Fanconi's Pancytopenic Syndrome or Pancytopenic-Dysmelia syndrome (Fanconi)

Guido Fanconi reported a familial syndrome of pancytopenia and congenital physical abnormalities at birth in three brothers in 1927. The association of skeletal abnormalities and progressive lethal pancytopenia was reported by Uehlinger in 1929 although the clinical features had been noted previously by Fanconi. The diagnostic hallmark is increased chromosomal breakage in response to DNA damaging agents like mitomycin C (MMC) or diepoxybutane (DEB). This is an autosomal recessive disorder involving all races and ethnic groups. The mean age at diagnosis is 7.9 years in males and 9 years in females.

Clinical presentation:- It is characterized by short stature, abnormal thumbs, microcephaly, cafe� au lait as well as hypopigmented spots and a characteristic facial appearance including broad nasal base, epicanthic folds and micrognathia. Haematological investigations reveal the underlying anemia and pancytopenia. The onset of anaemia is between 17 months to 22 years of age. Bleeding tendency is seen in many of these patients.

The skin is involved most frequently. Melanin deposits on the trunk, axilla, groin and neck occur in 74% patients. Skin manifestations are followed by poor growth, anomalies of the upper limbs, male hypogonadism and microcephaly.

The International Fanconi anemia Registry analysis of 370 patients found that nearly 40% had skeletal abnormalities. Upper limb anamolies involve the thumb most frequently with absence, hypoplasia, supernumerary, bifid or triphalangeal thumb. Absent or hypoplastic navicular bone or a greater multangular bone can also be seen. Radii are absent or hypoplastic. In Fanconi�s anaemia if radii are affected, thumb is always abnormal, while in thrombocytopenia absent radii (TAR) syndrome radii are absent and thumb is always present. Anamolies of radial component of upper extremity are strongly suggestive Fancon�s anemia

Underdevelopment of genitilia is seen in 40% of male patients, followed frequently by undescended testes.

Most common abnormalities of the eye include micropthalmia (in 20%) and strabismus while deafness and structural abnormalities are associated with ear defects.

Renal anomalies occur in 30% of patients and these include renal aplasia, ectopia, or horseshoe kidney.

Low birth weight, failure to thrive and mild or moderate dwarfism are the other common manifestations.

Less common defects include congenital heart disease, gastrointestinal anomalies and a variety of others.

Leukemia is a frequent complication in these Patients.

In conclusion, it is advised that all children with radius or thumb deficiency, regardless of the severity, should undergo a renal ultrasound, echocardiogram, and complete blood count to evaluate the potential for associated systemic conditions; which include Fanconi�s anemia, the Holt-Oram syndrome, the VATER (vertebral anomalies, anal atresia, tracheoesophageal fistula, esophageal atresia, renal agenesis) syndrome or VACTERL ( vertebral anomalies, anal atresia, cardiac abnormalities, tracheooesophageal fistula, renal agnesis, and limb defects) association.