CHAPTER IV
GENETIC DISORDERS CHAPTER IV
GENETIC DISORDER
Following are the diseases which have been found in the present investigation. Their pattern of inheritance
(Fig. 1) extent of burden and descriptions are dealt with in this chapter.
Table 46
Frequency and Pattern of Inheritance of
different genetic disorders
I. SINGLE GENE DISORDERS
(A) Autosomal Dominants
1. Talipes Equinovarus 5
2. Talipes equinovarus 1
flat Rocker bottoro foot
and third toe syndactyly.
3. Talipes Equinovarus bilateral 1
4. Bilateral congenital Talipes 1
Equinovarus with syndactyly
5. A^.'fJi ts Syndrome 3
6. Ectodermal dysplasia 1
7. Marfan's syndrome 1
8. Waardenberg syndrome with hypoplastic 1
cardial and ulner nerves
9. MPS with hypoachondroplasia 1 Contd..,
110 10. Hypoachondroplasia
11. Achondroplasia
12. Achondroplasia with MR
13. Amniotic Constriction band
14. Polydactyly
15. Osteogenesis imperfecta
16. Nail Patella Syndrome
17. Limb reduction
18.. Williams disease
19. Hypoplasia of left hand
20. Noonan Syndrome
21. Facial Dysmorphism
22. Arthrogryposis multiplex
Congentia
23. Ectopia Lentis
24. Tuberous Sclerosis
25. Heredomacular generation
affecting eyes
34
(B) Autosomal Recessive
1 . Thalassemia 11
2 . Mucopolysacchridoses 5
3 . Microcephaly with obscure MR 8
4 . Microcephyaly 20
5 . Microcephaly with MR 3
6 . Delayed milestones with microcephaly 1
and MR Contd
111 7. Microcephaly with delayed milestones
8. Microcephaly with MR
9. Microcephaly with absence of forebrain
10. Microcephaly with MR and polydactyly
13. Microcephaly with short stature
14. Hypocystic Ischaemia Encephalopathy
microcephaly
15. Microcephaly with deafness
16. Anencephaly
18. Congenital cataract
19. Congenital glaucoma
20. Macrocephaly with MR
21. Nightblindness with albinism
22. Congenital deaf and mute with MR
23. Congenital deaf and mute
24. Congenital hypertropic pyloric stenosis
25. Neurocutaneous syndrome (Naxia-
Telangista)
26. F:i’'3le pseudohermaphrodite
27. Congenital adrenal dysplasia
with abnormal genetalia
26. Adrenogenital syndrome
28. Polycystic Kidney
29. Smith-Lemile-oplitz syndrome
30. Lawrence moon-Bardel-Biedl-
syndrome
77 Contd.
112 (C) X-Linked Recessive
1 . Duchenne muscular dystrophy i
2 . Pseudohypertropic muscular dystrophy 2
3 . Hydrocephaly 7
4 . Hydrocephalous with VP shunt block 2
Hydrocephalous with imperforated 1
anus and typical facies
6 . Congenital hydrocephalous due to 1
aqueductus syndrome
7 . Hydrocephalous with no left hand 1
8 . Hydrocephaly with optic atrophy 1
9 . Haemophilia 4
10. Bleeding disorder with mild 1
haemophilia
11. Hunter syndrome 2
12 . Tostj.cular feminization 2
13 . Lesch-Nyhan syndrome 1
26
I I . CHROMOSOMAL DISORDERS
(A) Autosomal
1 . Down syndrome 39
2 . Down syndrome with seperation 1
in palate
3 . Down syndrome with congenital 1
heart disease Contd,
113 4. Down syndrome with HS megaly
5 . Down syndrome with microcephaly
and MR
6 . Tiisomy 18 1
7 . Trisomy 13 1
8 , Trisomy 8 2
9 . Prader w illi syndrome 1
10 , Multiple congenital anomalies 2
11. Delayed development micrognathia 1
cleft, palate, Rolter, facies and
cat cries
(C) Sex chromosomes
1. Abnormal genitalia with incomplete 1
testicular feminization & dehydra-
testosterone deficiency
2. Turner syndrome 3
3. Klinefelter syndrome 2
4. Ambiguous gent'talia with microcephaly 1
5. Ambiguous genitalia 7
6. Ambiguous gen'italia with 1
imperforated anus
7. Micropenis 1
8. Maldeveloped penis 1
68
Contd,
114 III. MULTIFACTORIAL
1. Congenital Aortic Stenosis 1
2. Congenital heart disease with CL & CP 1
3. Congenital cyanotic heart diisease 2
4. Congenital Acyanotic heart disease 3
5. Congenital heart diesese with AV 1
canal defect
6. Congenital heart disease 1
7. Rokitansky-Mayer-Kuster-Hauser 1
syndrome
8. Claw foot and spina bifida 1
9. Spina bifida and hydrocephaly 1
10. Meningomylocoel 1
11. Meningomylocoel with hydrocephaly 1
12. Cl2 ft palate bilateral 1
13. Cleft lip with cleft palate 3
14. Cleft palate 2
15. Mental retardation 31
16. Obscure MR 1
17. Obscure MR with squint 1
18. Obscure MR with dysmorphic features 1
55
IV. PROBABLY GENETIC
1. Primary amenorrhea 3
2. Delayed physical with mental 2
retardation
Contd,
115 3. Delayed milestones
4. MR with physical retardation
and hypotonia
5. Speech defect
6. Dwarfism
7 . Blind with MR
8. MR with hearing asnd visual defect
9. Depressed rudimentary ear with no
cartilage and renal disorder
10. Short stature
11. Male with female features
12. Retarded Growth
13. Delayed milestones with
dv'cmorphism hernia
14. Deformities leg with Inguinal hernia
15. Delayed milestones with obscure
MR and deafness
16. Bilateral undescended testis
17. Minimal Brain Dysfunction Syndrome
28
V. UNCERTAIN
1. Goldenhar Syndrome
2. Hepatosplenomegly (HS megaly)
with MR
3. Ectospadia with Ectopia
vc3ciclG epispermia Contd
116 4. Both Kidneys on right side with l
hydronephrosis
5. Rubinstein Taynbi syndrome i
6. Umbilical hernia 1
7. Cerebral Palsy 1
8. Cornelia de lange Syndrome 2
9. Congenital hypothyroidism 1
12
The above Table lists down the type of disorders that were available in the present investigation.
