gene/06(p) - Indian Academy of Pediatrics

Mamta Muranjan, Rajkumar Agarwal, Suhas Bendrikar, Murlidhar Mahajan, Keya Lahiri.
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction: Nijmegen Chromosome Breakage syndrome (Berlin Breakage syndrome) is a rare
autosomal recessive disorder charecterized by chromosomal instability, sensitivity to radiation and a
strong predisposition to lymphoreticular malignancies. Genetic defect is a mutation of the NBS1 gene
on chromosome 8q21. Clinical diagnosis is established on the basis of characteristic clinical features,
namely severe growth failure, microcephaly, craniofacial dysmorphisms and associated visceral
malformations which were present in the case being reported.Diagnosis was confirmed by characteristic
findings on cytogenetic study. Case report: An 11 year old female child, Muslim by religion, born of
second degree consanguineous marriage, was under evaluation for growth stunting since three years of
age. She also had history of recurrent pyodermas since 4 years of age. She was operated for Patent
Ductus Arteriosus at the age of six months. Menarche was still not achieved. On examination, height
and weight were below the 5th percentile and microcephaly was present. Assessment of SMR by
Tanner’s staging was 1.There were no physical stigmas of any systemic disease accounting for the
severe growth failure. She had multiple macules all over the body resembling vitiligo and café-au-lait
spots were present. Thyroid profile was suggestive of hypothyroidism. In view of multisystem
manifestations, a chromosomal study was advised which revealed multiple chromosomal breakage and
fusion which was characteristic of Nijmegen chromosome breakage syndrome. The parents were
counselled about the inheritance and prognosis of the disease.
Keya R Lahiri, Parag M Tamhankar, Mamta Muranjan, Murlidhar Mahajan, Rajwanti K Vaswani
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction : The cardinal features of Noonan syndrome are unusual facies (ie, hypertelorism, downslanting eyes, webbed neck), congenital heart disease, short stature, and chest deformity. These patients
were previously thought to have a form of Turner syndrome, with which Noonan syndrome shares a
number of clinical features Case : 8 year old male child having patent ductus arteriosus with coarctation
of aorta was referred for delayed milestones . The child’s height was 113 cm for an expected of 127 cm.
The child had unusual facial features like microcephaly, lowset, large deformed ears, complete cleft
palate, antimongoloid slant, curly hair, short webbed neck, low hair line. He had bilateral undescended
testes.The chest showed pectus excavatum. Bone age was 4 – 5 years. There was profound bilateral
mixed hearing loss. He had moderate mental retardation. Conclusion: Any child suspected of having
Noonan syndrome requires a detailed cardiac workup. Approximately 25% of patients with Noonan
syndrome have mental retardation. The incidence of progressive high-frequency sensorineural hearing
loss may be as high as 50%. Recurrence risk for parents who do not appear to be affected or who have
only some facial features of Noonan Syndrome is 5%. Fertility in males with undescended testes may be
decreased hence the mother is more frequently the transmitting parent in familial cases. None of our
cases afforded the costly growth hormone therapy.
Ira Shah, Ashok Johari
Department of Pediatrics and Pediatric Orthopedics, B. J. Wadia Hospital for Children, Parel, Mumbai400012.
Background: Children with Osteogenesis Imperfecta (OI) suffer recurrent fractures resulting in pain,
deformity and disability. Various treatment forms have been tried for management of OI of which
bisphosphonates seem to have the maximum benefit in reducing fracture rate and improving bone
density. The role of intravenous pamidronate has been established in several studies. Also oral
alendronate also has shown promising results. We undertook this study for the first time in India to
determine the effect of oral alendronate in patients with OI in decreasing fracture rate and improving
bone density. Methods: A total of 11 patients with OI were referred for bisphosphonate therapy from
2002 to 2005. Patients were classified into various types of OI depending on the Sillence criteria. A
detailed clinical history such as number of fractures, family history and complete physical examination
was done. All patients underwent radiographic study and bone density measurement with baseline
biochemistry prior to start of medical therapy. Every patient was started on oral alendronate and
followed up for a period range of 2 months to 2 years. A retrospective analysis in pre and post treatment
change in fracture rate and bone density was done. Results: Of these 11 children, one was lost to follow
up and excluded from study and 3 have completed only 2 months of therapy. Pre treatment fracture rate
per year prior to treatment ranged from 0.5 to 6 with mean being 2.95 ± 1.57 and median of 2.5. The
fracture rate post treatment was 1.1 ± 0.59/year which was statistically significant (p = 0.0005). 7
children underwent Bone Mineral Density (BMD) analysis while on treatment and all had a rise in the
BMD, though not statistically significant. No significant change was seen in the serum biochemistries
and no child had an adverse effect to alendronate. Conclusion: Oral alendronate is effective for reducing
the fracture rate in patients with OI.
