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GENE/01(P) THE CHILD SYNDROME: CONGENITAL HEMIDYSPLASIA WITH
ICHTHYOSIFORM ERYTHRODERMA AND LIMB DEFECTS
Preena Uppal ; Premila Paul; Rohit Arora; SS Uppal; Suruchi Bajaj
Department of Paediatrics, Safdarjung Hospital, New Delhi
[email protected]
Introduction: The term CHILD syndrome is proposed as an acronym for congenital hemidysplasia
with ichthyosiform erythroderma and limb defects.It is a rare subtype of epidermal nevus
syndromes . CHILD syndrome caused by deficiency of 3beta-hydroxysteroid-delta8, delta7isomerase.The syndrome is characterized by unilateral erythema and scaling, with a distinct
demarcation in the middle of the trunk. . In addition, ipsilateral hypoplasia o of the skeleton, as
well as defects of the brain and the viscera are found. The ratio of females to males is 19:1.
Apparently, the CHILD syndrome is genetically determined. Arguments are presented in favor of
the hypothesis that the condition is due to an X-linked dominant gene lethal in hemizygous males.
Case report : A 6 year old male child,born of non consanguineous marriage presented with
multiple asymmetric deformities. The child had right sided hemihypertrophy . Cranial asymmetry
- a larger right lateral ventricle , right sided tonsillar enlargement with axial myopia in the right
eye with obvious facial asymmetry was present .Unilateral scaly lesions with distinct midline
demarcation were present .Kyphoscoliosis with genu valgum deformity and digital hyperplasia of
the opposite side was seen. We report this case as the child presented with hemihyperplasia , and
contralateral hyperplasia of the digits . CHILD Syndrome usually has ipsilateral defects .Only very
few cases of bilateral involvement have been described so far.
GENE/02(O) BETA KETOTHIOLASE DEFICIENCY: A CASE REPORT
Sindwani A, Jerath N, Sibal A
Apollo Centre for Advanced Pediatrics Indraprastha Apollo Hospital New Delhi
[email protected]
Beta ketothiolase deficiency is a rare autosomal recessive metabolic disorder of ketone body and
Isoleucine metabolism characterised by normal early development and recurrent episodes of
ketoacidosis in late infancy. Biochemically it is characterized by severe ketoacidosis, normal
glucose, mild to moderate hyperammonemia and characteristic urinary organic acid profile. Long
term prognosis is favorable if detected and managed early. This report describes one child with
Beta ketothiolase deficiency presenting with an episode of acute gastroenteritis followed by severe
ketoacidosis and shock. A Seven month old boy born to nonconsanguineous parents presented
with vomiting and loose stools for 72 hrs followed by lethargy and dyspnoea. Past history revealed
normal motor and social development and no similar episode. He was treated elsewhere with IV
sodabicarbonate and volume replacement, but acidosis worsened and he went into shock and coma
requiring ventilatory support and was transferred to our centre. Laboratory investigations revealed
blood pH=6.69, HCO3=3.1 mmol/L, Lactate=2.8 mmol/L, glucose=114 mg/dL, ammonia= 298
mmol/L. urinary analysis showed 4+ ketones, nil sugar. Child was kept on mechanical ventilation
and inotropic support. As the acidosis was persisting, peritoneal dialysis was started which
corrected acidosis in 12 hrs. He was subsequently put on protein and fat restricted diet, Carnitine
and Riboflavin supplementation. Urinary amino acid profile was normal. Urinary organic acid
analysis showed raised level of 2- methyl 3- hydroxybutyrate, triglyglycine and 2methylacetoacetate suggestive of Beta ketothiolase deficiency. He developed complications of
ventilator associated pneumonia requiring ventilatory support and gradual weaning over 3 weeks.
He was successfully extubated and was discharged on low protein diet and Carnitine and
Riboflavin. He is at present symptom free and being followed up.
GENE/03(P) DOWN SYNDROME AND THYROID DYSFUNCTION
Ritu Gupta, Ravinder K. Gupta
Department of Physiology, Govt. Medical College, Jammu (J&K)
[email protected]
Objective: To study the clinical spectrum of thyroid dysfunction in Down Syndrome Patients.