Microcephaly followed by thalassemia and hydrocephaly were the most common single gene disorders. Most frequent chromosomal disorders were Downs Syndrome and cases of ambiguous genitalia. Among the disorders under multifactorial category cases of mental retardation were higher. Delayed milestones were more in number in the category of probable genetic.
The accompanying Table shows an estimate of the years of impairment and the degree of impairment.
Degree of impairment is difficult to define. According to Carter (1982) it may involve a life long constant handicap as with congenital blindness or a progressive deterioration as with Hundington's chorea which begins with only a minor handicap but ends as total disability. Carter's rough guide to handicap has been
limitation of working capacity in adulthood or in
117 childhood educability. While determining the degree of
impairment in the present investigation nature of
disease, year of detection, possible treatment, kind of handicap and longevity (60 years in India) are taken
into account.
The burden of various genetic disorders in terms of its degree of disability or impairment and the number of years of life lost as a result of the disorder are given in the Table. It can be seen that most of the autosomal dominant disorders do not have any effect on the lifespan and have marginal d isa bility , except the disorder?, like Marfan's Syndrome, Achondroplasia with mental retardation, Nail-Patella Syndrome and tuberous
sclerosis. But the recessive disorders involve greater disability and drastically reduce longevity.
Conditions like anenceph^y, microcephaly with absence of
forebrain are fatal, whereas those like thalassemia, mucopolysacchridoses, polycystic kidney and neurocutaneous syndrome reduce the life span by as many as 55 years. These also involve a greater degree of disability. Same is true for X-linked recessive
disorders where conditions like Hunter Syndrome and
Lesch-Nyhan Syndrome impose the greatest burden both in
terms of reducing longevity and the degree of impairment.
All other X-linked disorders also have reduced life
spans and increased disability. As regards the
autosomal chromosome disorders most of them are fatal
118 and do not warrant survival. They impose the highest
degree of disability and reduction in the life span e.g.
multiple congenital anomalies and the trisomies 18 and
13. While those involving a^berrations of sex
chromosome are comparatively milder in their effect on
disability and longevity. Multifactorial disorders can
be placed fourth in the order of the extent of burden where the neural tube defects,congenital heart disease
and mental retardation contribute major share of the
burden. Most of the disorders placed in probably genetic
category do not have reduced life span but have variable
disability. Among the uncertain category the disability
and life lost is comparatively greater in Rubinstein
Taynbi Syndrome, Cornelia de lange Syndrome and
Congenital hypothyroidism.
119 Table 47
Table showing the estimated burden of the various genetic disorders
S.No. Condition Unimpai red Impai red Degree Lost Cause of life I ife of I i f e death impai re- ment percent
AUTOSOMAL DOMINANT
1. Talipes Equinovarus 60 20 None (untreated)
2. Talipes Equinovarus, 60 25 None Rocker bottom foot and third toe Syndactyly
3. Talipes equinovarus 60 25 None bilateral with Syndactyly
4. Aperts Syndrome Unknown 40 Unknown
5. Ectodermal dysplasia 60 10 0 None
6. Marfan's Syndrome 20 40 15 Aortic complica tion
7. Waardenberg Syndrome 58 30 0 None
8 . Hypoachondroplasia 54 20 0 None
9. Achondroplasia 60 30 0 None
10. Achondroplasia with MR 40 60 20 If heterozygous without complica tions.
11. Afrniotic Constriction 60 10 0 None band Contd.
120 12. Polydactyly (untreated) 0 60 0 0 None
13. Osteogenesis Imperfecta 2 53 40 5 Infection
14. Nail Patella Syndrome 0 20 50 40 Rena I fa ilure
15. Limb reduction (upper limb) 0 60 40 0 None
16. Willi ams Disease 4 Unknown 50 Unknown
17. Hypoplasia of left hand 0 60 40 0 None
18. Noonan SymdruT.: 0 60 40 0 None
19. Facial dysmorphism 10 50 20 Unknown
20. Arthrogryposis Multiplex 0 55 20 After aggressive congent i a physical therapy and orthopedic procedures
21 . Ectopia lent is 60 20 None
22. Tuberous sclerosis 40 80 20 Dementia and i nfect i on
23. Heredomacular degenera- 15 60 40 0 None t i on affect i ng eyes
AUTOSOMAL RfcCESS'VE
1. Thalassemia (without 20 40 40 Increased chelation therapy) i ron burden
2. Mucopolysacchridoses 10 80 50 Pneumonia or cardiac decompo sition
3. Microcephaly wi th 55 90 5 Retardation and obscure MR infection
4. Microcephaly 55 50 5 -do-
5. Microcephaly with MR 45 90 5 - do Contd...,
121 6, MlcrocephaIy with ^5 30 5 - do- delayed milestones
7. Microcephaly with 100 60 Fatal absence of forebrain
8. Microcephaly with 55 80 Retardation and MR and polydactyly i nfect i on
9. Mi crocephaly wi th 55 80 5 - do - short stature
10. Microcephaly with 55 90 5 -do- deafness
11. Anencephaly 100 60 Fatal
12. Congenital wilu.dct 60 20 0 None (Untreated)
13. Congenital glaucoma 59 50 0 None (Untreated)
14. Nightblindness and 60 10 0 None a Ibi ni sm
15. Congenital deaf and 55 60 5 Associated mute with MR retardat i on
16. Congenital deaf and 59 30 0 None mut e
17. Neurocutaneous Syndrome 4 15 95 45 DebiIi ty and infection and maIi gnancy
18. Adrenogenital Syndrome 0 60 30 10 Electrolyte I OSS
19. Polycystic kidneys 30 10 50 30 Renal failure
20. Smith LemiIe oplitz 0 5 60 55 Bronchopneumonia Symdrome
21. Lawrence-Moon-Bardel 40 80 10 Li fespan varies Bieldl Syndrome between 10-60 years
Contd.
122 X-LINKED RECESSIVE
1. Duchenne Muscular 16 60 40 DebiIi ty and dyst rophy i ntercurrent i nfect i on
2. Pseudohypertropic 5 15 60 40 -do- Muscular dystrophy
3. Hydrocephaly (treated) 1 49 20 10 Compli cat i ons
4. HydrocephaIous due to 1 49 20 10 -do- aqueductus Syndrome
5. Hydrocephaly with no 1 49 40 10 -do- left hand
6. Haemophilia 0 50 20 10 Haemorrhage
7. Mi Id haemophiIia 0 55 20 5 -do-
8. Hunter Syndrome 0 20 80 40 Cardiac decompensat i on, pulmonary i nfect i on or neurologic compli cat i ons
9. Testicular f erni ni zat i on 15 45 30 0 None
10. Lesch Nyhan Syndrome 18 80 40 DebiIi ty and mentaI retardat i on
1 . CHHROMOSOMAL DISORDER
AUTOSOMAL
1. Down Syndrome 35 95 25 Associated mal formations or infections.
2. Down Syndrome with 35 95 25 - do- separation of palate (t reated)
3. Down Syndrome with 35 95 25 - do - microcephaly
Contd.