Mamta Muranjan, Parag M Tamhankar,Keya R Lahiri, Murlidhar Mahajan, Rajwanti K Vaswani
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction: Marfan syndrome is an autosomal dominant inherited disorder due to mutations in the
fibrillin-1 (FBN1) gene located on chromosome 15q21.1 leading to abnormal biosynthesis of fibrillin
glycoprotein that is the major constituent of connective tissue . Materials and methods: We evaluated
11 cases of Marfan syndrome that presented to us during the years 2003-2004. The differences in their
mode of presentation, age, sex, clinical features and treatment were studied. Results: There were 6
males and 5 females. The mean age at presentation was 13.91 yrs +/- 7.72. The youngest patient was 6
years old and the eldest was 30 years old. The most common presenting symptom was breathlessness [
6/11 cases] followed by chest pain[ 5/11 cases ] followed visual problems[4/11 cases].4 cases were
hospitalized cases [2 cases for spontaneous pneumothorax , 1 case for mitral valve prolapse with
congestive cardiac failure and one case for kyphoscoliosis for surgical correction. .6 patients had history
of pneumothorax. 4 cases had at least one affected parent .The following clinical features were observed
– arachnodactyly [ 10/11 cases], wrist sign [ 10/11 cases], thumb sign [ 10 / 11 cases], high arched
palate [ 9/11], hyper extensibility [ 5/11 cases], pneumothorax [ 4/11 cases], myopia [ 4/11 cases],
pectus excavatum [ 4/11 cases], pectus excavatum [ 4/11 cases], mitral valve prolapse [ 4/11 cases], lens
subluxation/dislocation [ 3/11 cases], pectus carinatum [ 2/11 cases], backache [ due to myelomalacia] [
2/11 cases] ,hernia [ 1/11 cases], scholastic backwardness [ 1/11 case] , kyphoscoliosis[ 1/11 cases],
cerebral aneurysm [ 1/ 11 cases]. Conclusion: Marfan syndrome is a clinical diagnosis, diagnosed on
basis of positive family history, arachnodatyly and various phenotypic features. Though the definitive
diagnosis is established by mutation studies, in clinical practice it may not be possible in all cases.
Rajwanti K Vaswani, Murlidhar Mahajan, Parag Tamhankar, Mamta Muranjan, Keya R Lahiri
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction : Klippel Feil syndrome Congenital anomaly of cervical spine characterized by a short
neck, low hair line and decreased range of neck motion. Type 1 is characterized by massive fusion of
the entire cervical spine. Type 2 is characterized by fusion of 1 or 2 vertebrae only. Type 3 occurs when
lumbar and thoracic spine anomalies are associated. Case3 year old male child presented with short
neck since birth. He had severe restriction in rotatory movement of the neck, low hair line and a
webbed neck. He could flex and extend his neck. The shoulders were elevated and there was a
limitation in abduction and external rotation of the arms. Synkinesia that is symmetrical movement of
both upper limbs was observed that is when the right elbow was flexed then the left elbow automatically
flexed. There were no signs of spinal cord compression, the power and reflexes were normal. The child
had delayed speech and could only babble. Examination of the thoracic and lumbar spine was normal.
No other systemic problems were detected.Diagnosis : Xray cervical spine clearly showed complete
fusion of all the cervical vertebrae. There was no atlantoaxial instability. Scapulae were bilaterally small
and elevated [Sprengel’s anomaly]. There was no omovertebral bone. USG abdomen did no reveal any
renal anomalies. Audiometry revealed bilateral sensorineural deafness. 2DECHO revealed no cardiac
anomaly.Conclusion : The etiology of this disease is unclear; it is probably due to failure of
segmentation in early fetal life. It is a challenge to discover the etiology of this disorder and devise
methods to treat it. A close evaluation of family members is indicated since autosomal dominant
inheritance is noted.
Monika Sharma, Inderpreet Sohi, Sunita Jacob
Christian Medical College, Ludhiana
A severely deformed freshly stillborn baby was delivered by a 24years old primigravida with
nonconsanguinous marriage at 35 weeks of gestation. Her antenatal ultrasounds had detected severe
IUGR and severe oligohydamnios ,which hindered the detection of gross malformations. The baby had
fused lower limbs with a single foot , a ruptured exomphalos, absent external genitals and anal opening
and a lumbar meningomyelocoel. Facial features were squashed and the upper limbs were normal.