Design: Prospective Study Settings: Pediatric Clinic Material and Methods: About 30 children
who met the phenotypic criteria for establishing the diagnosis of Down syndrome were enrolled
for the study. Besides clinical features of Down syndrome, they were looked for all clinical signs
of hypothyroidism. Besides maternal age, the age, sex, socio-economic and educational status
were recorded. Relevant investigations pertaining to hypothyroidism were performed which
included X-ray for assessment of bone age, serum cholesterol, ECG and thyroid profile (Serum
T3, T4 & TSH levels). Results: The males had definite preponderance (M:F 1.5 :1). The children
ranged from 9 month to 12 years (mean age being 3.4 years). The maternal age at the time of birth
of child ranged from 25 to 36 years with majority of children were born to 32-36 years age group.
About 33% were first in order, 20% each 2nd and 3rd in order and rest 27% were either 4th or 5th
in order. Upslanting palpebral fissure (100%), depressed nasal bridge (96%), prominent epicanthal
folds (92%) small open mouth (80%), fissured and protruding tongue (72%), low set ears (72%),
clinodactyly (64%), high arched palate (60%), wide gap between first and second toe (54%), flat
occiput (54%), single transverse palmar crease (48%) etc. were most common obvious features in
these children. Generalised hypotonia (80%), lethargy (60%), dullness (50%), rough and dry skin
(40%), constipation (27%), delayed motor milestones (17%) delayed mental milestones (15%),
etc. were the other presenting features. Three children gave a history of prolonged neonatal
jaundice while one child has undergone surgery immediately after birth for imperforate anus.
Wide and persistent open anterior fontanelle was seen in 8 cases. Decreased bone age
(radiologically) was seen in about 10 cases. The mean T3, T4 and TSH values were 138 ng/ml, 8.7
micro g /ml and 5.4 mu/L. Twelve children (40%) had increased levels of TSH (twice done from
different laboratories) with normal or decreased T3 and T4 levels. Other investigation like serum
cholesterol in such cases was raised above normal values in 7 cases. ECG was of low voltage type
in 3 such cases. Conclusion: About 40% children had increased levels of TSH revealing
hypothyroidism. It seems that hypothyroidism is common in Down Syndrome children. Though it
requires larger studies, a trial of thyroid replacement therapy (L. thyroxin) can be tried in such
cases which can improve the overall mental and physical growth.
GENE/04(O) GLUTARIC ACIDURIA TYPE I-IS IT PREVENTABLE CAUSE OF
GLOBAL DEVELOPMENTAL DELAY?
Shabu Bhahuleyan, Nutan Kamath, Rathika Shenoy, Kamalakshi Bhat
Department of Pediatrics Kasturba Medical College , Mangalore
[email protected]; [email protected]
Glutaric aciduria type I (GA-I) is an autosomal recessive metabolic disorder of lysine and
tryptophan metabolism caused by absence or marked decreased activity of the mitochondrial
enzyme glutaryl coenzyme A dehydrogenase. The clinical manifestations of GA-I usually develop
during first two years of life. We report a 14 month old male child whose timely diagnosis and and
treatment for GA-I helped to avoid irreversible neurological damage asssociated with the disease.
CASE REPORT- A 18 month old male child born of a non- consanguineous marriage to a primi
mother with uneventful pregnancy and labour presented with developmental delay and progressive
increase of head size. In the physical examination there was macrocephaly with head
circumference more than 95th centile for age, appropriate weight and length for age and motor
delay. In the initial workup, biochemical parameters were normal. CT scan brain showed cerebral
atrophy with prominent frontotemporal CSF spaces and batwing appearance of bilateral sylvian
fissures suggestive of Glutaric acidemia type I. Arterial blood gas and blood ammonia was normal
but blood lactate mildly elevated. Blood and urine done for metabolic screening by Tandem Mass
Spectroscopy showed Glutaric aciduria type I with severe carnitine deficiency. Hence the child
was put on low protien diet with supplementation of carnitine and riboflavin. Presently the child is
26 months with head circumference at the 90th centile for age and gaining milestones. Hence early
diagnosis and treatment avoided the irreversible neurological damage associated with the disease.
