Indian J Pediatr DOI 10.1007/s12098-013-1307-1
SCIENTIFIC LETTER
Unusual Cause of Hypocalcemic Seizures in a Neonate Pooja Dewan & Shrishail Gidaganti & M. M. A. Faridi & Prerna Batra & Siddhnath Sudhanshu
Received: 22 July 2013 / Accepted: 11 November 2013 # Dr. K C Chaudhuri Foundation 2013
To the Editor: A term female neonate, a product of nonconsanguineous marriage, presented with multifocal seizures at 60 hours of life. Examination revealed micrognathia, deep set eyes, beaked nose, two small oral mucosal cysts, syndactyly in left hand, preaxial polysyndactly in left foot and widely separated cranial sutures. Investigations: ionized calcium 0.2 mmol/L (1.1– 1.4), serum calcium 6 mg/dL (9–10.5), serum phosphorus 8.7 mg/dL, alkaline phosphatase 670 IU. Seizures subsided with intravenous calcium gluconate. At 90 hours of life the infant had recurrent hypocalcemic seizures. Investigations: serum calcium 6.3 mg/dL, serum phosphorus 8.4 mg/dL, serum magnesium 1.7 mg/dL (1.5–2.5), serum parathormone (PTH) 0.5 pg/mL (15–68) and serum vitamin D3 1.9 ng/mL (30–100). Lumbar puncture, blood
Fig. 1 Cortical thickening and medullary stenosis of tibia and fibula (left), cortical thickening and decreased diploic spaces in cranial vault bones (right)
P. Dewan (*) : S. Gidaganti : M. M. A. Faridi : P. Batra : S. Sudhanshu Department of Pediatrics, University College of Medical Sciences and Guru Tegh Bahadur Hospital, Delhi 110095, India e-mail: [email protected]
culture and CT of the brain were normal. A normal echocardiogram and thymic presence on MRI of chest and absence of copy number gains or losses in DNA on Multiplex ligation-dependent probe amplification (MLPA) for 22q11.2 deletion syndrome excluded DiGeorge’s syndrome. Skeletal survey revealed cortical thickening and medullary stenosis of long bones and osteosclerosis of skull (Fig. 1). Characteristic radiographic features with hypoparathyroidism with dysmorphism enabled us to diagnose Kenny Caffey syndrome (KCS). There was no family history of similar illness. Genetic studies for tubulin chaperone E (TBCE) gene were not done due to financial and logistic constraints. The infant was discharged on oral calcium carbonate (100 mg/kg/d of elemental calcium) and vitamin D3 (0.25 mcg/d). At
Indian J Pediatr
2 mo the infant developed repeated multifocal seizures. Investigations: serum calcium 10.4 mg/dl, serum phosphorus 9.1 mg/dL, serum PTH 15 pg/mL. Electroencephalography suggested seizure disorder; MRI of brain revealed cortical atrophy. The seizures subsided with oral phenobarbitone therapy. At 15 mo age the infant had delayed language milestones with normocephaly. Transient hypocalcemia and hypoparathyroidism and radiographic abnormalities including medullary stenosis and cortical thickening are characteristic of KCS [1, 2]. A similar syndrome with autosomal recessive inheritance but with microcephaly designated as Sanjad-Sakati syndrome has been reported from the Middle East [2]. Together both are included in the spectrum of hypoparathyroidism, retardation and dysmorphism (HRD) syndrome. The inheritance of KCS is usually autosomal dominant/X-linked (KCS type 1) or rarely autosomal recessive (KCS type 2). Recessive KCS is associated with mutations in1q42-43 gene, TBCE gene [1, 3], 22q11 microdeletion [4] or chromosome 10p [5]. No gene has been localized for the autosomal dominant variant. Our patient had certain unique phenotypic features including oral cysts and polysyndactyly which may be included in the phenotypic spectrum of KCS.
Contributions PD and SG: Drafted the manuscript. All authors were involved in the patient management and approved the final manuscript. Dr. MMA Faridi will act as guarantor for this paper. Conflict of Interest None. Role of Funding Source None.
References 1. Khan AO, Al-Assiri A, Al-Mesfer S. Ophthalmic features of hypoparathyroidism-retardation-dysmorphism. J AAPOS. 2007;11: 288–90. 2. Diaz GA, Gelb BD, Ali F, Sakati N, Sanjad S, Meyer BF, et al. SanjadSakati and autosomal recessive Kenny-Caffey syndromes are allelic: Evidence for an ancestral founder mutation and locus refinement. Am J Med Genet. 1999;85:48–52. 3. Naguib KK, Gouda SA, Elshafey A, Mohammed F, Bastaki L, Azab AS, et al. Sanjad-Sakati syndrome/Kenny-Caffey syndrome type 1: A study of 21 cases in Kuwait. East Mediterr Health J. 2009;15:345–52. 4. Sabry MA, Zaki M, Shaltout A. Genotypic/phenotypic heterogeneity of Kenny-Caffey syndrome. J Med Genet. 1998;35:1054–5. 5. Sabry MA, Farag TI, Shaltout AA, Zaki M, Al-Mazidi Z, Abulhassan SJ, et al. Kenny-Caffey syndrome: An Arab variant? Clin Genet. 1999;55:44–9.