Sirenomelia type 3 (two femurs and absent fibulae), sacral agenesis and complete spina bifida were
detected by an infantogram. Autopsy revealed hypoplastic lungs, hypoplastic left atrium, single
umbilical artery, a single multicystic dysplastic kidney on the right with absence of the rest of the
genitourinary tract (including absent internal gonads), few superficial cysts in the liver and with the gut
ending in a small pouch. Sirenomelia complex is an anomaly of uncertain etiogenesis. Its etiogenesis
has been compared with that of caudal regression syndrome (CRS) due the common feature of fused
lower limbs. Sirenomelia differs by the presence of a single umbilical artery and renal anomaliescommonly agenesis, which are not seen with CRS. We report a case with dysplastic cysts in the kidneys
and liver, which may be explained by a primary mesoblastic defect as postulated for CRS. Multicystic
renal dysplasia has been reported only once before, though a coexistence of hepatic cysts has not been
reported before. We report this case for its rarity and even rare association with cystic dysplasia of the
kidney and liver.
Keya R Lahiri, Parag M Tamhankar, Murlidhar Mahajan, Mamta Muranjan, Rajwanti K Vaswani
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction: Sturge Weber syndrome is a triad of facial portwine stain [ophthalmic nerve distribution],
ipsilateral cerebral vascular malformation and seizures. It is a defect in the distribution of the cephalic
part of neural crest cells, which migrate to the supraocular dermis, choroids and pia mater. Case : 6
month old infant presented with refractory generalized tonic clonic seizures since 2 months of age. He
had a red discoloration of skin of face and reddish/ greenish discoloration over a large area of the back
and scattered areas over the thighs. These were port wine stains .He was developmentally delayed with
only head control achieved at 5 months of age. Other siblings were unaffected. Child was investigated
in the form of CT scan brain which demonstrated dilated tortuous, calcified vessels in the left cerebral
hemispheres that were meningeal hemangiomata. Ocular examination revealed normal intraocular
tension and normal angle of the anterior chamber. No choroidal hemangioma were present. The child
required valproate in doses of 50 mg/kg/day for seizure control. Regular ophthalmologic examination
was advised. Conclusion : Portwine stains occur frequently in children without any ophthalmic or
neurological problems. Only patients with lesions involving the ophthalmic division of the trigeminal
nerve are at a risk of neuro- ocular complications. The seizures most commonly begin between 2 – 7
months of age. Cerebral calcification is not evident by radiography until later infancy, the earliest
occurring in 13 months of age. Generally the calcification is first noted in occipital region. These
features must be recognized in children with facial portwine stains and appropriately investigated.
Mamta Muranjan, Parag M Tamhankar, Rajwanti K Vaswani, Keya R Lahiri, Murlidhar Mahajan
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction : VATER is mnemonic for vertebral defects, anal atresia, tracheoesophageal fistula and
radial dysplasia. Nearly all cases have been sporadic with no recognized teratogen or chromosomal
abnormality. The VATER association was later expanded to VACTERL association [vertebral
anomalies, anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies and limb
anomalies]. Case 1: A 7 year old girl presented with acute onset breathlessness after a trivial fall. On
examination she had shortening of the forearm with radial deviation of the hand and absent left thumb.
There was quadriplegia with brisk reflexes. Spinal cord compression was suspected. Xray cervical spine
revealed os odonteum [fusion of the bodied of the C2, C3, and C4 vertebrae] with atlantoaxial
dislocation due to fracture of the peg of axis. MRI cervical sin confirmed the diagnosis. She was treated
with cervical traction. Ultrasound abdomen revealed single left kidney. She ultimately died of a
respiratory complication in the intensive care unit. Case 2: An 11 month old male child presented wirth
cyanotic congenital heart disease. On examination he had a hypoplastic right thumb. Xray thoracodorsal
spine anteroposterior view revealed a hemi-vertebrae at T2 level and butterfly vertebrae[T3 level].
2DECHO revealed double outlet right ventricle with ventricular septal defect with pulmonary stenosis.
Diagnosis: in each of the above 2 cases at least 3 elements of the VATER/ VACTERL association were
noted. Conclusion: Importance of the association is to identify this association early in life so that
severe /life threatening defects can be recognized early and treated. In routine well baby clinics and the
pediatric outpatient departments it is important to recognize these subtle defects and rule out an
association. Babies with VACTERL can otherwise live an almost normal and productive life.
