This patient presented with congenital hypoparathyroidism and seizures at 2 months of age. He had severe growth retardation and characteristic facial dysmorphisms including prominent forehead, deep set eyes, microcephaly, thin upper lip, beaked nose, and small hands and feet. Based on these findings he was diagnosed with Sanjad-Sakati Syndrome, a rare autosomal recessive condition characterized by hypoparathyroidism, severe growth issues, intellectual disability, and specific facial features.

1. Spot diagnosis
DR. CRYSTAL SHARON DANTHI

2. Case 1:
 A 20-month-old boy with weight of 1.9 kg (<3% percentile) and length of 45 cm (< 3% percentile) was
brought to pediatric ER with dyspnea, tachypnea, and hypoxemia.
 He had multiple congenital anomalies including cleft palate, congenital bone defects (radial ray anomalies
including right absent thumb and left partially formed thumb without bone formation, syndactyly in the left
foot, thin extremities, bilaterally pes equinovarus, short stature, saddle nose, and frontal bossing), low-set
ears, micrognathia, truncal hypotonia, macrocephalus with hydrocephalus, hypotrichosis including scarce
eyelashes, eyebrows, and hairs, hypodontia, erythematous skin changes and telangiectasias on extremities,
thin and dry skin, micropenis and small testes.
 He had hyponatremia (110 mEq/L), hypochloremia (79 mEq/L), hypocalcemia (total 7.2 mg/dL,
ionised calcium 3.8 mg/dL), hypokalemia (3.5 mEq/L), elevated transaminases (AST 152 U/L, ALT 54
U/L), high CRP (16.2 mg/L) and high creatinine (0.54 mg/dL); Venous blood gas was normal.

3.  He was second born out of a consanguineous marriage (second degree cousins), born by
emergency CS at 35 weeks of gestation. Birth weight was 1300 gram.
 His sister who was 4.5 years old had the same congenital bone defects plus dermal
findings including hyperpigmentation and multiple telangiectasias on her face and
extremities
 He was operated for anal atresia at 13 day of life. He had recurrent vomiting and
diarrhea without a specific diagnosis to date.

4. Figure 1a.
Hypotrichosis, saddle nose,
low-set ears, micrognathia,
absent right thumb,
syndactyly, erythematous skin
changes, atrophy and
telangiectasias.
Figure 1b.
Radiological findings showing
absence of epiphyses,
malformed radius, short
metacarpal and phalangeal
bones, and absence of first
metacarpus and phalanx.

5. Rothmund–Thomson syndrome {RTS} or
poikiloderma congenitale
 Rare congenital autosomal recessive disorder ;attributed to mutations of the RECQL4 helicase gene
on 8q24.
 Poikilodermatous skin changes and photosensitivity, skeletal, dental and nail abnormalities, juvenile
cataracts, sparse hair, eyelashes, and, or eyebrows, small stature and predisposition to skin cancer
and osteosarcoma are some key features of this syndrome.
 Described in all races and many nationalities and no clear gender predilection.
 The most consistent feature of the syndrome is skin findings. The cheeks are usually first involved
with red patches or edematous plaques, sometimes with blistering. Over months to years, the rash
enters a chronic stage characterized by atrophy, telangiectasias, pigmentary changes {poikiloderma}
and spread to other areas of the face, the extremities, and the buttocks.

6. HEAD & NECK
Face
- Frontal bossing
- Prognathism
Eyes
- Juvenile zonular cataracts
- Microphthalmia
- Microcornea
- Strabismus
- Glaucoma
- Mesodermal iris dysgenesis (in some patients)
Nose
- Small, saddle nose
Teeth
- Microdontia
- Delayed eruption
- Supernumerary teeth
- Missing teeth
- Multiple crown malformations
ABDOMEN
Pancreas
- Annular pancreas
Gastrointestinal
- Anteriorly placed anus
GENITOURINARY
Internal Genitalia (Male)
- Cryptorchidism
SKELETAL
- Osteoporosis
Spine
- Kyphoscoliosis (in some patients)
Pelvis
- Congenital hip dislocation (rare)
Limbs
- Forearm reduction defects
- Absence of patella
- Hypermobile joints (rare)
- Restricted range of movement in some joints (rare)
Hands
- Hypoplastic thumbs
- Small hands
Feet
- Small feet
- Club feet
SKIN, NAILS, & HAIR
Skin
- Erythematous skin lesions in infancy
- Poikiloderma (atrophic plaques with telangiectasia)
- Telangiectasia
- Skin atrophy
- Sun sensitivity
- Shallow indolent cutaneous ulcers (in some patients)
Nails
- Atrophic nails
Hair
- Sparse hair
- Alopecia
- Premature graying of hair
ClinicalFeatures

