Identical Twins with Infantile Systemic Hyalinosis: Case study and review of literature.
BACKGROUND
Infantile Systemic Hyalinosis (ISH) is a rare and fatal genetic disorder with mutations in Capillary morphogenesis gene-2 CMG2 / Human anthrax toxin receptor gene-2 ANTXR2 resulting in spindle cell proliferation, altered collagen metabolism with extensive deposition of amorphous eosinophilic PAS positive hyaline material in the connective tissues of various organs. The common presenting features would be progressive stiffness of multiple joints, skin lesions, multiple episodes of protracted infections, prolonged diarrhoea and failure to thrive. ISH is a rapidly progressive painful disorder of infancy with a very short life expectancy.


METHODS
3 months old identical twins born to a 5th degree consanguinous couple were brought with complaints of excessive cry, deformity of all four limbs, recurrent episodes of respiratory tract infections and diarrhoea since birth. Evaluation of both the probands revealed facial dysmorphism with perinasal nodules, gingival hypertrophy, fixed deformities of multiple joints bilaterally, umbilical hernia, fleshy perianal nodules and pigmented patches over knuckles and ankle. A clinical diagnosis of ISH was suspected and confirmed by detection of homozygous c.277_278insATTATTT (or p.L93Yfs*14) in exon 3 of the ANTXR2 gene. The probands were managed symptomatically and parents were counselled regarding prenatal diagnosis in future pregnancies.


CONCLUSIONS
IHS is commonly misdiagnosed as Arthrogryposis Multiplex Congenita and is often mismanaged with manipulation of the stiff joints and invasive surgical procedures. Prenatal diagnosis by chorionic villus biopsy is possible once causative mutation in a family is identified. Invasive surgical interventions for histopathological analysis can be avoided as clinical features are most often classical and genetic analysis is confirmatory. Management is conservative and symptomatic. We report this case of identical twins with features of ISH in view of its rarity as timely clinical suspicion can avoid painful and invasive procedures for diagnosis and management.
Department of Medical Genetics, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad and Adjunct Faculty, Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad. India.
Maheshwar Lakkireddyl Shagun
ML
Aggarwal
Department of Orthopaedics, Nizam's Institute of medical Sciences, Punjagutta, Hyderabad. India.
Vijaykrishna
V
Chilakamarri
Department of Geneticist, Center for Medical Genetics, Mumbai. Maharashtra. India.
Vasundhara S
VS
Chennuri
Bio-Chem, Sr. Resident, Gandhi Hospital, Hyderabad. India.
Madhulatha
M
Karra
Anthrax toxin receptor; Capillary morphogenesis gene; Fleshy perianal nodules; Gingival hypertrophy; Hyaline deposition; Key Words: Consanguinity