123 4. Down Symdrome with 30 95 25 -do congeni ta I heart di sease
5. T r i somy 18 1 100 59 - do-
6. T r i somy 13 3 100 57 -do-
7. T r1 somy 8 40 80 Un- -do- known
!. Prader Wi U i- 40 90 20 Incurrent Syndrome 1nfect i on due to compli cat i ng obes i ty
9. Delayed development 90 5 5 Associated mal- micrognathia, cleft format i on palate , Rother facies and cat cries
10. Multiple congenital 100 59 - do - anomaIi es
SEX CHROMOSOMAL
1. Abnormal genitalia 15 45 30 None with i ncompIete testicular feminiza tion, dehydratesto- sterone deficiency
2. Turner Syndrome 15 25 30 20 Rena IanamoIi es hypertensi on gonodal tumers
3. Klinefelter Symdrome 15 45 40 None
4. Ambiguous genitalia 0 60 30 None
5. Ambiguous genitalia 0 40 60 20 Mental retarda with mi c rocepha I y tion and i nfect i on
6. Ambiguous genitalia 60 30 Unknown with imperfected anus (treated) Contd. .
124 7. Ambiguous genitalia 60 30 Unknown with micropenis
8. Ambiguous genjtalia 60 30 Unknown with maldeveloped penis
9. Ambiguous genitalia 60 30 Unknown with ectospadias with ectopia vesicle and epispermia
MULTIFACTORIAL
1. Congeni tal Aortic 59 20 None Stenos i s
2. Congenital heart disease 1 59 40 None with CL & CP
3. Congenital Cyanotic 1 30 30 30 Compli cat i on heart disease
4. Congenital acyanotic 40 20 20 F requent heart diseases with Shunt i nfect i on i n VSD fai I i. e yi th hepatosplenomegaly (HS megely)
5. Congenital acyanotic 40 10 20 -do- heart disease (treated)
6. Congenital heart disease 1 59 20 0 None with AV canal defect
7. R ole i tansky-Mayer - Kus t er 18 42 20 None Hauser Syndrome
8. Clawfoot and Spina bifida 0 10 50 50 Infec t i on
9. Spina bifida and hydro- 0 10 50 50 -do- cephaly
10. Meningomylocoel with 0 10 50 50 -do hydrocephaIous
11. MenjngomyIocoeI (treated) 0 10 50 50 • do-
12. Cleft lipwith Cleft 0 60 30 0 None palate (Untreated)
Contd.
125 13. Cleft palate (treated) 0 60 30 0 None
14 Hental retardation 0 40 95 20 Infection
15. Obscure MR 0 40 80 20 -do-
16. Obscure MR with squint 3 57 80 Unknown
17. Obscure MR wi th 0 20 90 40 Infection dysmorphic features
18. Congenital hypertropic 0 60 10 0 None pyloric stenosis (treated)
PROBABLY GENETIC
1. Primary amenorrhea 15 45 30 None
2. Delayed physical and 2 60 50 Unknown menta I mi Iestones
3. Delayed ir, i I es r ?:ies 2 60 30 Unknown
4. MR with physicalretarda- 1 40 95 20 Infection tion and hypotonia
5. Speech defect (untreated) 3 57 40 None
6. Dwa r f i sm 0 60 20 Nene
7. B I i nd wi th MR 1 40 95 20 Infection
8. MR with hearing and 1 40 95 20 -do- visual defect
9. Depressed rudimentary 0 60 20 None ear with no Cartilage and renal disorders
10. Short stature 0 60 20 0 None
11. Retarded growth 0 60 20 0 None
12. Delayed milestones with 1 60 40 Unknown dysmorphism hernia
13. Deformities of leg with 1 60 40 0 None Inguinal hernia
14. Minimal Brain Dysfunction 1 59 20 0 None Syndrome Contd.,
126 UNCERTAIN
1. Goldenher Syndrome 60 AO None
2. Hepatosplenomegly 40 95 20 Infection with MR
3. Both kidneys on the left 60 10 None side with hydronephnosis
4. Rubinstein Taynbi Syndrome 1 14 95 45 Respi ratory tract i nfect i on
5 . CorneIi a de Iange 20 80 40 Infection ■syndrome
6. Congenital hypothyroidism 2 40 95 Unknown
127 The Table below gives the burden of various
genetic disorders encountered in the present
investigation. It has been put into three categories;
high, intermediate and low. This categorization of the
burden is based on the degree of impairment and the life
lost in years as already shown in Table.
Table 48
EXTENT OF BURDEN OF GENETIC DISORDERS
High Intermediate Low
Autosomal Dominant
Achondroplasia with MR, Marfans Syndrome,Waarden Talipes equinovarus
Nail Petella Syndrome. berg syndrome, osteogenesis unilateral or bilateral
imperfecta. Limb reduction, and with syndactyly,
Williams diseases. Hypoplasia Ectodermal dysplasia
of left har>d, Noonan Syndrome, Hypoachodroplsi a,
Facial dysmorphism. Arthro Achodroplasi a,
gryposis multiple congentia, Amniotic constriction
Heredomacular degeneration band, polydactyly, Ectopia
affecting eyes. Lent is.
Autosomal Recessive
Thalassemia, Congenital Glaucoma, Congenital cataract,
Hucopcilysacchridoses, Congenital deaf and albinism with nightblindness.
Microcephaly with MR or mute. Adrenogenital
128 delayed milestones or the syndrome, polycystic absence of forebrain or kidney. short stature or deafness, or HR and
Polydactyly. Anencephaly, congenital deaf and mute with HR, Neurocutaneous syndrome, Smith Lemile-
OpUtz syndrome, Lawrence moon Bardel-Biedl syndrome.
X-Linked Recessive
Ducchenrie muscular Hydrocephaly, Haemophilia, dystrophy, Pseudo Testicular Feminization hypertropic muscular dystrophy. Hunter syndrome,
Lesch Nyhan syndrcxne.
