Thalassemia major in a child with Dubowitz syndrome

Abstract

To the Editor: Dubowitz syndrome (DS) is an autosomal recessive disorder of growth retardation, microcephaly, mental retardation, and eczema 1 with a variable phenotypic spectrum. It also involves the skin, eyes, teeth, musculoskeletal, urogenital, cardiovascular, and immune systems 1. The diagnosis is based on the characteristic phenotypic features. Although, various hematological [aplastic anemia 2 acute lymphocytic leukemia 3] and malignant disorders [lymphoma 4, neuroblastoma 5, embryonal rhabdomyosarcoma 6] are associated, hemoglobinopathies has never been reported with DS. A 3½ month male was the first born to healthy unrelated parents at term gestation. The antenatal period was uneventful. At birth the child had a weight of 3 kilogram (kg) (z-score −0.73), Occipitofrontal circumference (OFC) was 36 centimeter (cm) (z-score 1.21) and the length was 50 cm (z-score 0.06). At 3 1/2 months the weight was 3.5 kg (z-score −4.62), length 55 cm (z-score −3.17) and OFC 39 cm (z-score −1.30). There was no significant family history. The child had a high sloping forehead, sparse eyebrows, hypertelorism, telecanthus, blephropimosis, left sided ptosis, left nasolacrimal duct blockage, flat and broad nasal bridge (Figure 1A), low set posteriorly angulated ears, high arched palate, left hand simian crease, clinodactyly, bilateral partial cut syndactyly of second/third toes with overlapping crowded toes (Figure 1B). The systemic examination including joints, skin, and genitalia were normal. The diagnosis of DS was considered on the basis of the phenotypic features. Thyroid function tests, lipid profile, karyotype, and FISH analysis were within normal limits. Five millimeter osteum secundum ASD was detected on echocardiography. Chromosomal breakage studies did not show any spontaneous or induced breaks. At 5 months of age there was increasing pallor and hepatosplenomegaly. The hemoglobin was 5.5 g peripheral smear showed microcytic hypochromic anemia, teardrop cells and nucleated RBC's. MCV was 57 fl. Hemoglobin electrophoresis by HPLC (high performance liquid chromatography) was suggestive of TM (HbF = 78%; HbA2 = 3%; HbA = 19%). Both parents were found to have thalassemia trait with presence of 619 bp deletion in the father and IVS 1–5 in the mother. The child was a compound heterozygote with both the mutations. Clinical photographs of the child. A: Facial appearance. Note sparse eyebrows, hypertelorism, blephropimosis, left sided ptosis, flat and broad nasal bridge. B: Feet of the child with cutaneous partial syndactyly of the second and third toes with crowded overlapping toes. Our patient had typical findings of DS. Absence of eczema and cryptorchidism does not rule out DS since this is seen in only 60% and 18% cases, respectively 1. There is no laboratory confirmatory test for DS. Neither the gene location nor the pathogenesis is yet known. Chromosomal breakage (spontaneous or after clastogenic stress) 7 and defects in cholesterol biosynthetic pathway or transport have also been reported 8. Sister chromatid exchanges have been shown to be normal 1. Whether this represents a chance association in a family with high carrier rate of thalassemia or is an associated gene defect is unclear.