9 Year Old Boy Chromosomal Abnormality
Transcript of 9 Year Old Boy Chromosomal Abnormality
9 Year Old Boy with Chromosomal Abnormality
Matthew Wise, MDMed‐Peds
Endo
September 13, 2012
HPI• Birth History: full‐term, uncomplicated, 5lb 15oz
• Neonatal period: mom noticed 5th
digits were bent inward, noticed widened space between his eyes,
and small penis –
pediatrician reassurance
• Developmental Delays:
‐
walked at 17mo
‐
speech delayed until 4 years
• Behavioral concerns‐
sensitive to smells/textures
‐
anxiety, frequently frustrated
Pediatrician Eval
• 8 years, 5 months –
karyotype:
48, XXYY
Subsequent Evaluation
• Connected with developmental pediatrician in Denver, CO with expertise in 48,XXYY
• Spent 1 week receiving further medical/neuropsychiatric evaluation
• Anxiety prescribed citalopram
• Advised to establish care with a peds endocrinologist to discuss pubertal issues
• Online support group
Pubertal and Growth History
Peds
endo
clinic 9yr 6mo
• No body odor• No growth spurt• No acne• No genital growth• Pubic hair noted 1 month prior
PMH and ROSPMH
• 48, XXYY chromosomal disorder
• Developmental delay with speech
delays/learning disabilities
• Anxiety disorder
• Appendectomy age 5
ROS
• Transient improvement in
anxiety, anger outbursts with
citalopram, worsening again
• Chronic constipation
• Chronic dry skin
• Dental problems
MEDICATIONS• citalopram
10mg daily
• hydrocortisone cream prn
Family and Social History
Family
• Mother 39yrs, 5’3”, 125lbs, menarche 13‐14, 1 miscarriage
• Father 41yrs, 5’7”, 185lbs, HTN, dyslipidemia, ?early puberty
• Mid‐parental height = 5’
7.5”
• Brother 12yrs, body odor x1yr, ? If other pubertal changes
• Brother 7yrs, asthma
Social
• Suburban home
• 3rd
grade, public school, with IEP
• Stay at home mother, father in health‐care
• Therapeutic horse back riding
Physical ExamVSS Wt 54.1kg (95%ile), Ht 144.1cm (88%ile), BMI 26.1 (98%ile)Gen: Awake, alert, shy, poor eye contactHead/Face: Mild hypertelorism, epicanthal
folds
Neck: no thyromegaly, no acanthosisResp:
Clear bilaterally, unlabored
CV: RRR no m/r/gAbd: Soft, scaphoid, non‐tender, no massesGU: No palpable breast tissue
Few coarse pubic hairs at base (Tanner III), stretched penis 4.7cmTestes descended, pre‐pubertal 1cm R, 1cm L (volume ~1mL)No axillary
hair
Ext: clinodactyly
of both 5th
digitsNeuro: no focal neurologic signsDerm: no acne
Assessment and Evaluation
48, XXYY male (9y6m) with pubarche‐
LH
‐ FSH
‐ Total testosterone
‐ Free testosterone
‐ DHEA‐SO4
‐ Bone Age
Evaluation and Recommendations
‐ LH <0.1 mIU/mL
‐ FSH 0.6 mIU/mL
‐ Total testosterone 7.1 ng/dL
‐ Free testosterone 0.2 ng/dL
‐ DHEA‐SO4 43 ug/dL
‐ Bone Age 11.4 years (+2.5 SD) 72.4 inches
• Adrenarche, but no true puberty
• Reviewed risk for hypogonadism, future need for testosterone
• F/u in 6 months
Clinical Questions
1) What clinical findings are typical in 48, XXYY?
2) What is known about the natural history of growth/puberty in patients with 48, XXYY?
3) How do clinical findings in 48, XXYY compare to Klinefelter
syndrome?