Chromosomal
(a) Autosomal
Down Syndrome, Trisomy 18,
Trisomy 13, Trisomy 8,
Prader will SyrxJronie,
Delayed development with micrognathia, cleft palate
Rother facies and cat cries, Multiple
Congenital anomalies.
129 (b) Sex
AbnormaI Gen«taIi a with
incomplete testicular feminiza
tion, and dehydratestosterone
deficiency, Turner Syndrome,
Klinefelter Syndrome, Ambiguous
genitalia with microcephaI Iy
or imperforated anus,
micropenis, underdeveloped
penis.
Mult i factorial
Congenital cyanotic heart Congenital acyanotic Roki tansky-Mayur-Kuster disease, clau foot with heart disease, congenital Hauser syndrome, cleft spina bifida, spina bifida aortic stenosis, congenital palate, cleft lip with with hydrocephaly heart disease with CL & CP, cleft palate. meningomylocoel, M»?ntal congenital heart disease retardation, obscure HR, with AV canal defect.
Obscure MR with squint, obscure MR with dysmorphic features.
Probably Genetic
Delayed physical and Delayed milestones, speech Dwarfism, short stature, mental retardation, MR defect, depressed rudimentary retarded growth. with physical retarda ear with no cartilage ana tion and hypotonia, blind renal disorder, delayed mile with MR, MR with hearing stones with inguinal hernia. ana visual defect.
130 Uncerta i n
Congenital hypothyroidism, Goldenher syndrome. hepatosplenomegaly with
MR, Rubinstein Taynbi
Syndrome, Cornelia delange syndrome
It can be inferred from the Table 48 that most of
the autosomal dominant disorders fall between
intermediate and low burdens, whereas a greater number
of autosomal and X-linked recessives impose a high
burden. All autosomal chromosome disorders impose high
burden and sex chromosomal disorders are intermediate.
Most of the multifactorial and probably genetic
disorder c: are distributed between high, intermediate
and low burdens. Even those under the uncertain category
also impose high burden.
The description of diseases are based on Birth
Defects Encyclopedia (1990), Nelson text book of
Pediatrics (1990) and Essential medical genetics
(1984) .
131 I. SINGLE GENE DEFECTS
(A) AUTOSOMAL DOMINANT DEFECTS
(1) Achondroplasia
Short limbs especially proximally; normal length trunk with lumber lordosis; prominent forehead with depressed nasal bridge. Adult height is 132 cm in males,
123 cm in female; normal IQ and lifespan. It is an autosomal dominant trait with full penetrance and little variation in expressivity. Incidence 1/26,000
livebirths.
(2) Hypoachondroplasia
Mid to moderate short limb dwarfism with a combination of clinical and X-ray features qualitatively similar to achondroplasia, but generally milder in expression. Mean birth length decreased but in sporadic cases the mild to moderate short stature may not be noticed until 4-6 years of age. Normal life span slight mental retardation which is higher than the general population. Autosomal dominant inheritance.
(3) Apert Syndrome
Craniosynostosis of several sutures; bony
132 syndactyly of digits 2- 5.25 percent have cleft palate
and some mental retardation. Autosomal dominant with
low biological fitness. Paternal age effect for new mutations,
(4) Paroneal muscular atrophy
Onset in teens with bilateral foot drop; enlarged
peripheral nerves; inverted champagne bottle legs; pes
cavus; reduced ankle jerks; some sensory loss; especially for vibration. Normal lifespan with mild to moderate disability. Usually autosomal dominant rarely
automsomal recessive or X-linked dominant.
(5) Huntington disease
Huntington's chorea onset usually in fourth decade; psychiatric symptoms; progressive chorea and dementia. CT scan may show caudate atrophy.
Progressive disability, death in 10-12 years from onset.
Autosomal dominant with complete but age dependent penetrance 10 percent by 30 years, 30 percent by 40, 60 percent by 50. Incidence 1/18000 in U.K and
U.S.A,1/33000 in Japan.
(6) Marfan Syndrome
Arachnodactyly, long limbs with reduced upper to
lower 3.-?gment ratio; lax joints; evidence of
complications. Average lifespan 40-50 years. Treatment
133 A child with talipes equinovarus.
With syndactyly. with bfita blockers may retard progressive
aortic dilatation. Autosomal dominant with 15 percent cases of new mutations.
(7) Waardenburg Syndrome
The combination of lateral displacement of inner canthi, white forelocks, heterochromia iridis, and deafness is characteristic, automsomal dominant.
Prenatal diagnosis not possible. Frequency 1/42000.
(8) Talipes equinovarus
Five per 1000 livebirths have Talipes equinovarus and this is severe in 1 /1 0 0 0 .The sex ratio is 2 males to
one female with a sib risk of 1 in 50 for male probands but 1 in 20 for a female proband. For an affected parent of either sex the risk of recurrence is 1 in 33.
Autosomal dominant inheritance.
(9) Limbs
Overall major limbs malformation are found in
2/1000 new borns.
Polydactyly
Extra digit may occur in the thumb (preaxial) or on the little finger (post axial) and may be a chromosoma] disorder, single gene disorders or be of unknown etiology.
134 (10) Amniotic band
The incidence of transverse limb defect is 1 in
5000. Most of them are due to in utero amputations by
strands of amnion produced by premature rupture of the
amnion.
(11) Ectodermal dysplasia
Expression variable. Sparsity of head and body
hair and dystrophy of nails. Sparse thin, fragile hair with reduced tensile strength on the head, eyebrows and
body. Thick nails with subungual infections. Thick
rough skin on palms and soles with brownish
pigmentation. Autosomal dominant inheritance with
complete penetrance.
Ectopia Lentis
Dislocation of lens, if minimal, may require
dilated slit. Lamp biomicroscopy for diagnosis may be
present at birth or occur later. The patient may have
no symptoms or may complain of poor vision and
monocular diplopia. Bilateral dislocations is the rule.
Autosomal dominant inheritance.
(13) Congenital cataract
Opacities in the lens. The clinical picture
varies from visually insignificant opacities to severe
visual impairment. Difference in the morphology
135 (location, shape and density) are more impressive among
than within the families suggesting genetic variability.
Penetrance is usually high. Autosomal dominant.
(14) Nail-Patella Syndrome
Hypoplastic nails and hypoplastic patella,
dysplasia of the nails, absent or hypoplastic patella.