Keya Lahiri, Suhas Bendrikar, Rajkumar Agarwal, Murlidhar Mahajan, Mamta Muranjan.
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction : Bowing of legs is a very common complaint in pediatric practice. Rickets is the first
clinical suspicion when it is seen in a growing child. However, when present in older children, skeletal
dysaplasis are more likely. One such disorder being reported is the Weismann-Netter-Stuhl syndrome. It
is a rare autosomal dominant inherited skeletal disorder. It is characterized by osseous dysplasia.
Affected individuals exhibit bowing of the tibia and fibula, although in some individuals, other bones
may also be affected. The primary characteristic of Weismann-Netter-Stuhl syndrome is short stature.
Approximately, 70 cases have been reported in the medical literature since the disorder’s original
description in 1954. Case History: A 7 year old male child, born of non-consanguineous marriage
presented with short stature and progressive bending of lower limbs since 3 and half years of age.
Examination revealed short stature with a height age of 4 years and a retarded upper segment to lower
segment ratio. Skeletal abnormalities noted were varus deformity of the leg, kyphoscoliosis, lumbar
lordosis and costochondral beading. Radiographs of the lower limbs revealed tibia vara, bowing of the
legs, cortical thickening and osteopenia. These changes were diagnostic of Weissman-Netter-Stuhl
syndrome. Parents were counseled about the nature of the disease.
Rajwanti K Vaswani, Mamta Muranjan, Parag M Tamhankar, Murlidhar Mahajan, Keya R Lahiri
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction: This syndrome consists of a triad of cutaneous vascular malformations, ipsilateral soft
tissue swelling and/or bone hypertrophy and venous varicosities. The lesions are a combined capillaryvenous-lymphatic malformation, which may be localized to one limb or could be widespread. Case: An
11-year-old girl presented with slow progressive enlargement and disfigurement of the right lower limb
with purplish red nodular textured raised lesions over the right lower limb and the chest. These were
cavernous hemangiomas, which had progressively increased in size from early infancy. The skin over
the hemangiomas was friable and bled easily. Both feet were massively enlarged [macrodactyly that is
disproportionate growth of the digits]. Colour Doppler of the limbs showed capillary-venous
malformation. Venography of the limbs showed absent deep venous system and hemangiomas in the
superficial system. Magnetic resonance angiography of the whole body did not reveal any visceral
hemangiomas. Conclusion : Most patients with this syndrome can be treated conservatively with
compression stockings. Venous varicosities recur after surgery in 90% of patients. Aspirin probably is
indicated in all patients with thrombophlebitis. Magnetic resonance angiography of the whole body may
reveal any visceral hemangiomas. Cavernous hemangiomas can enlarge rapidly, usually in the first year
of life, producing high-output congestive heart failure or a consumptive coagulopathy. Coagulopathy
(Kasabach-Merritt syndrome) is marked by anemia, thrombocytopenia, prolonged prothrombin time and
activated partial thromboplastin time , reduced fibrinogen levels, and fibrin split products.
Kausik Mandal, S. Aneja, Neelu Sharma, Anamita Khan, Sumanta Panigrahi
Department of Pediatrics and Dermatology, Kalawati Saran Children's Hospital, New Delhi -110001.
Pachydermoperiostosis is syndrome characterized by hypertrophic changes involving skin and bones.
Secondary causes (e.g. pulmonary and pleural malignancies) of this disorder are well known. Primary
pachydermoperiostosis is a rare developmental disorder manifested in children. Various modes of
inheritance are reported. In May 2004, a one and a half year old child was brought, to our hospital with
complaints of inability to stand, bowing of limbs and drumstick appearance of fingers and toes. He is a
product of a consanguineous marriage and is 4th of five siblings. He had an elder sibling who died of
malnutrition at 6 years, and a younger sibling who died of pneumonia at 4 months. Both the siblings
were females and had similar dysmorphology. On examination the child had a wide-open anterior
fontanel, apparent widening of lower end of both femurs and clubbing of fingers and toes. He also had
hyperhidrosis and restriction of movement of both knees. He was developmentally normal, except
delayed gross motor milestones. Rest of the systemic examination was normal. Biochemical parameters
of blood including calcium, phosphorous, alkaline phosphatase and total creatinine phosphokinase were
normal. Chest x-ray had revealed normal heart and lung shadows. Skeletal survey had shown lamellar
periosteal reaction in the shafts of long bones, with normal ends and articular surfaces.