7. NEUROLOGIC
Central Nervous System
- Mental retardation in 5-13%
ENDOCRINE FEATURES
- Hypogonadism
NEOPLASIA
- Basal cell carcinoma
- Squamous cell carcinoma
- Osteogenic sarcoma
MOLECULAR BASIS
- Caused by mutation in the Req-
like DNA helicase type 4 gene
(RECQL4, 603780.0001)
INHERITANCE
- Autosomal recessive
GROWTH
Height
- Short stature

8. Case 2
 An 8 year old female born of non-consanguineous marriage presented with weakness of left
side upper and lower limb, generalized headache, bodyache for one day; one episode of loss of
consciousness for few minutes.
 Past medical history: transient weakness of left side of body and convulsive disorder since the
age of 8 months for which she was under treatment. Child also had delayed developmental
milestones.
 On examination a large port-wine stain involving both sides of face along the ophthalmic
and mandibular divisions of trigeminal nerve and neck region was present.
 On ophthalmological evaluation, she had bilateral megalocornea with vertical diameter of
14mm. Neuro retinal rim was unhealthy and nasal shifting of vessels was seen.

9.  There was hypotonia on left side of body and deep tendon reflexes were decreased over left
side of the body.
 Other systemic examination was normal.
 CT brain showed right cerebral hemisphere and left occipital atrophy with linear and
clumped gyral calcification.
 MRI brain showed right hemispheric atrophy with diffuse gyral enhancement involving right
cerebral hemisphere & left occipital lobe, enhancing choroid in both eyeballs suggestive of
choroidal angioma.

11. Sturge-Weber syndrome
 Rare sporadically occurring, congenital neurocutaneous disorder with an estimated frequency of
approximately 1 per 50,000 live births; There is evidence that it can be caused by somatic mosaic
mutation in the GNAQ gene on chromosome 9q21
 Characterized by intracranial leptomeningeal vascular angioma with unilateral facial nevus but in
our patient, port wine stain involved both sides of the face and extended up to the neck.
 Other clinical findings associated with SWS are seizures, glaucoma, hemiparesis and mental
retardation. About 25 to 56 percent of patients experience recurrent episodes of paroxysmal focal
neurological deficits in form of transient hemiparesis which may be due to vascular ischemia or
may be post-ictal in origin.
 The radiological hallmark is “Tram-line” or “Gyri-form” calcification.

12.  DDx: Klippel-Trenaunay syndrome- extensive capillary malformations associated with dysplastic
veins involve the limbs and trunk, often with hypertrophy of the affected extremity.
 The management of SWS is symptomatic and aimed at controlling of seizures, preventing stroke
like episodes, monitoring for glaucoma and using laser therapy for cutaneous capillary
malformation.
 There is increasing agreement among experienced clinicians that low dose aspirin may be
beneficial, with the rationale that antithrombotic therapy may prevent the progression of
impaired cerebral blood flow and hypoxic-ischemic neuronal injury.
 Neurologic function may deteriorate with age. As a result, approximately one-half of affected
adults are impaired, including those who initially were normal.

13. INHERITANCE
- Isolated cases
HEAD & NECK
Head
- Macrocephaly
Face
- Facial hemangiomata
Eyes
- Choroidal hemangiomata
- Glaucoma
- Buphthalmos
SKIN, NAILS, & HAIR
Skin
- Hemangiomata in at least first branch (ophthalmic) of trigeminal nerve
unilateral, occasionally bilateral
NEUROLOGIC
Central Nervous System
- Arachnoid hemangiomata
- Cerebral cortical atrophy
- Mental retardation
- Seizures
- 'Double contour' convolutional calcification on CT scan
MOLECULAR BASIS
- Caused by somatic mosaic mutation in the guanine nucleotide-binding protein q
gene (GNAQ, 600998.0001)

14. Case 3
 A 5 year old boy presented to our out-patient department (OPD) for blood group testing for school
purpose.
 On inspection the child was found to have white lock of hair bilaterally. Eyebrows and eyelids were
also hypopigmented.
 On detailed examination he was found to have sectorial heterochromia of both eyes.
 Second in order, he was born of non-consanguineous marriage, full term NVD without any antenatal
complications; His development was normal.
 Though obvious hearing impairment was not evident clinically, he was evaluated by concerned ENT
specialist and audiometry was done which was normal.
 Detailed ophthalmological evaluation including visual acuity and fundus examination were normal. There
was no dystopia canthorum (lateral displacement of the inner canthi) with W index being 0.9.
 Elder sibling also had similar feature of white forelock.

16. Waardenburg Syndrome
 Rare hereditary disorder with prevalence of 1 in 270,000 births.
 Waardenburg syndrome type 1 is an autosomal dominant auditory-pigmentary syndrome characterized
by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and
'dystopia canthorum‘
 4 main phenotypes:
 WS type 1: presence of dystopia canthorum.
 WS type 2: absence of dystopia canthorum.
 WS type 3: dystopia canthorum and upper limb abnormalities.
 WS type 4 (Waardenburg-Shah syndrome): additional feature of Hirschsprung disease
 WS 1 is caused by loss of function mutation of PAX3 gene.