Abnormality of the elbows interfering with supination,
pronation or extension and iliac horns. The nails of
both hands and feet may be affected, most frequently
those of the index and middle fingers and thumb. The patella may be small, tripartite, polygonal, or absent,
lateral dislocation of the pattela occurs. There may be webbing of the elbow, preventing full extension.
Autosomal dominant with variable expressivity.
(15) Williams Syndrome
Typical facies with full lips, broad nasal bridge,
broad nasal lip and anteverted nares, with or without growth and mental deficiency and supra valvular artic or
pulmonary arterial stenosis. Most frequent features
include mild short stature, sometimes low birth weight, mild to moderate mental retardation, short attention
span with distractibi1ity, with severe behavioural problems in l/6th of patients. IQ most commonly 40-70.
Septal defect in about 75 per cent of the patients.
Sporadic in occurrence, though autosomal dominant
136 inheritance suggested.
(16) Facial dysmorphism
A combination of unusual facies anorexia, cochexia, eye and skin defects and musculoskeletal defects. Possibly autosomal dominant inheritance, although X-linked dominan-c inheritance can be ruled out.
(17) Thalassemia
It is a special type of anemia which appears in infancy or childhood. It is accompanied by enlarged spleen and liver, abnormally shaped red blood cells and an excess of leucocytes in the blood. The severe form of this disease results from the homozygosity of a gene for the condition, but a milder form of the disease results when a person is heterozygous. Thus, the inheritance is single gene intermediate in dominance.
(18) Coloboma of Iris
It is a developmental defect that may take the form of a defect in a sector of the iris, a hole in the substance of the iris, or a notch in the pupillary margin. Simple colobmata are frequently transmitted as an autosomal dominant characteristic, and may occur alone or be associated with other anomalies. An iris
Coloboma may be part of an extensive coloboma involving the fundus and optic nerve as a result of malclosure of the embryonic fissure.
137 (19) Hypoplasia of left hand
A short often bowed forearm with radially deviated wrist. Short forearm slightly bowed to radial side. A prominent knob distally represents the end of the ulna.
The hand is radially deviated. The thumb if present is short or defective. 90 percent are sporadic. A portion of the remainder appears to be of autosomal dominant inheritance.
(20) Limb reduction
Deformation of upper limbs
Multiple, extensive, and variable reduction deformities of upper limbs. Unilateral amelia, unilateral amelia with bidactyly; modification of the configuration of the articular elements of shoulder and elbow, bowed humerus, aplasia of radius, absence of some carpel bones, absence of first radial ray and manus vara. Hypoplasia of humerus, whose remaining part is disarticulated from the glenoid fossa, aplasia of the radius, bowed ulna, absence of some carpel bones, absence of first and second radial rays and manus vara.
They are generally sporadic and due to unknown etiology.
Minority of them are due either to autosomal dominant or autosomal recessive inheritance.
138 (21) Heredomacular Degeneration affecting eyes
The macular dystrophy is characterized by a distinctive yellow or orange discoid subretinal lesion in the mascula, resembling the intact yellow of a fried egg. Diagnosis is usually made from 5-13 years of age; usually vision is normal at this stage. Because of the special histologic features of the macula, certain pathologic processes affecting the retina produce an ophthalmoscopically visible sign referred to as a cherry red spot. The inheritance is usually autosomal dominant.
(22) Tuberous Sclerosis
While skin patches which may only be apparent under ultra violate light (Wood's lamp) (80 percent by 5 years); facial fibroangiomatous rash (50 percent by 5 years); skin fibromatous plaques; (Shagreen patches); enamel pits; phalangeal cysts; whitish retinal phakomata; intra-cranial calcification or periventricular hamartomas on CT scan, evidence of complications. Epilepsy (90 percent); mental retardation (60 percent); variable life span which depends upon the severity of the retardation. Malignant brain turners occur in 6 percent Autosomal dominant inheritance.
139 B) AUTOSOMAL RECESSIVE
(1) Arthrogryposis Multiplex Congenita
Also known as congenital multiple non-progressive
joint contractures shows marked heterogeneity as it can
result from any process which limits movements at a
joint. Four broad categories are recognised myopathic,
neuropathic, connective tissue disorders and extrinsic
limitation of fetal movement.
(2) Congenital Adrenal Hyperplasia
Neonatal vomiting, shock and death in salt losing
form; virilization of the female with ambiguous genetalia; precocity in the male; with correctable
bichemical abnormalities. Normal life span, health and
fertility if promptly diagnosed with replacement
therapy. Autosomal recessive trait in 25 percent. Non
salt- losing and salt losing varieties 30 percent forms
allelic. Incidence 1/40000 births in USA. Deficiency of
21 hydroxylase is the commonest cause (90 percent) but
other rare enzyme deficiencies are known.
(3) Mucopolysaccharidoses (MPS)
Four main ty p es:-
Type (I) (Hurler syndrome, mucopolysacchariduria, deficiency of Alpha-L iduronidase.
Type (II) (Hunter Syndrome);
140
A child with microcephaly
A child with Hunter Syndrome mucopolysacchariduria; deficiency of sulpho-iduronide suplhatase.
Type (III) Sanfilippo syndrome; muco polysacchariduria; deficiency of heparan sulphate sulphatase.
Type (IV) (Morquio disea se); mucopolysacchariduria; deficiency of fibroblast. 6 sulpho-N-acetylhexos aminido- sulphatatase.
Type I has consistent features which include coarse facies in infancy, corneal clouding, short stature,progressive mental retardation, and death in second decade.
Type II as type 1 but later onset and clear corneae; death in third decade.
Type I I I Progressive MR in early childhood; normal facies, stature and cornea; Death in second decade.
Type IV Short stature with scoliosis; normal intelligence, facies and corneae, atlantoaxial subluxations; death in third decade. Autosomal recessive with exception of type II which is X-linked recessive.
Combined frequency 1/20,000 with type 3 most common.
{1} ''icrocephaly
Microcephaly is an abnormally small head (head circurnference less than 3 SD below the mean) which reflects defective brain growth. Identifiable causes include congenital infection, birth trauma, chromosomal imbalance, maternal phenylketonuria, and several
141 autosomal recessive entities.
The recurrence risk depends upon etiology. If parents are consanguineous,or if two children are affected, autosomal recessive inheritance is likely, for isolated case suggests that recessive inheritance to be a major contributing factor.
(5) Infantile polycystic disease
This is an autosomal recessive trait results in cysts in the liver, kidneys, and pancreas, which interfere with function and so result in death in early childhood.
