Microcephaly With Chemotactic Defect And Transient Hypogammaglobulinemia

Say et al. (1986) reported 2 brothers with microcephaly, dysmorphic facies, developmental delay, and hypoglobulinemia. Their facial similarity was striking, with sloping forehead, beaked nose, large and protruding ears, micrognathia, and high-arched palate. One brother had craniosynostosis. Both brothers had hypogonadism, flexion contractures, hypoplastic patellae, and scoliosis. They also showed low levels of serum gammaglobulins in infancy reaching normal levels by 3.5 years and 15 months, respectively. Defective chemotaxis and recurrent infections were present from the beginning and persisted to age of report, age 7 in the older brother. Carpenter et al. (1996) provided a brief follow-up of the patients reported by Say et al. (1986) at ages 18 and 19 years. Both boys had recurrent infections since birth, and they also developed skeletal changes consistent with multiple epiphyseal dysplasia and the autoimmune phenomena of recurrent panniculitis and erythema nodosum. Treatment with gammaglobulin every 3 weeks improved their condition. Linkage analysis showed that the brothers both inherited the same maternal alleles at Xp22.2-p21.2, suggesting X-linked inheritance.

Perandones et al. (1996) reported a 13-year-old boy with severe microcephaly, mental retardation, short stature, and recurrent infections. Dysmorphic features included a sloping forehead, metopic suture synostosis, abnormal hairlines, sparse eyebrows, hypertelorism, upslanting palpebral fissures, prominent nasal bridge, high-arched palate, irregular dental implantation, multiple caries, micrognathia, and low-set, posteriorly rotated ears. He also had flexion contractures of the limbs, ulnar deviation of the fingers with clinodactyly of the fifth fingers, dislocated hips, hypoplastic and displaced patellae, scoliosis, hypogonadism, cryptorchidism, and eczematous skin. Laboratory studies showed defective neutrophil chemotaxis. Perandones et al. (1996) suggested that this patient had the same syndrome as that described by Say et al. (1986).

Carpenter et al. (2000) stated that the 2 brothers reported by Say et al. (1986) developed macular degeneration and pigmented retinal lesions resembling retinitis pigmentosa. Laboratory studies showed normal IgG levels but IgG subclass deficiencies and decreased cellular immunity. Nijmegen syndrome (NBS; 251260), ADA deficiency (102700), cartilage-hair hypoplasia (CHH; 250250), and Lowry-Wood syndrome (226960) were excluded. Carpenter et al. (2000) suggested that their patients had the disorder reported by Roifman (1999) (300258). In a reply, however, Roifman (2000) noted several phenotypic differences and differences in specific immunodeficiencies between the 2 disorders and disputed that the 2 disorders were the same entity.