
CSB: ERCC6 gene Cataracts

Coffin-Siris Syndrome Microcephaly 5th nail dystrophy/anonychia

Congenital Contractural AD: fibrillin 2 Arachnodactyly, scoliosis,

Arachnodactyly crumpled ears

Congenital Ichthyosiform AR: transglutaminase Ectropion

Erythroderma (CIE) 1 (TGM1), ALOX12B/
[Nonbullous CIE] ALOXE3 (lipoxygenase)

Congenital Onychodysplasia Anonychia

of the Index finger (COIF)

Congenital Syphilis Early: 0-2 yrs Early: Wimberger’s sign Late: interstitial keratitis
(sawtooth metaphysis)

Late: >2 yrs Late: osteochondritis, Clutton’s

joints (knees), Higoumenaki’
sign (medial clavicle), saddle
nose, saber shins, mulberry
molars, Hutchinson’s teeth

D­Rirections
in
esidency p. 1 • Winter 2002
 boards’ fodder
Bones, Eyes, and Nails
With contributions from Elise M. Herro, MD, Benjamin A. Solky, MD, and Jennifer L. Jones, MD. (Updated July 2015*)

CONDITION INHERITANCE: GENE BONE EYES NAILS

Conradi-Hünermann Syndrome XLD: Emopamil-binding Unilateral limb shortening, Asymmetric Focal Cataracts
(Chondrodysplasia punctata) protein (EBP) Chondrodysplasia punctata
XLR: Arylsulfatase E (stippled epiphyses); scoliosis
AR: PEX 7, DHAPAT,
alkyldihydroacetone
phosphate synthase

Cornelia de Lange Syndrome Sporadic (most); Microcephaly, clinodactyly of

AD: nipped-β-like (NIPBL) 5th finger
and SMC1L1

Darier-White Disease AD: ATP2A2 (encoes Red and white longitudinal bands,
(Keratosis follicularis) SERCA2) V-nicking

Deafness, Congenital Anonychia

Onychodystrophy, Recessive
form (DOOR)

Dermatomyositis Samitz sign (cuticle fraying)

Down’s Syndrome Trisomy 21 Clinodactyly Brushfield spots (periphery

of iris)

Dyskeratosis Congenita XLR (most common): Dental caries with early tooth Dystrophic with longitudinal ridges,
(Zinsser-Engman-Cole dyskerin (DKC1) loss; intracranial calcification pterygium; atrophic
Syndrome) AD: telomerase RNA
component (TERC)

EEC Syndrome (Ectrodactyly- AD: EEC1; EEC2; Ectrodactyly (“lobster-claw Lacrimal gland/duct Onychodystrophy
Ectodermal Dysplasia-Cleft EEC3 (p63 gene - most deformity”); Hypodontia/ abnormalities
lip/palate Syndrome) common) anodontia

Ehlers-Danlos VI AR: procollagen lysyl Severe kyphoscoliosis Keratoconus, ruptured globe,

(Kyphoscoliosis) 2-oxoglutarate 5 retinal detachment, blindness,
dioxygenase (PLOD) blue sclera

Ehlers-Danlos VIIA,B AD: COL1A1 (type A) or Congenital hip dislocation,

(Arthrochalasia) COL1A2 (type B) scoliosis, short stature

Ehlers-Danlos IX XLR: lysyl oxidase Occipital horns

Epidermal Nevus Syndrome Sporadic Kyphoscoliosis, Coloboma, corneal opacity,

(Icthyosis hystrix) hemihypertrophy cortical blindness

Fabry Disease (Angiokeratoma XLR: α-galactosidase Whorl-like corneal opacities,

corporis diffusum) A (GLA) spoke-like cataracts

Fanconi’s Anemia AR: FANC Absent radius or thumb, Strabismus, retinal hemorrhages
microcephaly, growth
retardation

Fe++ Deficiency Koilonychia

Franceschetti-Jadassohn Malaligned great toes

Syndrome

Fungal Infection Distal subungal (T. rubrum);

Proximal white subungal (T. rubrum
- often a/w HIV)
Superficial (T. mentag)

