GOLTZ SYNDROME NSU-COM / LARKIN COMMUNITY HOSPITAL PRESENTERS: ANN R EED, DO, HYUNHEE PARK, DO, JULIE FREDERICKSON , DO. PROGRAM DIRECTOR: STANLEY SKOPIT, DO, MSE, FAOCD

Case presentation

 17 year old female with established diagnosis of Goltz syndrome presented to our office Jan. 2011 with c/o “Dry skin and itchy scalp”  PE: Syndromic facies w/ aniridia, microphthalmia, short stature, sparse hair, hypodontia, syndactyly, blaschko linear hyper and hypopigmentation, perioral papillomas, scaly scalp and xerotic skin  Dx: Xerosis Cutis , Seborrhea and alopecia in patient with Goltz  Tx: Ketoconazole 2% shampoo MWF alt with T/Sal Lidex solution BID x 2 weeks to scalp Cerave/Cetaphil to body Biotin 2500 mcg daily  Bx’s: 3/8/11 Shave biopsy (R labial commissure) - Verruca with candidiasis 3/22/11 Shave biopsy (L labial commissure) - Impetiginized Verruca with candidiasis Ketoconazole 2% cream BID given for topical treatment

Goltz Syndrome Overview Focal Dermal Hypoplasia or Goltz-Gorlin syndrome Rare Multiple abnormalities of mesodermal and ectodermal tissues First described by Dr. Goltz in 1962 Approximately 300 reported cases worldwide Inheritance X-linked dominant  90% female  Lethal in males with non-mosaic hemizygous mutations  10% affected individuals: males with genomic or functional mosaicism 95% of cases are sporadic Gene locus Xp11.23 Mutation in PORCN gene  lack of Wnt signaling Variability in clinical severity (lyonization) Goltz Syndrome Cutaneous Findings

Wu M-C et al. / Dermatologica Sinica 29 (2011) 59-62 Wang L et al. Focal dermal hypoplasia updates. Oral Diseases. 2014; 20:17–24 Goltz Syndrome Extracutaneous Findings Non Cutaneous features include: Facial abnormalities Skeletal features CNS features Ear, Dental and Ocular abnormalities Cardiopulmonary GI GU  Asymmetry of the face  Low-set protruding ears  Narrow nasal bridge and broad nasal tip with unilateral notch of the nasal alae  Pointed chin Colobomas, anophthalmia, microphthalmia, strabismus, nystagmus, and ectopia lentis Prognathism, agenesis or dysplasia of the teeth, delayed tooth formation/eruption, , irregular spacing and malocclusion, enamel defects, notching of the incisors or extra incisors. Osteopathia Striata

 Gastrointestinal features:  Genitourinary features: • Malrotation of the intestine • Abnormalities of the kidneys • Papillomatous lesions of the or ureters (eg, bifid ureter, esophagus leading to obstruction renal pelvis) • Gastric polyps • Gastric reflux with laxity of the • Horseshoe kidney hiatus • Hypoplastic or absent kidney • Diaphragmatic hernia • Omphalocele • Hernias, rectal prolapse, and perianal papillomas FOCAL Mnemonic Female gender Osteopathia striata Coloboma Absent ectodermis-, mesodermis-, and neurodermis-derived elements Lobster claw deformity Work-up  Chest x-ray: Costovertebral defects Diaphragmatic hernia  Eye examination: Colobomas  Abdominal MRI: Diaphragmatic hernia  Renal ultrasound: Structural anomalies of the kidneys and urinary collecting system  Hearing evaluation  consultation Pathology