(6) Congenital deafness
Deafness in sensorineural and essentially symmetric bilaterally, is present at birth or shortly thereafter, and is non-progressive after it becomes manifest. There is severe hearing loss. Defective speech and language development results unless early training is instituted. Emotional problems can occur if the hearing loss is not recognized and child is not treated appropriately. Autosomal recessive with variable penetrance.
(7) Congenital Glaucoma
This relatively rare form of glaucoma is diagnosed
142 within the first year of life in 80 per cent of cases.
Clinical signs include lacrimiation, photophobia, irritability and pain, blepharsospasm corneal clouding, corneal enlargement, horizontal ruptures in Descemet membrane, and cupping and atrophy of the optic discs.
It is bilateral in 50-75 per cent of cases and more common in males. Autosomal recessive in 30 per cent.
Sporadic cases are more common.
(8) Smith-Lemli-Oplitz-Syndrome
One half infants manifest prenatal onset of growth retardation. Characteristic cranio-facial features include microcephaly, narrow high forehead with prominent metopic suture, broad nasal bridge, short nose with anteverted nostrils, bilateral epicanthal folds, ptosis, broad maxillary alveolar ridges, cleft of the posterior palate, micrognathia and abnormally shaped or positioned pinnae. Approximately 70 per cent of 46 XY males with this syndrome have abnormalities of external genetalia. Autosomal recessive inheritance.
(9) Osteogensis Imperfecta
Skeletal fractures with minimal trauma / or evidence of osteopenia and / or blue sclera.
Considerable heterogeneity exists in phenotype and in genetic transmission. It is a term applied to a group of multisystem diseases involving skeletal, ocular, cutaneous, otologic, dental and vascular tissues.
143 Greater morbidity due to skeletal system. The spectrum of severity varies considerably. Patients range from those with severe neonatal onset characterised by multiple intrauterine fractures of the limbs and ribs, soft membranous cranium and usually neonatal death from
intracranial haemorrhage. There are other manifesting only a slight tendency towards or no history at all of bone fractures but with blue sclera or mild deafness.
Etiology genetically and clin ically heterozygous. The vast majority appear to be inherited in an autosomal dominant manner from previous generation or when parents are consanguineous and c lin ically normal autosomal recessive inheritance.
(10) Lawrence-Moon-Bardel-Biedl Syndrome
Hypogenitalism, mental retardation, retinitis pigmentosa, spastic paraplegia. Hypogenitalism present at birth but may not be noticed until later when normal genital growth is not observed. Slow development, night blindness, mental retardation and ataxic gait noticed during childhood. Retinal pigment accumulation noticed peripherally in late childhood and gradually encroach the central retina accompanied by progressive optic atrophy. Presumably autosomal recessive inheritance.
(11) Albinism
Foveal hypoplasia, reduced visual acuity that
144 cannot be corrected to normal, reduced pigment in the retinal pigment epithelium and misrouting of the retinal ganglion fibres at the optic chiasm are cardinal features of all type of albinism. Mild to total reduction of melanin pigment in the skin, hair and iridis are features of oculo-cutaneous albinism.
Minimal to no reduction of melanin pigment in the skin and hair, with varying degree of iris pigment are features of ocular albinism. Albinism is autosomal recessive inheritance except ocular albinism which is
X-linked recessive.
(12) Neurocutaneous syndrome
Ataxia telangiectasia, an autosomal recessive condition, is the most common of the degenerative ataxias and is heralded by ataxia beginning at about 2 years of age. Oculomotor apraxia, defined as having difficulty fixating smoothly on an object and therefore overshooting the target with lateral movement of the head followed by "re -fixating" the eyes, is a frequent finding, as in horizontal nystagmus.
Examination of skin shows a loss of elasticity.
Children with ataxia telangiectasia have a 50 to 100 fold greater chance of developing lymphoreticular tumors
(lymphoma, leukemia, and Hodkins disease) as well as brain tumors compared with the normal population.
Additional laboratory abnormalities include an increased incidence of chromosome breaks, particularly of
145 chromosome 14 and elevated level of fetapro teins.
Death results from infection or tumor dissemination.
(13) Female Pseudohermaphroditism
The most common cause of female pseudohermaphroditism is congenital adrenal hyperplasia.
The incidence is about 1 in 25,000 births. Several distinct genetic and clinical forms are known, all inherited as autosomal recessives and each characterised by a block in a specific step in cortisol biosynthesis resulting in increased secretion of ACTH and hyperplasia of the adrenal glands. This in turn leads to masculinization of female fetuses. Affected baby girls frequently have major anomalies of the external genitalia, often to the point that sex assignment may be impossible. The clitoris may be enlarged and the labia majora rugose end even fused. In males the same genotype produces premature virilization, but there is no difficulty in identifying the sex.
(C) X-LINKED RECESSIVE
(1) Androgen insensitivity syndrome (testicular feminization) syndrome
Female phenotype with normal breast development but primary amenorrhea and paucity of pubic and other body hair; blind vaginal pouch, intra-abdominal testis,
46 XX Karyotype, Ingunial herniae (50 per cent); gonodal
146 neoplasm if not removed (5-20 percent); in fe rtility (100 percent) normal IQ and lifespan. X-linked recessive trait incidence 1/62400.
(2; Kaemophilia
Recurrent haemorrhage post operatively and spontaneously into soft tissues and joints; Factor VIII less than 30 percent of normal. With factor VIII intravenous replacement therapy lifespan near normal. X-
Linked recessive trait. Incidence is 1/5000 male b ir t h s .
(3) Lesch-Nyhan Syndrome
Onset in infancy with progressive spasticity and choreoathetosis; later mental retardation is evident and self mutiation. X-linked recessive.
(4 ) Muscular Dystrophy X-linked
There are two main types -
Duchenne muscular dystrophy (DMD)
Onset in early childhood of progressive proximal muscle weakness, calf pseudohypertrophy; marked elevation of serum creatine kinase; abnormal electromyogram and muscle biopsy, mild mental retardation (25 percent), chairbound about 10 years; death about 20 years.
147 Becker muscular dystrophy(BMD)
Onset of progressive muscular weakness in late
childhood; calf pseudohypertrophy; also abnormal
electromyogram and muscle biopsy. Often chairbound
about 25 years from onset. Lifespan may be normal.
Both inherited as X-linked recessive traits. DMD
incidence 1/3000 male birth and BMD 1/20000 births.