Electrocardiogram and echocardiography were normal. VDRL of the patient and his parents were nonreactive. Ultrasonogram of abdomen was also normal. The diagnosis of primary hypertrophic
osteoarthropathy was made. We have explained the self-limiting nature of the disorder to the parents
and subjected the child to physiotherapy. The child is now two years and nine months old. He can walk
without support, though he still has some contractures of the knee joints. He has developed thickening
of skin of the fronto-temporal areas of the forehead. From the above features we have made the
diagnosis of “primary pachydermoperiostosis”. We were unable to find the exact cause of death of the
two female siblings and attributed it to associated social problems.
Rajwanti K Vaswani, Keya R Lahiri, Parag M Tamhankar, Murlidhar Mahajan, Mamta Muranjan
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction:Tuberous sclerosis is a genetic disorder affecting cellular differentiation and proliferation,
which results in hamartoma formation in many organs (eg, skin, brain, eye, kidney, heart).Case: A 9
year old female child with seizure disorder complained of acne. Skin of the face showed numerous
papules which were fibrous-angiomatous lesion varying in colour from flesh coloured to yellow
especially over the cheeks . The skin on trunk showed hypopigmented macules classified in to thumb
printmacules ; lanceolate macules ( one end rounded and the other end with a sharp tip)/ash leaf
macule, confetti macules tiny 1 to 3 mm macules, others include café-au-lait patches and fibromatous
plaques and nodules. The Woods lamp examination was negative. There were sclerotic and cystic
changes in phalangeal bones. Ctscan brain showed calcified nodules [tubers] in the cortex and white
matter especially in the periventricular white matter .Other hamartomas seen were lipomas , fibroma [
gingival and subungual ]; shagreen patches [goose-flesh like].Seizures :had started in early infancy and
were myoclonic in type which later on progressed to become generalized tonic clonic.patient had
normal intelligence. It has autosomal dominant inheritance however in this case the parents did not
show any signs. Conclusions: Most individuals present with parental concern about small raised tumors
on the child's face. Angiofibromas can be differentiated from acne vulgaris by telangiectasia, absence of
comedones and pustules, and a relatively asymptomatic nature Neurodevelopmental testing as ageappropriate screening for behavioral and neurodevelopmental dysfunction at the time of diagnosis is
essential . New MRI techniques such as FLAIR (fluid attenuated inversion recovery) help identify small
tubers, which may not be detected with other imaging techniques. Echocardiography is recommended
for patients of any age with symptoms of cardio rhabdomyoma. Because most symptoms occur in
infants, older children do not need to have an echocardiogram.
Naresh Kumar
J.B.M.M. Civil Hospital Amritsar
4.5 year old female child presented with occasional seizures since age of 4 months. The child remained
on different anticonvulsant. Seizures were lateralized to begin with, later became generalized. There
was no family history of seizures. There was no history of trauma, fever, eardischarge, vomiting, loose
motion etc. The child did not have any symptoms pertaining to heart, lungs and kidneys. The child was
first in birth order, full term, hospital delivered, with immediate cry at birth. Antenatal and perinatal
history was uneventful. Both motor and mental milestones were delayed. Immunization and feeding
history was satisfactory. On detailed examination, the child was malnourished (PEM grade II as per IAP
classification) with mild pallor. The child had hypopigmented skin lesions on the back (Photograph
no.1). Also a roughened raised lesion, light brown in colour with orange peel consistency was seen on
middle of upper part of back. There was present cataract in left eye (Photograph no.2). Systemic
examination was normal. Haemoglobin was 9 gm/dl. The peripheral blood film was within normal limit.
Blood sugar, serum calcium, phosphorus, liver function and renal function tests were with in normal
limit. X-ray chest was within normal limit. MRI brain revealed multiple cortical tubers. There was
slight reduction of white matter tracts with its delayed myelination. (Photograph no.3 & 4). Ultrasound
scan of left eye showed cataract with thickened chorioretina with retinal calcification. In view of clinical
details and MRI brain report, the child was diagnosed as a case of Tuberous Sclerosis. Parents were
advised to improve nutritional status. She was prescribed sodium valporate and haematinics. The
seizures declined drastically. The case is being reported for its rarity.
Ritu Gupta, Ravinder K. Gupta
Department of Physiology, Govt. Medical College, Jammu
Case: One week female, first in order was noticed to have swelling of both hands and feet since birth.
The baby was passing urine adequately. There was no history of fever, cough, refusal of feed, rash or
any abnormal movements. The baby was first in order and was born of non-consanguineous marriage.
