Rajab-Spranger syndrome is an extremely rare autosomal recessive disorder, characterized by low birth weight, generalized failure of subcutaneous fat deposition, sensorineural deafness, short stature, intellectual deficit, and skeletal abnormalities. By school age, progeroid facial changes, due to atrophy of the 'fatty balls of Bichat', can also be observed. Skeletal abnormalities include narrowing of the tubular shafts of the long bone with relative widening of the ends of the bones, progressive osteopenia, delayed maturation, and late-onset dense metaphyseal striations in the distal femur, ulna, and radius. Characteristics common to other forms of lipodystrophy, including organomegaly, hirsutism, acanthosis nigricans, and metabolic abnormalities are lacking in this condition.
Only three cases with this condition have been reported in medical literature. All three belong to the same ethnic community.
Rajab et al. (2003) reported two brothers from a consanguineous family and a female from the same tribe with a congenital generalized lipodystrophy syndrome that differed from other known ones. Case 1 was born with low weight, had delayed developmental milestones, and was sensorineurally deaf by the age of three years. He had a history of two tibial fractures after trivial injuries, developed nocturnal seizures, and bouts of bulimia. At the age of 20-years, he was short with a flexed posture, and thin with absence of subcutaneous fat. His face was gaunt with hollowed cheeks, pinched nose, and deep set eyes. The limbs were thin with narrow wrists and ankles, knock knee, and cubitus valgus, and the muscles of the shoulder and pelvic girdle were prominent, but not hypertrophied. Hepatosplenomegaly, acanthosis nigricans, and hirsutism were absent. Neurologically, he had normal muscle power, reflexes, and no cerebellar signs with normal visual acuity. His cognitive development was equivalent to that of a seven-year-old child. Investigations revealed normal male karyotype, normal hormones, lipid profiles, alkaline phosphatase, serum calcium, creatinine and normal urine analysis as well as normal DNA synthesis after ultraviolet exposure test. Ultrasonography of the abdomen and echocardiography were normal. Skeletal X-rays showed narrowing of the diaphyses of long bones with relative wide undermineralized metaphyses, progressive osteopenia, delayed maturation, and peculiar dense longitudinal metaphyseal striations in the distal femur, radius, and ulna. MRI of the brain showed prominent cortical sulci. His sibling was 15-years when seen and had the same progressive history, clinical examination findings, and similar skeletal X-ray changes. Parents of these brothers were normal as well as the other four siblings, but the father had a slightly gaunt face. Case 3, on the other hand, was a female from the same tribe as the above mentioned patients. She had a low birth weight and at the age of two years was failing to thrive, with slow mental development, and was sensorineurally deaf. When seen at the age of seven and a half years, she was thin, short, with prominent facial creases on grimacing, with thin limbs, and narrow wrists and ankles, but prominent large joints of normal mobility. Her cognition was that of a three-year-old child. She had the same skeletal changes on X-rays as the brothers as well as the prominent cortical sulci in CT brain scan, with the other investigations being normal. Since all the patients had normal consanguineous parents, Rajab et al. (2003) concluded that this disorder might follow an autosomal recessive mode of inheritance. They also ruled out the possibility of SHORT syndrome, due to the different facial appearance and the absence of Rieger anomaly and joint laxity, as well as Cockayne Syndrome, due to the normal recovery of DNA synthesis after exposure to UV light, and absence of characteristic eye and skin changes. Rajab et al. (2003) concluded that the condition was a novel, heretofore undescribed genetic disorder.