48, XXYY
• First described 1964• 1:18,000 –
1:40,000 (vs. 1:650 for 47,XXY)
• Initially considered “variant”
of 47, XXY
• Now felt to have unique medical, neurodevelopmental, psychiatric characteristics
48, XXYY Cross‐Sectional Study
• 2008• Multicenter, n=95 (US 66, Canada 5, Europe 23, Aus 1)
• Mean age 14.9 (1.8‐55), 97% Caucasian
Tartaglia et al 2008Mean age at Diagnosis 7.7 yrs
Clinical Features
Clinodactyly 80%
Pes
planus 79%
Hypertelorism 72%
Poor dentition 71%
Pectus
excavatum 62%
Upslanting
palpebral
fissures
58%
Epicanthal
folds 55%
Facial asymmetry 52%
Age <10
Tartaglia et al 2008
Clinical Features
Tartaglia et al 2008
Clinical Features
Tartaglia et al 2008
Associated Conditions• Learning disability (100%)
• Speech delay (92%)
• Dental problems (88%)
• Motor delay (75%)
• ADHD (72%)
• Intention tremor (61‐73%)
• Asthma (60%)
• Food allergies (56%)
• Mood disorders (47%)
• Constipation (40%)
• Gynecomastia
(25‐41%)
• Cardiac (19%, VSD most common)
Tartaglia et al 2008
Associated Conditions• Learning disability (100%)
• Speech delay (92%)
• Dental problems (88%)
• Motor delay (75%)
• ADHD (72%)
• Intention tremor (61‐73%)
• Asthma (60%)
• Food allergies (56%)
• Mood disorders (47%)
• Constipation (40%)
• Gynecomastia
(25‐41%)
• Cardiac (19%, VSD most common)
Age 11‐19 Prevalence
DM2 0%
Hypothyroidism 10.5%
Obesity 9.7%
Age >20 Prevalence
DM2 18.2%
Hypothyroidism 9.1%
Obesity 31.8%
Tartaglia et al 2008
Puberty in 48, XXYY patients
• Additional X in males leads to testicular dysgenesis
and hypergonadotropic
hypogonadism
• All pts >20 yrs (n=22) had microorchidism, elevated LH with low/low‐nml
Test
• Avg
age for initiation: 14.9yrs (11‐31)
• Only 64% of pts in adult group were actively on testosterone
3 – previously treated, lost to f/u
3 – concern regarding worsening behavioral sx
1 –
disliked the effects
1 – had elevated LH but low‐nml
testosterone, not rx’d
Tartaglia et al 2008
Stature in 48, XXYY Patients
• Mean adult stature 6ft 3.7in (SD 3 inches)
‐
More variable in childhood
‐
Tall stature may be related to over‐expressed SHOX
‐
? another growth control gene on Y chromosome
Tartaglia et al 2008
Klinefelter
Syndrome vs
48, XXYY47, XXY 48, XXYY
Prevalence 1:650‐1000 1:18,000‐40,000
Age of Dx 3.6% before age 10 70% before age 10
Parent of origin 50% maternal50% paternal
100% paternal
Stature 188 cm = 6 ft 2 inches 192.4 cm = 6 ft 3 inches
CongenitalMalformations
Clindodactyly
common
Other 18%
Clinodactyly
commonOther 56%
HypergonadotropicHypogonadism
Yes Yes
DevelopmentCognitive
Speech/Motor 40‐75%Learning disability 50‐75%FS‐IQ 89‐102Verbal IQ > Performance IQ
Speech/Motor 72‐92%Learning Disability 100%FS‐IQ 70‐80Verbal IQ > Performance IQ
Tartaglia et al 2008
Take Home
• 48, XXYY is a rare cause of hypergonadotropic hypogonadism
in boys
• Compared to 47 XXY, males with 48 XXYY have greater severity/frequency of neurodevelopmental
disorders
(including language‐based cognitive deficits and problems with adaptive functioning), dysmorphic features, and medical comorbidities, and tend to be
taller
• Testosterone replacement is indicated in 48 XXYY patients, and rarely may be associated with worsening
behavioral symptoms
References
Tartaglia
et al. 48, XXYY, 48, XXXY, 49, XXXXY syndromes: not just variants of
Klinefelter
syndrome. Acta
Paediatrica
2011; 100:851‐860.
Tartaglia
et al. A new look at XXYY syndrome: medical and psychological features. Am
J Med Genetics 2008; 146A(12): 1509‐1522.
xxyysyndrome.org
xxyysyndrome.org