The marriage has taken place almost a year back and age of mother at the time of birth was 25 years.
Antenatal period was uneventful. This full term baby was delivered pervaginally at home and the birth
process was uneventful. There was no significant family history of such complaints. On examination,
the baby was active, afebrile, with good cry and had normal physiological neonatal reflexes. The vitals
were maintained. Her weight was 2400 gms. length was 46 cms. and head circumference 34 cms. There
was no pallor, jaundice or cyanosis. There was pitting edema over dorsum of hands and feets and this
edema was not present on rest of the body. The baby had webbed and short neck and had low posterior
hair line. The chest appeared broad and had widely spaced nipples (both the nipples were outside
midclavicular line). The cardiovascular, respiratory and abdominal examination was clinically normal.
The baby underwent investigations. The hemoglobin was 17gm/dl, TLC-7500 / mm3, polymorhs-53,
lymphocytes-45 and monocytes 2. Routine urine and 24 hour urine for proteins were within normal
limits. RFT and LFT were also within normal limits. VDRL of mother and baby were negative. TORCH
test was normal. X-ray chest and skull did not reveal anything abnormal. The ultrasound of abdomen
was normal except that ovaries could not be localized. Echocardiography was normal. The baby was
subjected to karyotype analysis. Every well spread metaphase plate contained 45 chromosomes after
short term lymphocyte culture. The karyotype prepared from metaphase plates showed XO condition. In
view of clinical details and laboratory finding the diagnosis of TURNER’S SYNDROME was made.
The baby was managed symptomatically and followed. To conclude a strong possibility of Turner’s
syndrome should be kept in mind if a neonate presents with edema of dorsum of hand and feet.
Mamta Muranjan, Keya R Lahiri, Parag M Tamhankar, Rajwanti K Vaswani, Murlidhar Mahajan.
Genetic Division, Department of Pediatrics, Seth Gordhandas Sunderdas Medical College & K.E.M.
Hospital, Parel, Mumbai - 400012.
Introduction:Mucolipidosis is an inherited disorder of lysosomal enzymes phosphorylation and
localization. It presents in early infancy and death is usually by 5th – 8th year of life. Case A 20-monthold child presented with unusual facial appearance in early infancy and psychomotor retardation. He
had a direct inguinal hernia operated at 1 year of age. There was a history of repeated upper respiratory
tract infections.He had short stature, facial dysmorphism in the form of puffy eyelids, corneal clouding,
long philtrum, coarse facies, striking gingival hyperplasia. There was mild hepatomegaly. Joint
contractures and pseudo claw hands were present and the skin was rough and thick with dimpling at the
dorsum of the wrist. Clinically he resembled a Hurler’s phenotype X-rays showed dysostosis multiplex
[broad horizontal ribs, bulleting of phalanges with proximal pointing of metacarpals and broad
ballooned digits, anterior wedging of vertebrae and cloaking of long bones due to periosteal elevation].
Urine examination for mucopolysaccharide was negative. Slit lamp revealed mild corneal clouding.
There was no cherry red spot. The leucocyte mannosidase, fusosidase and betagalactosidase levels were
normal whereas serum arylsuphatase and hexosaminidase levels were elevated confirming the diagnosis
of mucolipidosis type II..He died at 3 year of age with pneumonia and congestive cardiac failure. A
diagnosis of MPS II or Mucolipidosis was reached. Parents were counseled regarding the nature of
disease and prenatal possibilities were explored. Symptomatic treatment was advised.Conclusion
:Mucolipidosis is a close differential of mucopolysaccharidosis but can be clinically and biochemically
differentiated. There is no definitive treatment and symptomatic treatment is advised.
Dipankar Gupta, Megha Consul, Rajesh Mehta
Department of Paediatrics, Safdarjung Hospital and VMMC, New Delhi
Langerhans cell histiocytosis is a rare entity. A five yr old girl presented to the medical facility with
complaints of polyuria, polydipsia and multiple depressed lesions on the skull noticed 3 months back.
No history of trauma, drug intake, radiation exposure or any other significant illness in past was present.
General physical examination revealed Rt. Sided exophthalmos with normal ocular function and
movement, depigmented macular lesions on forehead were seen. Skull had multiple depressed bony
lesions with irregular margins. Systemic examination was unremarkable except for mild hepatomegaly.