(5) Pseudohypertropic muscular dystrophy
Pelvic weakness and atrophy accompanied by
pseudohypertrophy of the calves and tight heelcords in a male child, manifested between 3-5 years of age; highly
elevated serum creatine kinase. Usually X-linked
recessive inheritance.
(6) Hydrocephaly
Hydrocephalous is an enlarged head due to
interference with the normal circulation of cerebro
spinal fluid. With successful surgical shunting, 80
percent have normal intelligence.
One per 1000 neonates has hydrocephalous which may
be due to a neural tube defect, intracranial
haemorrhage, or fetal infection or be inherited as a multifactorial, X-linked recessive or autosomal
recessive trait.
148 A child with Downs Syndrome
A Child with Pradder W illi Syndrome I I . CHROMOSOMAL DISORDERS
A) AUTOSOMAL CHROMOSOMES
(1) Downs Syndrome
The overall incidence of trisomy 21 is 1 per 700 livebirths. Incidence at conception is, however, much greater but more than 60 percent are spontaneously aborted,and at least 20 percent are still born. The incidence increases with increasing maternal age.
Clinically palpebral fissures are upslanting, with specking of the iris, the nose is small, and the facial profile flat. In the neonate hypotonia may be marked and redundant folds of skin about neck are regular features of this and several other chromosomal disorders. A single simian crease present (50 percent) and little finger short and curved (50 percent).Mental retardation is the most serious complication. The IQ is usually less than 50 and if not mosaicism should be suspected.
Other complications are also present. Most cases are trisomy 21 (95 percent).In 80 percent cases mother contributes the extra chromosome.
(2) Trisomy 18 (Edward syndrome)
The incidence of trisomy 18 is 1/3000 livebirths with rr.auernal age effect. The incidence at conception is much higher, but 95 percent of affected fetuses abort
149 spontaneously. At birth there is preponderance of
females than males. Low birth weight and multiple dysmorphic features are apparent in the newborn. These
include a characteristic skull shape with a small chin and prominent occiput,low set malformed ears,
clenched hands with overlapping index and fifth
fingers,single palmer creases, rockerbottom feet and a short sternum.
Malformations of the heart,kidneys and other organs are frequent, and 30 percent die within a month.
Only 10 percent survive beyond the first year and these
infants show profound developmental delay. Parental non-disjunction at first or second meiotic division
results in the extra copy of chromosome 18.
(3) Trisomy 13
The incidence of trisomy 13 is 1 per 5000
livebirths with a maternal age effect. Multiple dysmorphic features are apparent at birth. These
include hypotelorism reflecting underlying holoprosencephaly, micropthalmia, cleft lip and palate,abnormal ears, scalp defects, redundant skin about the nape, clenched fists,single palmer creases (60 percent), post axial (little finger side) polydactyly, prominent heels and cryptorchidism in the male.
150 Congenital heart disease is usual, and 50 percent die within a month. Only 10 percent survive beyond the first year. Non-disjuction in either parents may cause trisomy 13.
( 4 ) Trisomy 8th
Multiple congenital abnormalities include dysmorphism facies with everted lip, large ears and prominent forehead. Skeletal features include a long, thin, trunk, rib and vertebral anomalies, with multiple joint contractures absent or dysplastic patellae, camptodactyly and chinodactyly.
(5) Prader willi syndrome
In the newborns hypotonia and poor swallowing may be marked. The face is flat with a tented upper lip, and the external genitalia are hypoplastic. In later childhood the hypotonia improves and overeating with obesity occurs. Hands and feet are small. Mental retardation universal.
In about 50 percent there is deletion in the long arm of chromosome 15.
SEX CHROMOiiOME
(1) Klinefelter syndrome
Overall incidence of 47 XXY is 1 per 1000 male with an increased risk at increased maternal age. The
151 frequency is increased in the infertile males (100/1000) and in males in institutions for the mentally retarded
10/1000. The diagnosis generally made during adult life at the investigation of infertility, small testes, inadequate production of testosterone leads to poorly developed secondary sexual characteritics. Elongated limbs and upper to lower segment ratio is abnormally low. Intelligence is 10-15 IQ points below the normal sibs with 20 percent mildly mentally retarded. The extra
X chromosome is of maternal origin in 60 percent and paternal in 40 percent.
(2) Turner syndrome
The overall incidence is 1/5000 females births.
The frequency at conception is much higher but over 99 percent spontaneously abort. In newborn diagnosis may be suggested by redundant neck skin and peripheral lymphoedema. But frequently the diagnosis is made only in the later years,during the investigation of short stature or primary amenorrhea. Proportionate short stature is apparent from early childhood, no adolescent growth spurt occurs, broad chest, with impression of widely spaced nipples,the hair line is low and the neck may be webbed. Congenital heart disease present in 20 percent and there is also an increased risk of unexplained systemic hypertension. Intelligence and life span normal. Monosomy X may arise from non-
152 A Child with Micropenis
A Child with ambiguous genitalia disjunction in ?.il.f-ier parent. In 75 percent with monosomy X ci 1 the maternal X chromosome is present.
(3) Ambiguous Genutalia
In some newborn infants assignment of sex is difficult or impossible because the genitalia are ambiguous, with anomalies that tend to make them resemble those of the opposite sex. The anomalies vary through a spectrum from a mild form of hypospadias in the male to enlarged clitoris in the female, with many intermediate states and many degrees of severity. Such problems do not necessarily involve abnormalities of the sex chromosomes, but may be due to single gene defects or environmental causes.
III. MULTIFACTORIAL DISORDERS
(1) Neural tube defect
Defective closure of neural tube may occur at any level. Failure at cephalic end produces anencephally and failure lower down produces spina bifida. These are equally frequent and co-exist in about 20 percent of cases.
In anencephaly the cranial vault is missing and the exposed nervous tissue degenerates. Still birth or neonate:J death is invariable.
Spina bifida is most commonly lumbosacral with
153 paralysis of the legs and sphincters.About 15-20 percent have a covering of intact skin. Hydrocephalous occurs
in 80 percent.
There appears to be increased frequency in lower
social classes and with winter born children. The
epidemiological evidence and genetic analysis favours multifactorial inheritance with important environmental
components.
(2) Heart defects
Congenital heart lesions affect 8/1000 births, with a risk to sibs or offspring of about 1 in 25.
Recurrence is not specific to the type of heart lesion.
Prognosis varies with the lesion and improvement in the cardiac surgery meant that some previously lethal
lesions are now curable.