GENE/05(P) CLINICAL PROFILE OF OCULO-AURICULO-VERTEBRAL SPECTRUM
–A CASE SERIES
Deepika Harit, Pooja Dewan, Piyush Gupta.
27/63,Street No. 8, Vishwas Nagar, Delhi-110032
[email protected]
Introduction: oculo-vertebral spectrum (OAVS) refers to three rare disorders that are believed to
be intimately related to one another and which represent the range of severity of the same disorder.
These disorders are apparent at birth (congenital). It involves malformations of the eyes, ears and
spine. Oculo-auriculo-vertebral disorder (OAVD) represents the mildest form of the disorder,
while Goldenhar syndrome presents frequently as the most severe form. Hemifacial microstomia
appears to be an intermediate form. We had 7 patients 4 males and 3 females. All had unilateral
deformed ear along with ipsilateral LMN VII nerve palsy. Patients’ age varied from 15 days-2 yrs
at presentation. Only 2 cases had anotia, rest all had microtia. External ear opening was not
present in 3 cases. Right half of the face was involved in 5 cases and in 2 left side was involved. 2
children had absent kidney in the affected half of body. Echocardiography revealed VSD in one
patient, TOF in 1 patient and normal study in 4. Dermoid cyst in eyes was present in only one
patient, all other had normal eyes. 5 cases had normal spine and only 1 had spina bifida. CT scan
of ears done in 2 children and it was normal study. Hearing was found to be normal in all babies.
GENE/06(P) CLEIDOCRANIAL DYSPLASIA
Kalpana Dixit, Ramakant Dixit, Sidharth Sharma
Samarpan Child Clinic & Department of Respiratory Medicine, J L N Medical College, Ajmer
[email protected]
Introduction: Cleidocranial dysplasia is a rare disorder of autosomal dominant inheritance that
causes disturbance in the growth of bones of the cranial vault, the clavicles, the maxilla the nasal
and the lachrymal bones and the pelvis. Multiple supernumerary and impacted permanent teeth are
also commonly seen. Case report: A four year old female child presented with history of short
stature, fracture on minor trauma and delayed mile stones. She had dismorphic features i.e.
abnormal facies with low set ear, open anterior fontanelle, frontal bossing, bowing of limbs, flat
foot, Harrison sulcus, lordosis, hypotonia and high arched palate etc. His investigations revealed
hemoglobin 11.8 gm%, serum creatinine 0.5 mg%, serum calcium 10.1 mg%, serum phosphate 6
mg%, serum sodium 143 meq/l, serum potassium 5 meq/l, and normal liver function tests. Skeletal
survey revealed severely hypo plastic clavicles seen only in lateral aspect, barrel shaped chest cage
and spina bifida at upper dorsal vertebrae. There were no other bony abnormalities. 24 hour urine
calcium was 53.76 mg, phosphorus 139.4 mg and creatinine 98.16 mg% Tissue trans glutaminase
antibody, Ig A level was 13.88 EU/ml. His growth hormone level were slightly reduced although
thyroid profile was normal Conclusions: Cleidocranial dysplasia is an uncommon disorder,
however, its clinical and radiological manifestations are characteristic. Although benign disorder,
it carries with it several medicolegal implications in terms of complications. Management must be
tailored specifically to the patient needs.
GENE/07(O) FAMILIAL CROSSED POLYSYNDACTYLY
Pooja Dewan, Nitin Agarwal, Preeti Dewan
Departments of Pediatrics, Surgery and Anaesthesia, University College of Medical Sciences And
Guru Teg Bahadur Hospital, Delhi
[email protected]
"Polysyndactyly" describes both webbing and the presence of an extra number of fingers or toes.