On investigations all routine hematologic work up was within normal limits. X-ray skull showed
multiple lytic lesions in both frontal and parietal areas.3D CT Skull showed irregular bony defect in
both frontal, parietal and Rt ethmoidal region. Bone scan was consistent with increased tracer uptake
from above areas only. Water Deprivation test was consistent with Central Diabetes Insipidus. MRI
Brain showed absence of posterior pituitary bright spot and thickening of infundibulum at its origin
(6x7x4.4mm) near the median eminence. Bone Biopsy showed features of Langerhan’s Cell
Histiocytosis consistent with Hand Schuller Christian Disease variety. With the triad of exophthalmos,
diabetes insipidus and lytic skull lesions and supportive imaging and histopathological findings a
diagnosis of Hand Schuller Christian Disease was made.
Sunita Bijarnia, Ratna D. Puri, Seema Thakur, Meena Lall, Renu Saxena, I. C. Verma
Department of Genetic Medicine, Sir Ganga Ram Hospital, New Delhi.
Introduction: Multiple malformation syndrome constitute about 0.7% of all births. These are a
heterogeneous group of disorders presenting a diagnostic challenge. They follow all patterns of
inheritance - sporadic, autosomal and X-linked. Aim: To study the spectrum of children with
dysmorphic syndromes in a genetic clinic. Material and Methods: Cases with dysmorphic features /
multiple malformations referred to the Genetic Clinic at Sir Ganga Ram Hospital over a period of one
year, were included in the study. Careful evaluation of the dysmorphic features and other associated
malformations was performed, followed by search of literature using specialized databases to reach a
specific syndrome. Radiological investigations were performed in some cases. Genetic testing in the
form of karyotyping, FISH studies and molecular testing for mutations in the concerned genes was
performed wherever indicated. Diagnosis of other syndromes was based purely on clinical features and
comparison with similar cases in the published literature. Down syndrome cases were excluded.
Results: Twenty different syndromes were diagnosed. They included chromosomal disorders in 6 Trisomies 13 & 18 and Translocations (2 each), Microdeletion syndromes in 4 cases (Williams, VeloCardio-Facial syndrome, Angelman and Prader-Willi syndrome), and single gene disorders in 3 cases
(Apert syndrome, CDG and Rhizomelic chondrodysplasia punctata). Nine cases were diagnosed on
clinical features and use of dysmorphology databases (Freeman Sheldon, Nijmegen - Breakage,
Kabuki, Johanson Blizzard, Blepharophimosis, Seckel, Smith Magenis, Valproate embryopathy and
Simpson Golabi Behmel syndrome). Conclusions: A specific syndromic diagnosis is essential for an
accurate genetic counseling, prognosis, management and providing the risk of recurrence in subsequent
pregnancies for the families.
Sunita Bijarnia, Ratna D. Puri, Monika Jain, Neelam Kler, Subimal Roy, Andoni Urtizberea, I. C.
Department of Genetic Medicine, Sir Ganga Ram Hospital, New Delhi
Congenital Myopathies are a group of genetic disorders characterized by generalised muscle hypotonia
and weakness of varying severity. They are distinct entities and do not include muscular dystrophies,
metabolic myopathies and mitochondrial disorders. Myotubular Myopathy is a sub type among this
group of disorders. Clinical differentiation of the various types is difficult and requires muscle biopsy
with histopathological and immunohistochemical studies for specific diagnosis. Gene studies are a
prerequisite for genetic counselling and prenatal diagnosis. We present two cases of Myotubular
Myopathy in two families where the diagnosis was established by histopathology and gene studies in
the MTM1 gene. In the first family, the couple was non-consanguineous and the first boy presented at
birth with severe hypotonia and respiratory insufficiency requiring ventilatory management. He died in
neonatal period. Molecular mutation analysis of the MTM1 gene confirmed the diagnosis. The couple
subsequently has one normal girl child. In the second family, also non-consanguineous, there were two
boys affected with congenital hypotonia and weakness and who died in neonatal period. The second
baby was investigated and muscle biopsy with immunohistochemistry was characteristic of Myotubular
Myopathy. The diagnosis was confirmed by molecular analysis, which revealed a c.70C>T mutation in
exon 3 in the MTM1 gene, leading to a stop codon R24X. Genetic counseling was performed regarding
it's X-linked inheritance, their risk of recurrence in 50% in boys in subsequent pregnancies, and a
possibility of prenatal diagnosis.
Renu Saxena, Sudha Kohli, Elizabeth Thomas, I. C. Verma
Department of Genetic Medicine, Sir Ganga Ram Hospital, New Delhi-110 060.
