Constitutional pancytopenia can be seen in following except
Ans. b (Diamond-Blackfan syndrome) (Ref. Nelson Paediatrics 18th12047; Table 468-1)Diamond-Blackfan syndrome (DBS), also called congenital hypoplastic anemia, is a macrocytic pure red aplasia associated with several congenital anomalies such as short stature, webbed neck, cleft lip, shielded chest and triphalangeal thumbs. Therapy is mainly corticosteroids. For unresponsive patients, transfusion therapy is indicated.CONSTITUTIONAL (INHERITED) PANCYTOPENIA# It is defined as decreased marrow production of the 3 major hematopoietic lineages on an inherited basis, resulting in anemia, neutropenia, and thrombocytopenia.0# Constitutional pancytopenias account for approximately 1/3 of cases of pediatric marrow failure. 0# Fanconi anemia is the most common constitutional disorder. 0# Causes of constitutional pancytopenia:- Fanconi anemia- Shwachman-Diamond syndrome- Dyskeratosis congenital- Amegakaryocytic thrombocytopenia- Down syndrome- Dubowitz syndrome- Seckel syndrome- Reticular dysgenesis- Schimke immune-osseous dysplasia- Familial aplastic anemia (non-Fanconi)- Pearson syndrome- Noonan syndromeFanconi (Aplastic) Anemia# Fanconi's anemia is an autosomal recessive disorder characterized by progressive pancytopenia and macrocytosis. Cell fusion of Fanconi cells with normal cells or with cells from unrelated patients with Fanconi anemia produces a corrective effect on chromosomal fragility, a process called complementation. No other constitutional pancytopenia is associated with an abnormal chromosomal breakage study.0 The average age at diagnosis is 8 years.# The most common anomaly is Hyperpigmentation of the trunk, neck, and intertriginous areas, as well as cafe-au-lait spots and vitiligo, alone or in combination. Other associated deformities include microcephaly, microphthalmia, short stature, horseshoe kidneys and absent thumbs (not triphalangeal thumbs).# The most frequent solid tumors are carcinomas of the head, neck, and upper esophagus, followed by carcinomas of the vulva and/or anus and lower esophagus.# Hematopoietic stem cell transplantation is the only curative therapy for the hematologic abnormalities. Androgens produce a response in 50% of patients. Oral oxymetholone is used most frequently once a day. Low-dose prednisone orally every 2nd day may be added. Transposons are nonviral vectors that have been used successfully for gene delivery hold promise in humans.Shwachman-Diamond sxndrome (Autosomal recessive) - Essential diagnostic criteria are:# Exocrine pancreatic insufficiency# Variable hematologic cytopenias due to marrow failure.# Chromosomes are normal, and there is no increased breakage after DEB clastogenic stress testing.# The mutant gene SBDS maps to chromosome 7qll.Dyskeratosis congenita (DC)# Mucocutaneous and hematopoietic systems involved in association with somatic abnormalities.# The diagnostic ectodermal triad is:- Reticulate skin pigmentation of the upper body- Mucosal leukoplakia, and- Nail dystrophy.# DC is a constitutional pancytopenia; aplastic anemia occurs in approximately 50% of cases, usually in the 2nd decade of life. Patients also have a predisposition to cancer and MDS.# Approximately 85% of patients are male, compatible with X-linked recessive inheritance.# The X-linked recessive form of DC maps to Xq28.
Fanconi's anemia
Diamond-Blackfan syndrome
Dyskeratosis congenita
Schwachman Diamond syndrome
Blood