Goltz Syndrome - Cause, Clinical Symptoms, and Diagnosis

Introduction

Goltz syndrome is a rare genetic disorder that affects mostly females and has more severe symptoms than males. This disease is considered an X-linked dominant inheritance with male lethality, where the gene mutation occurs on the X-chromosome and can be passed down from mother to daughter but when passed down to the son, the fetus fails to survive in the womb. Father-to-son transmission is not reported in this syndrome. This occurs due to a mutation of the PORCN gene located in the X-chromosome arm Xp11.23. Individuals affected by this syndrome have features such as skin aplasia, congenital light or dark areas of skin color, malformed nails, digits that may be absent or webbed, pebbly skin, defects in enamel, absence of eye or malformed eye, facial asymmetry, scoliosis, short stature, epilepsy, and other abnormalities which are mentioned below in detail.

What Is Goltz Syndrome?

Goltz syndrome is a kind of ectodermal dysplasia, with an abnormality in the development of skin, nails, face, eyes, skeletal system, and brain. It is a hereditary genetic disorder that occurs mostly due to a mutation in the PORCN gene and usually affects females. It involves many clinical symptoms, and treatment is mainly supportive and symptomatic.

What Are the Causes of Goltz Syndrome?

Goltz syndrome occurs due to a mutation of the PORCN (porcupine O-acyltransferase) gene located in the X-chromosome arm Xp11.23. In 10 % of cases, it is caused due to mutation in HCCS, located on the long arm of chromosome 2q37.3, and TWIST2 genes, located on the short arm of X chromosome Xp22.2. The features of the PORCN gene include:

• The PORCN gene encodes a protein called WNT protein, which regulates cell growth during embryonic development.

• PORCN protein helps in transferring palmitoleic acid to WNT protein. Therefore the transfer of palmitoleic acid helps develop bone, skin, and other structures.

• Mutation in the PORCN gene causes the elimination of the PORCN protein, which helps in the formation of the WNT protein.

What Are the Clinical Symptoms of Goltz Syndrome?

The symptoms are often asymmetrical (different from the left and right sides).

Major Findings Include:

1. Skin, Nail, and Hair Manifestations:

• Congenital patchy skin aplasia (At birth, the skin is thin, and some areas are deprived of skin) and 90 % of patients are affected by this.

• Congenital light or dark areas of skin color.

• Soft Fat nodules which are yellow-pink, commonly present on extremities and the trunk.

• Nails are malformed, rigid, and small.

• Telangiectasias (blood vessels of the skin are thin and widened).

2. Limb Manifestations:

• Digits may be absent or webbed.

• Syndactyly (fusion of toes or fingers) affects 70 % to 90 % of patients.

• Ectrodactyly (split foot or hand).

• Oligodactyly (presence of a lesser number of fingers or toes).

• Transverse limb defect (absence of forearm, wrist, or elbow including acheiria [absence of hand] or hemimelia [absence or decreased bone length of upper or lower extremity]).

• Long bone reduction defect (decreased length of long bones).

Minor Findings Include:

1. Skin, Hair, and Nails Manifestations:

• Sparse, wiry, or absence of hair.

• Wart-like papillomas on the mucous membrane of the nose, mouth, esophagus, larynx, vaginal lining, rectal lining, or skin.

• Photosensitivity (extreme sensitivity when exposed to sun).

• Abnormalities in hair shaft such as a change in length, shaft, color, or density.

• Pebbly skin.

• Fat nodules and herniation.

• Pyogenic granuloma (raised bumps on the skin with increased blood vessels).

• Palmar and plantar hyperkeratosis (thickening of the skin).

• Hyperhidrosis (increased sweating).

2. Dental Manifestations:

• Defects in enamel.

• Missing teeth or presence of extra teeth.

• Peg teeth (tapering of the tooth).

• Deep fissures on the tooth.

• Multiple odontogenic keratocyst (cysts that affect the jaw).

3. Eye Manifestations:

• Small or absence of eyes.

• Notching of the retina and iris.

• Abnormal tear ducts.

• Cataracts (a cloudy area that covers the lens of the eye).

• Displaced lens.

• Optic nerve atrophy (damage to the optic nerve, which helps in vision).

• Nystagmus (involuntary movement of eyes).

• Strabismus (crossed eyes).

4. Craniofacial Abnormalities:

• Facial asymmetry.

• Microcephaly (small head).

• Low set ears.

• Notched skin of palate and nose.

• Cleft palate.

• Pointed chin.

5. Skeletal Abnormalities:

• Scoliosis (lateral curved spine).

• Giant cell tumors (noncancerous tumors which develop in the bone).

• Linear bone markings are seen in X-rays.

• Tiny collarbone and ribs.

6. Gastrointestinal Manifestations:

• Difficulty in swallowing and chewing.

• Gastroesophageal reflux.

• Defects in the abdominal wall.

• Constipation.

• Hernia (condition when a part of the organ is bulged out of its place because of weakened muscle and tissue which contains it).

7. Psychological Manifestations:

• Intellectual Disability.

• Cognitive disability (disabilities in communications, social skills, and self-help along with mental illness).

• Emotional lability (uncontrollable moods such as crying, laughing, irritability, or anger).

• Behavioral problems.

• Withdrawn behavior (difficulty in social activity involvement).

8. Neurological Manifestations:

• Seizures (neurological condition of sudden excessive activity of brain cells that causes abnormal activity).

• Sensorineural hearing loss (due to damaged inner ear).

Other Manifestations Include:

• Short stature.

• Weight faltering (poor weight gain).

• Small labia minora (folds of the opening of the vagina).

• Defects in the structure of kidneys such as renal agenesis, hydronephrosis, bifid (split) ureter, and horseshoe kidney.

• Congenital heart disease.

• Obstructive sleep apnea (occurs when the back muscles of the throat relax and cause it to narrow down or close the airway, which eventually stops breathing).

What Is the Diagnosis of Goltz Syndrome?

Diagnosis is based on clinical findings of the affected individual and molecular genetic testing for mutation of the PORCN gene. The molecular genetic findings include mutation or deletion of the PORCN gene. Affected males have somatic mosaicism (different genetic composition in two or more cell lines), and it is a postzygotic mutation (acquired during one’s life) and is not passed down. The molecular testing is done along with the combination of chromosomal microarray analysis (CMA), single-gene testing, and multigene panel.

Conclusion:

Goltz syndrome is an infrequent occurring genetic disorder that has many clinical symptoms which is because of a mutation in the PORCN gene, which hinders embryonic growth development. There is no definitive treatment; it is mainly supportive and symptomatic and involves many teams of professionals, such as dermatologists, ophthalmologists, pediatricians, nephrologists, ENT (ear, nose, throat) specialists, and other health professionals. Genetic counseling should be done since it is an X-linked dominant inheritance.