Polydactyly of the thumb or the great toe, is classified as preaxial polydactyly, while of the little
finger, is called postaxial polydactyly. Affection of the three central digits is referred to as central
polydactyly. Coexistence of preaxial polydactlyly of the hand and and postaxial polydactyly of the
foot or vice versa, in association with presence of syndactyly is called “crossed polysyndactyly”.
We observed an extremely rare form of polysyndactyly affecting 7 members over four generations
in an Indian family. A term baby girl delivered in our hospital was found to have polysyndactyly
of the hands and feet. A detailed history revealed polysyndactyly in the previous three generations,
both in males (4) and females (3). In five members, (grandfather, mother, aunt, uncle, female
neonate) over three generations, physical examination was possible. In two, (greatgrandfather and
his only son) a detailed family history suggested all the clues to the diagnosis. There was no
history of consanguineous marriage in the family. Cutaneous syndactyly was seen in the hands and
feet of all members. Polydactyly was hexadactyly in all members except one who had
septadactyly. The affection was mostly bilateral with both the sides being mirror images of each
other. Four of the members underwent corrective surgery for cosmetic reasons. All members were
screened for renal anomalies by ultrasound examination, but were found to be normal. All the
members had normal facies, normal stature and normal intelligence. The pattern of inheritance
appears to be autosomal dominant with complete penetrance and variable expressivity.
GENE/08(O) PYRUVATE KINASE DEFICIENCY
Rajiv Kumar
E - 03, Housing Complex, Batra Hospital, New Delhi – 110062
[email protected]
INTRODUCTION: Erythrocyte pyruvate kinase (PK) deficiency is a rare and incurable genetic
disorder. It is a rare cause of neonatal hyperbilirubinemia. We report an infant with neonatal
hyperbilirubinemia due to PK deficiency. The initial approach involved rapid evaluation,
phototherapy and close monitoring of serum bilirubin levels. CASE REPORT: A sick newborn
referred to tertiary level NICU of our hospital with history of meconium stained liquor and
respiratory distress at 6 hours of life. He was born to a multigravida mother at term, weighing 2.9
Kg, by normal vaginal delivery following an uneventful pregnancy and labor. There was no
significant antenatal history. There was past history of intrauterine death. On examination, he was
sick, tachypneic and had mild pallor with icterus. The heart rate was 110/minute; respiratory rate
was 64/minute with recession. Intrauterine congenital infections, G-6-PD deficiency and pyruvate
kinase deficiency were suspected. Laboratory investigations revealed Hb 8.1 gm%, TLC
24,230/cmm with 73% neutrophils, 24% lymphocytes, 2% monocytes and 1% eosinophils, ESR
58 mm, reticulocyte count 45% and platelet count 80,000/cmm. PT and PTT were normal.
Malarial thick and thin smears were negative. Total and conjugated serum bilirubin was 14.9 mg%
and 4.8 mg% respectively. Liver enzymes were elevated. Serum electrolytes were normal.
Serological tests for VDRL, syphilis and HIV were negative. Hepatitis B surface antigen and
hepatitis C antibody were negative. CMV IgG and HSV IgG were positive. G-6-PD level was
normal. He was evaluated for hemolytic disease of newborn. Direct and indirect Coomb’s test was
negative. He developed jaundice and double volume exchange transfusion done on first day of life.
Post-exchange laboratory investigations revealed Hb 10.4 gm%, total serum bilirubin 6.4 mg%,
conjugated serum bilirubin 2.7 mg% and serum calcium 10 mg%. He was started on intravenous
fluids, IV antibiotics; packed cells transfusion and intensive double surface phototherapy were
given. He was discharged after 7 days of admission. At the time of discharge, the infant was
clinically better and there was mild icterus. Total and conjugated serum bilirubin was 5.8 mg%
and 2.1 mg% respectively; Hb 13.6 gm% and reticulocyte count 26%. He was tolerating feeds
well. A quantitative pyruvate kinase screening was done at age of 2 months, which was low. The
child was diagnosed as a case of PK deficiency. The child is regularly followed-up. The prenatal
diagnosis of PK deficiency in the family was made by direct DNA analysis which describes
diagnosis of a novel homozygous mutation in PKLR gene that subsequently helped the family in
the next pregnancy.