Gardner’s Syndrome AD: adenomatous Craniofacial osteomatosis; Congenital Hypertrophy of

polyposis coli (APC) supernumerary teeth Retinal Pigmented Epithelium
(CHRPE)

Gaucher’s Disease AR: acid-β-glucocidase Pingueculae

(GBA)

Goltz’s Syndrome (Focal XLD: PORCN Osteopathia Striata, Lobster Coloboma, microphthalmia
Dermal Hypoplasia) Claw Deformity

Gorlin’s Syndrome (Basal Cell AD: PTCH1 Bifid Rib, Mandibular Hypertelorism, coloboma
Nevus Syndrome) Keratocysts, Kyphoscoliosis,
Calcified Falx Cerebri, Frontal
Bossing

Haim-Munk Syndrome AR: cathepsin C gene Loss of teeth d/t severe Onychogryphosis
periodontitis; arachnodactyly,
acro-osteolysis

Hallerman-Streiff Syndrome Bird-like facies, natal teeth Microopthalmia, Congenital

Cataracts, Strabismus

Harlequin Fetus AR: ABCA12 Ectropion

Hemochromatosis AR: HFE Koilonychia

Hermansky-Pudlak Syndrome AR: HPS1 (most common) Photophobia, nystagmus,

and HPS2/AP3B1 decreased visual acuity

www.aad.org/DIR Winter 2002 • p. 2 D­Rirections

in
esidency
 boards’ fodder
Bones, Eyes, and Nails
With contributions from Elise M. Herro, MD, Benjamin A. Solky, MD, and Jennifer L. Jones, MD. (Updated July 2015*)

CONDITION INHERITANCE: GENE BONE EYES NAILS

Hidrotic Ectodermal Dysplasia AD: connexin 30 (GJB6) Tufting of terminal phalanges, Onychodystrophy, micronychia or
(Clouston syndrome) thickened calvarium anonychia, hyperconvex, brittle,
paronychia

High Fever, Surgery, & Meds Beau’s Lines

(chemo)

Homocystinuria AR: cystathionine Marfanoid habitus, pectus Downward lens displacement,

β-synthase (CBS) excavatum, genu valgum glaucoma

Hyper-IgE Syndrome (Job AD: STAT3 Retained primary teeth and

Syndrome) AR: DOK8 lack of secondary teeth; broad
TYK2 nasal bridge

Hyperthyroidism Koilonychia

Hypoalbuminemia, nephrotic Muehrcke’s nails (lines disappear

syndrome, liver disease when squeezed)

Hypohidrotic Ectodermal XLR: ectodysplasin (EDA) Frontal bossing, saddle nose; Slight onychodystrophy compared
Dysplasia (Christ-Siemens- AD/AR: NEMO hypo-/anodontia, peg-shaped to hidrotic disease
Touraine syndrome) conical incisors and canines

Hypomelanosis of Ito Not inherited; mosaicism Scoliosis, limb length Strabismus, hypertelorism
(Incontinentia pigmenti discrepancy; anodontia
achromians)

Hypothyroidism Plummer’s nails (onycholysis)

Incontinentia Pigmenti (Bloch- XLD: NF-κB essential Anodontia, peg/conical teeth; Strabismus, Coloboma,
Sulzberger’s) modulator (NEMO) Supernumerary vertebrae with Cataracts, Optic Atrophy
extra ribs

Juvenile Xanthogranuloma Hyphema, Hypopyon

(JXG)

KID Syndrome (Keratosis- AD and AR: GJB2 Keratitis (secondary blindness Dystrophic
ichthyosis-deafness) (encodes connexin 26) may occur)

Lamellar Ichthyosis AR: transglutaminase 1 Ectropion

(TGM1)

LEOPARD Syndrome AD: PTPN11 (encodes Growth retardation Hypertelorism Koilonychia

(Moynahan) SHP2)

Lichen Planus Dorsal Pterygium

Linear Morphea Melorheostosis

Lipoid Proteinosis (Urbach- AR: extracellular matrix Sickle-shaped beanbag Eyelid “String of Pearls”
Wiethe) protein 1 (EM1) calcifications in hippocampus

