The portal for rare diseases and orphan drugs

The total birth prevalence in Europe has been estimated at 1/500,000. Over 150 cases have been described to date.

Newborns often have a low birth weight with a small head and body size. Facial appearance is characteristic with narrow or triangular shaped head and high or sloping forehead, flat supraorbital ridge, scanty lateral eyebrows, short palpebral fissures, blepharophimosis, ptosis, abnormally modeled ears, broad and flat nasal bridge, micrognathia and unusual configuration of the mouth. Sumucous cleft palate is common. Other findings include cutaneous ezema, high-pitched or hoarse voice, hypospadias and cryptorchidism. Skeletal abnormalities in DS include sacral dimple, and clinodactyly (5th fingers), with cutaneous syndactyly of toes or fingers. Intellectual deficit is mostly mild to moderate. Furthermore a variety of ocular and dental abnormalities, such as hyperopia, cataracts, tapetoretinal degeneration, strabismus and taurodontia, anodontia/hypodontia or hyperdontia have been reported. Behavioral characteristics may include hyperactivity with short attention span, impulsivity and shyness. The spectrum of manifestations of Dubowitz syndrome may also comprise: hematological (aplastic anemia) and congenital heart defects, frequent infections, chromosomal instability and developement of malignancies (acute lymphoblastic leukemia or neuroblastoma; see these terms).

The etiology of Dubowitz syndrome has not been evidently elucidated. Two causal genes have been put forward in separate isolated cases and include NSUN2 and LIG4. However due to the large phenotypic overlap of Dubowitz syndrome with other clinical entities, there remains uncertainty on the etiology.

Diagnosis is based on the multiple clinical manifestations and is commonly made in early childhood.

Differential diagnosis includes fetal alcohol syndrome, Bloom syndrome, LIG4 syndrome and Fanconi anemia (see these terms).

Prenatal growth retardation may be observed on ultrasound but does not lead to a reliable prenatal diagnosis.

In some families, Dubowitz syndrome appears to have an autosomal recessive transmission. However, it has been suggested recently that Dubowitz syndrome is a microdeletion/microduplication syndrome rather than an autosomal disorder.

Growth, dental speech, behavioral and intellectual development and a general health status check should be monitored regularly and treated appropriately. Eczema and recurrent infections require conservative treatment. Surgical intervention might be necessary for certain cardiovascular, urogenital, craniofacial or limb anomalies. Surveillance of hematological and malignant disorders is recommended.

The prognosis is very variable depending on the severity and types of congenital anomalies present and the long-term outcome still remains elusive, as no data is available after puberty.