GENE/09(P) JEUNE’S SYNDROME OR ASPHYXIATING THORACIC DYSTROPHY
Santosh Kondekar, Keya Lahiri, Rajwanti Vasvani, Suresh Patil
Department of Pediatrics, Seth G S Medical College and KEM Hospital Mumbai 400012
[email protected]
Introduction: Jeuene syndrome is a potentially lethal rare autosomal recessive congenital dwarfism
characterized by typical skeletal dysplasia. We report a case of Jeuene syndrome with a family
history. Case details: A four month old male child born out of second degree consanguineous
wedlock with bad obstetric history was brought by parents with repeated episodes of fever, cough
and breathlessness since neonatal age. Patient was fullterm section delivery for nonprogressive
labor. He was the only living child out of total four gestations. The first gestation was terminated
following diagnosis of skeletal dysplasia on antenatal sonography in second trimester. Second
gestation was aborted spontaneously. Third gestation gave birth to a child with skeletal
deformities and child expired in first week of life. All gestations were extensively monitored
during antenatal period. Patient had achieved social smile and partial rollover. On examination
child had tachypnea with abdominal respiration, with chest retractions. His anthropometry was
suggestive of failure to thrive with short lower segment dwarfism. He had small bell-shaped
thorax with reduced diameters with micromelia of the limb and short digits. On respiratory
examination, he had bilateral crepitations. Rest of the systemic examination was normal.
Radiology showed bell-shaped small thorax with reduced diameters; short and horizontal ribs.
There were short square iliac wings, flat acetabular margin, short phalanges, metacarpals,
metatarsals. All this micromelia is consistent with Jeune’s syndrome. Colour Doppler of heart was
normal. Renal functions were normal. Child was discharged after 3 days of artificial ventilation
and antibiotic course. Discussion: Jeune syndrome like other thoracic dystrophies has a stormy
lethal course. Most children die of respiratory or renal failure. Only a few variants may survive.
Characteristic chest appearance is crucial in suspecting thoracic dystrophies.
GENE/10(P) MEHMO SYNDROME - A RARE X-LINKED DISORDER - A CASE
REPORT
Uma Raju, Harmeet Singh Arora, Kirandeep Sodhi, Ravi Ramamurthy, Vishal Puri
Dept of Pediatrics, Command Hospital, Pune
[email protected]
13 months old male child, third product of second degree consanguineous marriage, with normal
elder siblings & no family history of obesity, presented with history of excessive weight gain since
birth, generalized seizures since 5 months of age & global developmental delay. No significant
antenatal, perinatal & neonatal history. Born to non-diabetic mother through caesarian section with
the birth weight of 3.70 Kg. No history suggestive of congenital hypothyroidism. On examination
blood pressure - 92/58 mm Hg (<90th centile for age) , weight 15.5 kg ( > 97th centile for age),
length- 77 cm, head circumference – 42 cm ( <3rd centile for age), mid arm circumference- 17 cm.
Other features included generalized obesity, broad forehead with mild frontal bossing, flat
occiput, closed anterior fontanelle, chubby cheeks, large ear lobule, high frontal hairline,
hypertelorism, strabismus, downward deviation of mouth, thick lips, short neck, acral
edema(mild), bilateral talipes equines varus & micropenis. Testes were palpable inside the
scrotum. Neurologically, patient had generalized hypotonia, increased generalised bulk, decreased
vision in both eyes, bilateral convergent squint, with preserved pupillary reflexes & normal other
cranial nerves. Other systemic examination revealed no abnormality. Detailed ophthalmologic
evaluation revealed decreased vision in both eyes & bilateral convergent squint with no structural
anomaly. Investigations - normal T3/T4/TSH (on 2 occasions), blood sugar(R) – 114mg%, serum
cholesterol – 248 mg%, serum electrolytes within normal range, normal USG abdomen & X ray
spine. EEG showed features of diffuse encephalopathy. Chromosomal studies( Fluorescent-in-situhybridisation) were negative for any deletions / microdeletions (done to rule out other possible
causes of obesity ). Parents refused consent for muscle biopsy. Patient was discharged on oral
antiepileptics after satisfactory control of seizures & advised for physiotherapy & regular follow
up in OPD. Final diagnosis of rare MEHMO syndrome(Mental retardation, Epileptic seizures,
Hypogonadism and hypogenitalism, Microcephaly, Obesity and Hypotonia) was entertained after
further ruling out close differential diagnoses including hypothyroidism, Angelman syndrome,
Pradder Willi syndrome, Soto’s syndrome, Turner/Noonan’s Syndrome, Beckwith Weidman
Syndrome , Smith-Lemli-Opitz syndrome, Fragile X syndrome & Bordet Beidl syndrome.