(3) Cleft lip and patate (CL & CP)
Cleft palate and/or cleft lip occurs in 1/1000 births and is most often due to m ultifactorial
inheritance, although it may be a feature of over 150 single gene traits (e.g.Treacher Collins syndrome) or chromosomal abnormalities (e.g. Trisomy 13). Surgical repair without sequelae is usual.
For the multifactorial lesions the recurrence risk for normal parents with a child with unilateral cleft
154 A Child with meningomyelocoel lip is 1 in 50 and rises to 1 in 20 if child has bilateral cleft lip. Cleft palate without cleft lip also shows multifactorial inheritance but is distinct from
‘ t .lip and/palate.
C4) Congenital Hypertropic Pyloric stenosis
Pyloric stenosis affects approximately 1 : 150 male and 1 : 750 female infants. It occurs more frequently in the first born male infants. Familial incidence is observed in about 15 percent of parents, but no specific pattern of inheritance has been established. Multifactorial inheritance is likely.
Pyloric stenosis is not present at birth. Initially there is only regurgitation or occasional nonprojectile vomiting. The onset rarely occurs before one week of age, usually in the 2nd, 3rd week; it is seldom delayed until 2nd-3rd month.
(5) Meningomyelocele
Midline spinal defect with neurologic deficit. A visible sac or epithelial defect over the spine, caudal to the level of the lesion in which nerve tissue can be seen and associated with neurologic deficit. The skin lesion differs from one that is almost completely skin covered to a fully exposed lower spinal cord and cauda equina . Hydrocephalus is present in about 20 per cent of patients. Multifactorial inheritance, nutritional factors may play a role.
155 (6) Rokitansky - Mayer Kuster - Hauser syndrome
Congenital absence of uterus in a 46 XY individual with normal ovarian development and normal female external genitalia or Fallopian tube may persist. The individuals show normal sexual development except for the absence of fallopian tubes, uterine corpus. uterine cervix, and the upper portion of the vagina are absent. The external genitalia are those of a normal female. Hymen is intact, but the vagina ends blindly.
At puberty normal secondary sexual development occurs.
The presenting symptoms is most often primary amenorrhea. Multifactorial inheritance is most likely.
(7) Mental Retardation (MR)
3.4 per cent of the population are mentally retarded with an IQ of less than 70. The majority of these individuals 3 per cent have an IQ between 50 and
70 (mild mental retardation) and these individuals show twin concordance and family correlations which support mullfactorial inheritance. Occasionally a single gene
(e.g. neurofibromatosis) or chromosomal (e .g . 47 XXY) disorder is responsible.
Moderate and severe mental retardation (IQ < 50) affects 1 percent of newborns, but this incidence falls to 0.3 - 0.4 percent in older children due to death in
156 infancy. The single commonest cause is trisomy 21. When the chromosomes are normal and no other cause can be
identified then the defect is either autosomal or X-
linked recessive.
IV. PROBABLY GENETIC
(1) Primary Amenorrhea
This indicates that menarche has never occurred.
In primary amenorrhea, chromosomal or congenital abnormalities such as gonodal dysgenesis, the triple X- syndrome, isochromosomal abnormalities, testicular feminisation syndrome, and, rarely, true hermaphroditism, should be considered in addition to the conditions that cause secondary amenorrhea. Both types of amenorrhea may be caused by chronic illness particularly that associated with malnutrition or tissue hypoxia such as diabetes mellitus, inflammatory bowel disease, cystic fibrosis or cyanotic congenital heart d is e a s e .
(2) Minimal Brain Dysfunction Syndrome
The term designates the central disturbances of a group of children hereto labeled as suffering from hyper
activity, hyperkinesis, minimal brain damage or minimal
cerebral dysfunction. Opinion vary as to the origin and
features of this disorder. Some believe it to be
resulting from disturbances in the neurochemistry or
157 neurophysiology of the central nervous system, with metabolites of brain catchoamines receiving particular attention. Recent studies have emphasized a genetic component. The random motor movements and social intrusiveness, may diminish, but learning disabilities and behavioural and psycho-social problems may become even more intense and handicapping in late childhood and adolescence.
V. UNCERTAIN
(1) Goldenher Syndrome
External ear malformations with associated middle ear anomalies and conductive hearing loss, macrostonia, mandibular hypoplasia, epibulber - dermoids or lipo- dermoids, and/or anomalies of cervical spine. Pattern of inheritance consists with autosomal dominant, autosomal recessive and m ultifactorial.
(2) Ectospadias
Exstrophy of the urinary bladder occurs about once in every 10,000-40,000 births. It is more common
in boys than in girls. The severity ranges from a small cutaneous fistula in the abdominal wall or simple ectospadias to complete extrophy of the cloaca involving exposure of the entire hindgut and the bladder. In classic bladder exstrophy the bladder protrudes from the abdominal wall and its mucosa is exposed. The umbilicus
158 is displaced downwards the public rami are widely separated in the midline, and the recti muscles are separated.
(3) Rubinstein Taybi Broad Thumb Hallux Syndrome
The finding of broad terminal phallanges of the thumb and halluces, with or without angulation deformity, characteristic facial appearance with beaked or straight nose, broad nasal bridge, mild retrognathia; stature, head circumference, and bone age below the 50 percentile; mental, motor, language, and social retardation and incomplete or delayed descent of testes constitute the clinical syndrome. Etiology is undetermined.
(4 ) Cornelia de lange Syndrome
Physical and mental retardation, hirsutism and synophrys, microcephaly, long or protruding, philtrum, anteverted nares, small or grossly malformed hands, and webbing of second and third toes, etiology is unknown in majority. Autosomal dominant or autosomal recessive suggested.
(5) Congenital hypothyroidism
Congenital causes of hypothyrioidism may be sporadic or familial, goitrous or non goitrous. In many cases the deficiency of thyroid hormone is severe and
159 symptoms develop in the early weeks of life. In others,
lesser degrees of deficiency occur, and manifestations may be delayed for months or years. The prevalence of congenital hypothyroidism has been found to be 1 in
4,000 infants worldwide, lower in Japan (1 in 5,500) and
in African-Americans (1 in 32,000). Developmental defects account for 90 percent of infants in whom hypothyroidism is detected; in about one third even sensitive radionuclide scans can find no remnants of thyroid tissue. In most of the other infants, rudiments of thyroid tissue are found in an ectopic location anywhere from the base of the tongue (lingual thyroid) to the normal position in the neck. Most infants with congenital hypothyroidism are asymptomatic at birth even when there is complete agenesis of the thyroid gland.
160