GAPO syndrome

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 2067

Definition

A multiple congenital anomalies (MCA) syndrome involving connective tissue characterized by Growth retardation, Alopecia, Pseudoanodontia and Ocular manifestations.

Epidemiology

Approximately 38 patients have been reported in literature since the first description in 1947.

Clinical description

Patients have a short stature due to post-natal growth retardation and a typical facies with high and bossing forehead, hypertelorism, puffy eyelids, midfacial hypoplasia, depressed nasal bridge, anteverted wide nostrils, thick everted lower lip, micrognathia, low-set ears and premature aging appearance mainly due to redundant hyperelastic skin with unusual wrinkles. Scalp hair may be primarily present but disappears after the first months of life leading to complete or partial alopecia. Eyebrows and/or eyelashes are sparse. Primary and permanent teeth are formed but fail to erupt. Ocular manifestations may include progressive optic atrophy, glaucoma, strabismus, megalocornea, myelinated retinal nerve fiber layer, bilateral keratoconus, nystagmus and ptosis. Otorhinolaryngologic features are choanal atresia, deafness and presence of flaccid and pulsatile masses with an audible murmur in the mastoid area associated with dilated and tortuous scalp veins. Patients have a mild intellectual deficit. Some patients have also been reported with umbilical hernia, hyperextensible joints, osseous anomalies (congenital dislocation of hips or delayed bone age) and cutaneous manifestations (hemangioma or depigmented areas). Other manifestations include intracranial hypertension in infancy, hypothyroidism, mitral valve dysfunction or cardiomyopathy, hepatomegaly, renal impairment and altered gonadal functions (irregular periods or amenorrhea, oligoastenospermia).

Etiology

Homozygous nonsense or splicing mutations in the ANTXR1 gene, encoding anthrax toxin receptor 1, also known as tumor endothelial marker 8 (TEM8) cause GAPO Syndrome.

Diagnostic methods

Diagnosis mostly relies on physical examination. Cerebral angiography and magnetic resonance angiography reveal prominent cortical veins, occluded or absent left transverse sinus, left sigmoid sinus, agenesis of left jugular vein, and enlarged veins underlying the palpable scalp masses. Skin biopsy may reveal dermis anomalies including amorphous hyaline substance and recently reported pyoderma vegetans.

Antenatal diagnosis

Antenatal diagnosis is not possible as features are not detectable by fetal ultrasound.

Genetic counseling

GAPO syndrome appears to have an autosomal recessive transmission pattern.

Management and treatment

There is no curative treatment. Management mostly relies on ophthalmologic surveillance and symptomatic treatment of the multiple health problems.

Prognosis

GAPO patients are reported to have a reduced lifespan (until their 4th -6th decade of life).

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