GENE/11(P) OSTEOGENESIS IMPERFECTA TYPE III: CASE REPORT OF THREE
SIBLINGS.
Karuna Thapar, Naresh Jindal,Alok Kumar Goyal
Department Of Paediatrics, Government Medical College & Hospital Amritsar (Punjab)
[email protected]
Osteogenesis imperfecta (OI), also known as Brittle Bone Disease, is a heritable disorder of
connective tissue. Its hallmark feature is bone fragility, with a tendency to fracture from minimal
trauma or from the work of bearing weight against gravity. In the more severe forms of the
disorder, the bones are deformed as well as fragile.According to Sillence et al, 4 types have been
described, out of which Type-II is lethal in infancy, however, Type-III can have a full life span.
No information available regarding exact prevalence, however, in U.S., estimated to be 1 / 20000
live births. We are reporting three siblings of this disease due to its rarity. Case report: Three
siblings 7 year old female, 10 year old male and 12 year old female were brought to us for
progressive bowing of legs and multiple bone fractures. Perinatal history uneventful and
development normal till 4 -5 years of age. Father and mother were short statured but didn’t have
any fractures. On examination, a wide open anterior fontanelle , flat mid-face , frontal bossing,
multiple fractures involving both clavicles, Humerus, femurs, tibias, pectus carinatum of chest
wall, exaggerated metaphyseal flaring at wrist with slender diaphysis, scoliosis and slight bluish
sclera were seen. Children were short statured and macrocephalic. There was no hearing loss and
neurological examination was normal. Radiological examination has shown multiple bone fracture
with loss of bone mass, also popcorn appearance at knee joint was seen. They were classified as
Type-III OI according to Sillence classification.
GENE/12(P) ORAL ALENDRONATE IN OSTEOGENESIS IMPERFECTA : A REPORT
OF 2 CASES
Karuna Thapar, Naresh Jindal,Ira Dhawan
Department Of Paediatrics, Government Medical College & Hospital Amritsar (Punjab)
[email protected]
Osteogenesis imperfecta (OI) is a heritable disorder characterized by either a reduction in the
production of normal type I collagen or the synthesis of abnormal collagen as a result of mutations
in the type I collagen genes. There is no effective medical treatment for OIs. Bisphosphonates are
synthetic analogues of pyrophosphate that inhibit bone resorption by their action on osteoclasts.
Recently, beneficial effects of intravenous pamidronate treatment are reported in OI. Not much
data are available regarding oral alendronate treatment alone in children with OI. We report 2
cases of OI responded favourably to oral alendronate. Case report: Three siblings 7 year old
female, 10 year old male and 12 year old female were brought to us for progressive bowing of legs
and multiple bone fractures. They were classified as Type-III OI according to Sillence
classification. 7 year old female was having severe bronchopneumonia and CCF probably due to
immobility from a long time and was given intensive care treatment for the same. Other two were
treated with oral alendronate at a dose of 5 mg per day. They were administered pills 30 minutes
before the breakfast and asked to stay in upright position for an hour after the dose. At the end of
the 6 months of treatment, both children have tolerated well with no side effects. No new fracture
reported. Both cases were lost from further follow up. Conclusion: The usage of oral
bisphosphonates is inexpensive and easy to administer instead of intravenous form in cases of OI.
We conclude that oral alendronate treatment should be offered to all children with OI for better
quality of life.