Introduction: Van der Knaap disease or Megalencephalic Leukoencephalopathy with Subcortical Cysts
(MLC) is an autosomal recessive genetic disorder with onset of macrocephaly before one year of age
usually with progressive deterioration of motor functions. This disorder occurs due to mutations in the
MLC1 gene which codes for a putative membrane protein. Aim: To characterize the mutations present
in the Indian MLC1 patients. The common mutation 135insC (c46fs), which has been reported to be
present in Indian patients belonging to the Agarwal community, was looked for by molecular methods.
Materials and Methods: We have analyzed 27 individuals belonging to 22 families. Eighteen patients
were found to be homozygous for 135insC which confirmed the diagnosis of MLC1 in these patients.
They all belonged to the Agarwal community. None of the patients was found to be heterozygous. This
indicates that this common mutation is due to a founder effect and the chance of any other novel
mutation in this community is low. Mutation in four non-Agarwal families were unidentified indicating
that the mutations could be different or some other genes could be involved. Prenatal diagnosis was
offered to 4 families based on molecular methods, and thus enabling them to have healthy children.
Conclusions: The molecular characterization of mutations in MLC 1 patients helps in confirmation of
diagnosis, the carrier screening and prenatal diagnosis of high risk families for the prevention of the
disease. Search is on to devise some therapy based on the pathogenesis of this gene.
Ratna D. Puri, Sunita Bijarnia, Renu Saxena, I. C. Verma
Department of Genetic Medicine, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110060.
Introduction: Skeletal dysplasias are a heterogeneous group of genetic disorders characterized by the
presence of generalized disordered bone growth and/or modeling. Aims and Objectives: To evaluate
patients suspected to have a skeletal dysplasia and study the spectrum of this heterogeneous group of
disorders at a referral centre. Materials and Methods: Patients with disproportionate short stature
referred to the Genetic Department of Sir Ganga Ram Hospital were evaluated by a detailed history,
clinical examination, radiological and biochemical evaluation. Molecular studies were done where
possible. Results: Twenty-six patients with skeletal dysplasias were diagnosed over a three year period.
Five were infants and 21 presented after one year of age. Eight patients were diagnosed to have
Achondroplasia by clinical, radiological and FGFR3 gene mutation analysis. Four patients were
diagnosed to have Osteogenesis Imperfecta, two hypochondroplasia and one Diastrophic dysplasia.
There was one patient each with Asphyxiating thoracic dystrophy, Beals syndrome, Metaphyseal
dysplasia, Spondyloepiphyseal dysplasia and Multiple epiphyseal dysplasia. One infant had Jarcho
Levin syndrome. The diagnosis of Rhizomelic Chondrodysplsia Punctata was confirmed in one
newborn by radiological, biochemical and molecular studies of PEX7 gene. Familial Campomelic
dysplasia was confirmed in one family by mutation analysis of the SOX9 gene. Conclusions: Accurate
diagnosis is important for management and genetic counseling of skeletal dysplasias. These disorders
are not uncommon in India. A good history, clinical and radiological examination is the cornerstone to
the diagnosis of skeletal dysplasais. Molecular studies are a prerequisite for genetic counseling and
prenatal diagnosis.
Ratna D Puri, Sunita Bijarnia, Jyotsna Verma, I. C. Verma
Department of Genetic Medicine, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110060.
Introduction - Glycogen Storage Disorders (GSD) are a group of inherited disorders of glycogen
metabolism characterized by the presence of abnormal glycogen, qualitative or quantitative. There are
many types of GSD and correct diagnosis is essential for appropriate diagnosis, treatment and
counseling of families. Materials and methods: Patients referred with suspected Glycogen Storage
Disorders tothe Genetic Department of Sir Ganga Ram Hospital were evaluated by a detailed history,
clinical examination, biochemical investigations including glucose and glycogen tolerance tests, RBC
glycogen content, enzyme estimation and histopathology on liver biopsy. Molecular tests were done
where possible. These patients were managed by dietary therapy and followed up over the study period.
Results: Glucose tolerance test with estimation of glucose and lactate levels contributed to the diagnosis
of the GSD affecting the liver. Enzyme estimation was done for GSD type II and IX. Of the patients
evaluated, fifteen were confirmed to have GSD. Of these two were diagnosed to have GSD type I, five
GSD type II, six GSD type III, one GSD type V and one patient GSD type IX. Molecular diagnosis was
performed in one patient of GSD type I and GSD IX each. Conclusions: Glycogen storage disorders are
not uncommon in India. It is possible to diagnose the different types of GSD by utilizing commonly
available biochemical tests and further confirmation by molecular analysis thereby allowing
management of the patients by dietary manipulation.