Focal Dermal Hypoplasia (Goltz Syndrome) with Mutations in PORCN

 

Synonyms: Goltz Syndrome, Goltz-Gorlin Syndrome

 

Chromosome: Xp11.23

Gene: PORCN (probable protein-cysteine N-palmitoyltransferase porcupine), which is the human analoge to the Drosophila porcupine

Mutations: loss-of-function or deletions

 

Inheritance: X-linked dominant

 

Key clinical features:

(1) skin manifestations

(1a) hypoplastic or atrophic areas of skin

(1b) hyperpigmented or hypopigmented areas

(1c) cutis aplasia

(1d) verrucoid papillomas of skin

(1e) abnormal nails (ridged, hypoplasia or aplasia)

(1f) sparse or absent hair (scalp, eyebrows, areas of abnormal skin)

(1g) telangiectases

(1h) yellow-pink fat nodules in the dermis

(2) limb malformations

(2a) oligodactyly

(2b) syndactyly

(2c) split hand and/or foot malformations

(2d) camptodactyly

(2e) reduction defects in distal long bones (radius, ulna, tibia, fibula)

 

Other findings:

(1) verrucoid papillomas of mucous membranes

(2) osteopathia striata (seen in bone on plain radiographs)

(3) abnormalities of costovertebral segmentation (bifid ribs, fused ribs, butterfly vertebrae, hemivertebrae)

(4) diastasis pubis

(5) facial anomalies (notched alae nasi, pointed chin, small underfolded pinnae)

(6) dental anomalies

(7) abdominal wall defect

(8) diaphragmatic hernia

(9) renal anomalies (horseshoe kidney, absent kidney)

(10) ocular abnormalities (microphthalmia, anophthalmia, coloboma)

(11) lacrimal duct abnormalities

(12) cleft palate

(13) brittle hair

(14) gastroesophageal reflux

(15) short stature

 

Complications:

(1) fibrous dysplasia of bone

(2) giant cell tumor of bone

 

Many patients are mosaic for mutations in PORCN. This can be difficult to detect and associated with false negative genetic testing.

 

Testing should include:

(1) sequence analysis

(2) search for large deletions (for females with no mutations found on sequence analysis)