Lymphedema-distichiasis AD: FOXC2 Distichiasis (double row of

Syndrome eyelashes) --> corneal irritation;
ectropion

Maffucci’s Syndrome Sporadic but now also Enchondromas,

parathyroid hormone chondrosarcoma, short stature
receptor protein defect
(PTHrP)

Mal de Meleda AR: secreted Ly-6/uPar Koilonychia; subungal

related protein 1 (SLURP1) hyperkeratosis

Marfan’s Syndrome AD: fibrillin-1 Marfanoid habitus: tall, Upward lens displacement Dolionychia
arachnodactyly, pectus
excavatum, high arched palate,
kyphoscoliosis

McCune-Albright Syndrome Sporadic; postzygotic Polyostotic fibrous dysplasia

somatic mutations in
GNAS1

Menkes Kinky Hair Syndrome XLR: MKN or ATP7A Occipital horns (exostosis),
(Occipital Horn Syndrome) (encodes ATPase - copper frontal bossing, wormian bodies
binding) in sagittal suture, metaphyseal
widening with spurs in long
bones

Monilethrix AD: human basic type II Teeth abnormalities Cataracts (rare) Brittle
hair keratin genes (hHb1/
KRT81, hHb6/KRT86)

Multicentric Mutilating arthritis, accordion

Reticulohistiocytosis hand

Multiple Endocrine Neoplasia AD: RET proto-oncogene Marfanoid habitus

(MEN III AKA IIb)

D­Rirections
in
esidency p. 3 • Winter 2002
 boards’ fodder
Bones, Eyes, and Nails
With contributions from Elise M. Herro, MD, Benjamin A. Solky, MD, and Jennifer L. Jones, MD. (Updated July 2015*)

CONDITION INHERITANCE: GENE BONE EYES NAILS

Multiple myeloma Absent lunulae

Nail-Patella Syndrome (HOOD) AD: LMX1B Posterior iliac horns, Absent Lester iris (hyperpigmentation Triangular lunula, micronychia,
patella of pupillary margin), cataracts, anonychia
glaucoma

Neurofibromatosis I (NF-1) AD: NF1 (encodes Sphenoid wing dysplasia, Lisch nodules (iris hamartomas), Macronychia
[Von Recklinghausen] neurofibromin scoliosis optic gliomas, congenital
glaucoma

Neurofibromatosis I (NF-2) AD: NF2/SCH (encodes Juvenile posterior subcapsular

[Bilateral acoustic schwannomin/merlin) lenticular cataracts
neurofibromatosis]

Oculocutaneous Albinism OCA 1 - AR: tyrosinase Blue to gray-blue irides (OCA1)

(OCA) (TYR) Blue to yellow brown irides
(OCA2/3),
OCA2 (most common) - nystagmus, photophobia,
AR: P gene prominent red reflux, impaired
visual acuity
OCA3 - AR: tyrosinase
related protein 1

Osteogenesis Imperfecta AD: genes encode type I Fragile bones (fractures) Blue sclera
collagen Type I: bowing of long bones,
kyphoscoliosis
Type II: beaded ribs, crumpled
humeri and femora, abducted
thighs

Pachydermoperiostosis AD (1/3) Periarticular and subperiosteal Clubbing

(PDP) [Primary hypertrophic periostosis
osteoarthropathy]

Pachyonychia Congenita I Type I - AD: K16/K6a Thickened nails, pincer nails,

(Jadassohn-Lewandowsky staph/Candidal paronychia
syndrome) (fingers>toes)

Pachyonychia Congenita II Type II - AD: K17/K6b Natal teeth (N.B. oral benign Thickened nails, pincer nails,
(Jackson-Lawler) leukokeratosis in PC type 1) staph/Candidalparonychia
(fingers>toes)

Papillon-Lefèvre Syndrome AR: CTSC (encodes Tentorial & chondroid

cathepsin C) plexus dural calcification;
alveolar bone resorption and
loss of teeth

