Goltz Syndrome

Complex mesoectodermal hereditary disorder characterized by focal dermal atrophy, with herniation of fat-producing multiple papillomas, in association with skeletal, dental, ocular, and other anomalies.

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Focal Dermal Hypoplasia (FDH). [NB: Avoid confusion with Goltz-Gorlin syndrome (inheritable disease characterized by multiple cutaneous nodules with a tendency to become malignant).]

Frequency is approximately 2:100,000 newborns.

95% sporadic. X-linked dominant with in utero lethality in males or by a sex-limited dominant gene of variable expressivity. Gene is located on Xp22.31. Only 10% of cases occur in males (possibly the result of half-chromatid mutations).

The underlying molecular defect in FDH is not clear. Based on the common findings of syndactyly, oligodactyly, and polydactyly, the fetal expression of FDH is postulated to occur before week 8 of gestation because the hands and feet have differentiated and developed separate and elongated digits by the eighth week. Because skin and bone lesions generally follow the lines of Blaschko, mosaicism with random X-chromosome inactivation is probable. Clinical abnormalities indicate a profound dysplasia of ectodermal, neuroectodermal, endodermal, and mesodermal elements. Various in vitro observations of fibroblasts from lesional skin reveal abnormal growth kinetics of fibroblasts (increase in the fibroblast doubling time), abnormal glycosaminoglycan metabolism (decreased accumulation of hyaluronic acid), and absence of basement membrane type IV collagen. A hypothesis that aberrant dermal fibroblast growth and altered collagen fibers may be the basis of the skin defects in FDH has been suggested.

Usually female gender. Characteristic skin findings are present at birth (streaky areas of hyperpigmentation, atrophy, and telangiectasia and groups of soft, yellow-red nodules). Radiologic examination shows longitudinal striation of the long bones with crossing of the epiphyses (osteopathia striata). The combination of split-hand with syndactyly and absence of rays, the so-called lobster-claw hand, is a striking feature of the disorder.

Patients with areas of total absence of skin at birth have been reported. More commonly, skin changes are usually present at birth or develop shortly thereafter from erythematous areas. Papillomas usually develop later, involving the mucous membranes or skin. Lesions of the oropharynx and peritonsillar regions have been described. Laryngeal papillomas requiring tracheostomy in one case and esophageal papillomas associated with strictures have been described. In addition, anomalies involving the hands (syndactyly, polydactyly, camptodactyly, missing digits or entire hand), skeleton (hypoplasia or aplasia or the truncal skeleton), mouth (lip papillomas, hypoplastic teeth), and eyes (coloboma of iris and choroid, strabismus, microphthalmia) have been present in some cases. Gastroesophageal reflux, short stature, and mental retardation occur in many patients. Course and prognosis dependent upon the type and severity of noncutaneous involvement. Treatment is symptomatic. One case report describes a stillborn girl with Goltz syndrome who had truncus arteriosus II with hypoplastic pulmonary vasculature (arteries and veins) and lungs, massive diaphragmatic hernia and absence of one kidney.

Look for stridor and signs of increased work of breathing. Fiberoptic examination may be required to determine whether verrucous lesions in the hypopharynx and supraglottic larynx are obstructing visualization of the vocal cords during direct laryngoscopy and tracheal intubation. Evaluate the respiratory system in the presence of kyphoscoliosis (arterial blood gas analysis, chest radiographs, pulmonary function tests). If kyphoscoliosis is significant, echocardiography may be indicated (cor pulmonale).

Difficult cooperation in the presence of mental retardation should be expected and sedative/hypnotic premedication as well as the presence of the primary caregiver for induction of anesthesia may be helpful. Careful positioning is needed to protect the atrophic or absent skin areas. Thermoregulation may be impaired in patients with large areas of involvement. Monitoring of the body temperature and precautions to prevent hypothermia are necessary. General anesthesia with spontaneous respiration may be complicated by persistent partial upper airway obstruction secondary to supraglottic lesions. Tracheal intubation may be difficult as a result of these growths and the presence of facial abnormalities. Hypoplastic, anomalous teeth may be more prone to damage during direct laryngoscopy. Spinal and epidural anesthesia might be difficult because of spinal abnormalities (kyphoscoliosis). Frequent gastroesophageal reflux may require rapid-sequence induction. Secondary to the skin and anatomical anomalies, vascular access may be difficult.

Muscle relaxants should be avoided until the airway has been secured.

Microphthalmia with Linear Skin Defects (MLS) Syndrome: Some similar features, but associated with a deletion of the tip of the X chromosome; all main features are confined to the neck and head.

Osteopathia Striata with Cranial Sclerosis: Severe bone dysplasia in which osteopathia striata is associated with cranial sclerosis, dysmorphic facies, cleft palate, deafness, heart defects, and vertebral anomalies with variable expression. Neurologic findings range from normal development to psychomotor retardation and hydrocephalus.

Adams-Oliver Syndrome (AOS): Very rare inherited disorder characterized by defects of the scalp associated with multiple scarred and hairless areas that usually have dilated blood vessels directly under the skin. Scalp defects are present at birth. The extremities are either short (hypoplastic fingers and toes) or characterized by absent hands and lower legs. Congenital heart defects must be ruled out.

Aplasia Cutis Congenita: Most often inherited disorder with circumscribed or more extensive skin lesions that may also involve underlying tissues. Neurologic and cardiac anomalies have been described in these patients.

Delleman Oorthuys Syndrome: Multiple congenital anomaly syndrome mainly affecting the central nervous system, eyes and skin.

Epidermolysis Bullosa: Group of inherited bullous disorders characterized by blister formation in response to mechanical trauma.

Johanson-Blizzard Syndrome (JBS): Polymalformative syndrome characterized by nasal alar hypoplasia (beak-shaped), scalp defects, hypothyroidism, pancreatic achylia, and congenital deafness.

Setleis Syndrome: Puckered periorbital skin, absent or multiple rows of eyelashes.