SCIENTIFIC LETTER
Unusual Cause of Hypocalcemic Seizures in a Neonate Pooja Dewan & Shrishail Gidaganti & M. M. A. Faridi & Prerna Batra & Siddhnath Sudhanshu
Received: 22 July 2013 / Accepted: 11 November 2013 # Dr. K C Chaudhuri Foundation 2013
To the Editor: A term female neonate, a product of nonconsanguineous marriage, presented with multifocal seizures at 60 hours of life. Examination revealed micrognathia, deep set eyes, beaked nose, two small oral mucosal cysts, syndactyly in left hand, preaxial polysyndactly in left foot and widely separated cranial sutures. Investigations: ionized calcium 0.2 mmol/L (1.1– 1.4), serum calcium 6 mg/dL (9–10.5), serum phosphorus 8.7 mg/dL, alkaline phosphatase 670 IU. Seizures subsided with intravenous calcium gluconate. At 90 hours of life the infant had recurrent hypocalcemic seizures. Investigations: serum calcium 6.3 mg/dL, serum phosphorus 8.4 mg/dL, serum magnesium 1.7 mg/dL (1.5–2.5), serum parathormone (PTH) 0.5 pg/mL (15–68) and serum vitamin D3 1.9 ng/mL (30–100). Lumbar puncture, blood
Fig. 1 Cortical thickening and medullary stenosis of tibia and fibula (left), cortical thickening and decreased diploic spaces in cranial vault bones (right)
P. Dewan (*) : S. Gidaganti : M. M. A. Faridi : P. Batra : S. Sudhanshu Department of Pediatrics, University College of Medical Sciences and Guru Tegh Bahadur Hospital, Delhi 110095, India e-mail: [email protected]
culture and CT of the brain were normal. A normal echocardiogram and thymic presence on MRI of chest and absence of copy number gains or losses in DNA on Multiplex ligation-dependent probe amplification (MLPA) for 22q11.2 deletion syndrome excluded DiGeorge’s syndrome. Skeletal survey revealed cortical thickening and medullary stenosis of long bones and osteosclerosis of skull (Fig. 1). Characteristic radiographic features with hypoparathyroidism with dysmorphism enabled us to diagnose Kenny Caffey syndrome (KCS). There was no family history of similar illness. Genetic studies for tubulin chaperone E (TBCE) gene were not done due to financial and logistic constraints. The infant was discharged on oral calcium carbonate (100 mg/kg/d of elemental calcium) and vitamin D3 (0.25 mcg/d). At
Indian J Pediatr
2 mo the infant developed repeated multifocal seizures. Investigations: serum calcium 10.4 mg/dl, serum phosphorus 9.1 mg/dL, serum PTH 15 pg/mL. Electroencephalography suggested seizure disorder; MRI of brain revealed cortical atrophy. The seizures subsided with oral phenobarbitone therapy. At 15 mo age the infant had delayed language milestones with normocephaly. Transient hypocalcemia and hypoparathyroidism and radiographic abnormalities including medullary stenosis and cortical thickening are characteristic of KCS [1, 2]. A similar syndrome with autosomal recessive inheritance but with microcephaly designated as Sanjad-Sakati syndrome has been reported from the Middle East [2]. Together both are included in the spectrum of hypoparathyroidism, retardation and dysmorphism (HRD) syndrome. The inheritance of KCS is usually autosomal dominant/X-linked (KCS type 1) or rarely autosomal recessive (KCS type 2). Recessive KCS is associated with mutations in1q42-43 gene, TBCE gene [1, 3], 22q11 microdeletion [4] or chromosome 10p [5]. No gene has been localized for the autosomal dominant variant. Our patient had certain unique phenotypic features including oral cysts and polysyndactyly which may be included in the phenotypic spectrum of KCS.
Contributions PD and SG: Drafted the manuscript. All authors were involved in the patient management and approved the final manuscript. Dr. MMA Faridi will act as guarantor for this paper. Conflict of Interest None. Role of Funding Source None.
References 1. Khan AO, Al-Assiri A, Al-Mesfer S. Ophthalmic features of hypoparathyroidism-retardation-dysmorphism. J AAPOS. 2007;11: 288–90. 2. Diaz GA, Gelb BD, Ali F, Sakati N, Sanjad S, Meyer BF, et al. SanjadSakati and autosomal recessive Kenny-Caffey syndromes are allelic: Evidence for an ancestral founder mutation and locus refinement. Am J Med Genet. 1999;85:48–52. 3. Naguib KK, Gouda SA, Elshafey A, Mohammed F, Bastaki L, Azab AS, et al. Sanjad-Sakati syndrome/Kenny-Caffey syndrome type 1: A study of 21 cases in Kuwait. East Mediterr Health J. 2009;15:345–52. 4. Sabry MA, Zaki M, Shaltout A. Genotypic/phenotypic heterogeneity of Kenny-Caffey syndrome. J Med Genet. 1998;35:1054–5. 5. Sabry MA, Farag TI, Shaltout AA, Zaki M, Al-Mazidi Z, Abulhassan SJ, et al. Kenny-Caffey syndrome: An Arab variant? Clin Genet. 1999;55:44–9.