Progeria (Hutchinson-Gilford AD: lamin A Large cranium; frontal bossing, Thin, dystrophic
syndrome) thin beaked nose, micrognathia;
osteoporosis, coxa valga;
delayed permanent teeth

Pseudoxanthoma Elasticum AR (most common); Intracranial calcification Angioid streaks (rupture in

(PXE) [Gronblad-Strandberg] AD Bruch’s membrane), retinal
ATP-binding cassette hemorrhage causing blindness
subfamily C member 6
(ABCC6)

Psoriasis Oil spots, onycholysis, pitting

Refsum Syndrome (Phytanic AR: PAHX, PEX7 Salt & pepper retinitis
acid storage disease) pigmentosa

Renal Disease Lindsay’s Nails

Retinoids, Indinavir, and Pyogenic Granuloma

Estrogen

Rhizomelic Dwarfism Enchondromas

Richner-Hanhart Syndrome AR: tyrosine Variety skeletal anomalies Pseudoherpetic keratitis, corneal
(Tyrosinemia type II) aminotransferase ulceration, neovascularization
and blindness

Rubenstein-Taybi Syndrome Sporadic Broad thumbs and halluces, Strabismus Brachyonychia

AD proposed: human beaked nose
CREB-binding protein
(CREBBP)

Russell-Silver Syndrome Sporadic Short stature, clinodactyly of fifth

finger, skeletal asymmetry

Sarcoidosis Lytic bone cysts of hands with

honeycombed pattern

Schopf-Sculz-Passarge AR Hypodontia Cystic eyelids

Syndrome

Sjögren-Larsson Syndrome AR: fatty aldehyde Scissor gait Glistening dots

dehydrogenase (FALDH) retinitis pigmentosa

www.aad.org/DIR Winter 2002 • p. 4 D­Rirections

in
esidency
 boards’ fodder
Bones, Eyes, and Nails
With contributions from Elise M. Herro, MD, Benjamin A. Solky, MD, and Jennifer L. Jones, MD. (Updated July 2015*)

CONDITION INHERITANCE: GENE BONE EYES NAILS

Sturge-Weber Syndrome Sporadic Tram-track (gyriform) Ipsilateral glaucoma

(Encephalotrigeminal calcifications in temporal/
angiomatosis) occipital cortex; skeletal
hypertrophy a/w capillary
malformation

Systemic Sclerosis Resorption of distal phalanges Pterygium Inversum Unguis

(ventral)

Trichinosis, Endocarditis & Splinter hemorrhages

Trauma

Trichorhinophalangeal AD: TRPS1 Cone-shaped phalangeal Thin nails

Syndrome epiphyses; pear-shaped broad
nose

Tuberous Sclerosis AD or spontaneous Enamel pits; phalangeal Retinal hamartomas (phakomas) Koenen’s tumor (periungal
(Bourneville’s syndrome) TSC1: hamartin periosteal cysts; calcification fibroma), macronychia
TSC2: tuberin of tubers in basal ganglia,
subependymal nodules

Von Hippel-Lindau Syndrome AD: VHL tumor Retinal hemangioblastomas

suppressor

Waardenburg Syndrome AD Dystopia canthorum (not type II),

Type I: Pax3 heterchromia irides
Type II: MITF
Type III: Pax 3
Type IV: SOX1O and
endothelin-3

Wilson’s Disease AR: ATB7B (encodes Kayser-Fleischer ring (copper Blue lunulae
(Hepatolenticular ATPase CU2+-transporting deposit in Descemet’s
degeneration) polypeptide membrane)

Xeroderma Pigmentosum AR: XP (multiple variants) Photophobia, ectropion,

benign eyelid papillomas, BCC,
melanoma

X-Linked Ichthyosis XLR: arylsulfatase C/ Posterior comma-shaped

steroid sulfatase (STS) corneal opacities (Descemet’s
membrane)

Yellow Nail Syndrome FOXC2 Yellow curved nails, absent lunula/

cuticles

Reviewed and updated July 2015 by: Alina Goldenberg, MD, Emily deGolian, MD, and Sharon Jacob, MD.

D­Rirections
in
esidency p. 5 • Winter 2002