 Reduction in dermal collagen  Telangiectasia  Adipocytes of varying sizes in upper dermis Labs  No associated lab abnormalities reported with this syndrome in > 350 journal articles searched on PubMed  Follow routine surveillance guidelines established for the general population Monitoring  Dermatologist – for painful and pruritic erosive lesions  Otolaryngologist – papillomas of the larynx  Dental – Every 6 months for enamel hypoplasia leading to dental caries  Physical/occupational therapy and Orthopedic surgeon – hand and foot malformations, etc.  Ophthalmologist – eye abnormalities Management  Supportive  Subspecialist referral Pulsed dye laser (telangiectasias)  Cryotherapy (giant papillomas)  Prevention of secondary complications  Genetic counseling Prenatal Diagnosis •Prenatal ultrasonographic findings variable: • Nonspecific fetal growth delay to specific organ and/or developmental anomalies • Contingent on the degree to which an individual is affected •Prenatal molecular genetic testing is possible for pregnancies at increased risk if the disease-causing mutation in the family has been identified: • Amniocentesis (15-18 weeks) • Chorionic villus sampling (10-12 weeks) Support Resources  National Foundation for Ectodermal Dysplasias www.nfed.org  Society www.ectodermaldysplasia.org Case presentation

 17 year old female with established diagnosis of Goltz syndrome presented to our office Jan. 2011 with c/o “Dry skin and itchy scalp”  PE: Syndromic facies w/ aniridia, microphthalmia, short stature, sparse hair, hypodontia, syndactyly, blaschko linear hyper and hypopigmentation, perioral papillomas, scaly scalp and xerotic skin  Dx: Xerosis Cutis , Seborrhea and alopecia in patient with Goltz  Tx: Ketoconazole 2% shampoo MWF alt with T/Sal Lidex solution BID x 2 weeks to scalp Cerave/Cetaphil to body Biotin 2500 mcg daily  Bx’s: 3/8/11 Shave biopsy (R labial commissure) - Verruca with candidiasis 3/22/11 Shave biopsy (L labial commissure) - Impetiginized Verruca with candidiasis Ketoconazole 2% cream BID given for topical treatment References

1. Alster TS, Wilson F. Focal dermal hypoplasia (Goltz's syndrome). Treatment of cutaneous lesions with the 585-nm flashlamp-pumped pulsed dye laser. Arch Dermatol. 1995 Feb. 131(2):143-4

2. Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology. 3rd ed. 2012. Elsevier Saunders. 2012: 951.

3. Calonje E. McKee's Pathology of the Skin, With Clinical Correlations. Saunders; 2012.

4. Castelo-Soccio L. Focal Dermal Hypoplasia Syndrome Clinical Presentation. Updated: Dec 16, 2014. Accessed on 08/25/15. http://emedicine.medscape.com/article/1110936-overview#a6.

5. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin Clinical Dermatology. 11th ed. Philadelphia: Elsevier. 2011: 565-566.

6. Liu J, Hsu PT, VanderWielen BA, Teng JM. Treatment of recalcitrant excessive granulation tissue with photodynamic therapy in an eight-year-old patient with focal dermal hypoplasia syndrome. Pediatr Dermatol. 2012 May-Jun;29(3):324-6.

7. Murakami C, De oliveira lira ortega A, Guimarães AS, Gonçalves-bittar D, Bönecker M, Ciamponi AL. Focal dermal hypoplasia: a case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(2):e11-8. References

8. Patterson JW, Ph.D. GA. Weedon's Skin Pathology. Churchill Livingstone; 2015.

9. Perioral and Genital Lesions. Copyright 2003-2006 by AOCD Grand Rounds. Submitted on: Mar 14, 2010, Accessed on 08/25/15

10. Purvis, D. Alkindi, S. Focal Dermal Hypoplasia (Goltz Syndrome). DermNet NZ. Accessed on 08/25/15 http://www.dermnetnz.org/systemic/goltz.html

11. Sakar S, Patra C, Das, A, Roy S. Goltz Syndrome: A newborn and skin lesions. Indian J Dermatol 2015;60:215

12. Sutton VR, Van den Veyver IB. Focal Dermal Hypoplasia. 2008 May 15 [Updated 2013 Apr 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov.ezproxylocal.library.nova.edu/books/NBK1543/

11. Wang L et al. Focal dermal hypoplasia updates. Oral Diseases. 2014; 20:17–24.

12. Wu, Meng-Chi et al. Focal dermal hypoplasia: report of a Taiwanese case. Dermatologica Sinica, Volume 29, Issue 2, 59-62