17. Our index case had three of the major criteria - white lock of
hair, segmental heterochromia of iris and affected first
degree relative {the elder female sibling}. Diagnosed as a
case of Waardenburg syndrome type 1

18.  There is currently no cure for the syndrome.
 Being an autosomal dominant disease, WS-1 can recur in families and can have severe hearing
impairment which is the most dreaded complication.
 So early diagnosis in the index case can help to detect all the affected family members and can
even be offered genetic counselling and screening of the newborn babies for hearing
impairment and offering them social and vocational training and rehabilitation if needed at the
earliest.
 8 cardinal diagnostic signs: telecanthus, synophrys, iris pigmentation disturbances, partial hair
albinism, hearing impairment, hypopigmented skin spots, nasal root hyperplasia, and lower
lacrimal dystopia. Some patients with type 1 may not have dystopia canthorum, but that it is
present in 95 to 99% of patients with WS type 1.

19. HEAD & NECK
Face
- Smooth philtrum
- Decreased philtrum length
Ears
- Congenital sensorineural deafness
Eyes
- Laterally displaced inner canthi (dystopia canthorum) (95
99%)
- Increased intercanthal distance
- Blepharophimosis
- Hypertelorism
- Heterochromia iridis, complete or partial
- Hypoplastic iris stoma
- Hypopigmented ocular fundus
- Bright blue irides
- Synophrys
- Lower lacrimal dystopia
Nose
- Broad, high nasal root
- Wide nasal bridge
- Hypoplastic alae nasi
Mouth
- Cleft lip/palate
- Mandibular prognathism
CHEST
Ribs Sternum Clavicles & Scapulae
- Supernumerary ribs
GENITOURINARY
External Genitalia (Female)
- Absent vagina (rare)
Internal Genitalia (Female)
- Absent uterine adnexa (rare)
SKELETAL
Skull
- Aplasia of posterior semicircular canal on CT scan
Spine
- Sprengel anomaly
- Supernumerary vertebrae
SKIN, NAILS, & HAIR
Skin
- Congenital partial albinism (leukoderma) on face, trunk, or limbs
- Hypopigmented skin lesions
Hair
- White forelock
- White eyelashes and eyebrows
- Bushy eyebrows
- Premature graying of hair
ClinicalFeatures

20. INHERITANCE
- Autosomal dominant
NEUROLOGIC
Central Nervous System
- Spina bifida (less common)
- Myelomeningocele (less common)
MISCELLANEOUS
- Clinical variability seen in Waardenburg syndrome type
1
- Other variants of Waardenburg syndrome include
Waardenburg syndrome type 2, Waardenburg syndrome
type 3, and Waardenburg syndrome type 4
MOLECULAR BASIS
- Caused by mutation in the paired box 3 gene (PAX3,
606597.0001)

21. Case 4
 2 months old boy presented with generalized tonic clonic convulsions with
no history of trauma or fever.
 Investigations done at that time revealed Ca: 5.5 mg/dl (normal range: 9–
11 mg/dL), PO4: 7.9 mg/dl (normal range: 2.4–4.5 mg /dL), ALP: 142
U/L (normal range: 55 U/L–260 IU/L), PTH < 0.3 pmol/L (normal range:
1.2–7.2 pmol/L). CBC, LFT, RFT, and urine analysis were within normal
limits.
 Diagnosed as primary hypoparathyroidism and started calcium and vitamin
D therapy and convulsions were controlled.
 Birth history: full term, NVD, birth weight: 1.75 kg, 1st offspring of non-
consanguineous marriage.
 Follow up : severe growth retardation, height was at −6.7 SDS, weight was
at −5.3 SDS and BMI was at −4.2 SDS.
 The patient had typical facial dysmorphism, consisting of prominent
forehead, deep set eyes, abnormal external ears, microcephaly,
microphthalmos, thin upper lip, beaked small nose, micrognathism,
and small hands and feet. Systemic examination was normal.

22. HEAD & NECK
Head and face
- Microcephaly
- Micrognathia
- Prominent forehead
- Long philtrum
Ears
- Low-set ears
- Posteriorly rotated ears
Eyes
- Deep-set eyes
Nose
- Beaked nose
- Depressed nasal bridge
Mouth
- Thin lips
- Bifid uvula
GENITOURINARY
External Genitalia (Male)
- Micropenis
Internal Genitalia (Male)
- Cryptorchidism
SKELETAL
- Delayed bone age
- Patchy osteosclerosis
- Small hands and feet

23. SANJAD-SAKATI SYNDROME/
Hypoparathyroidism, retardation, and
dysmorphism (HRD)
 Rare autosomal recessive congenital disorder described in patients of Arab origin.
 Characterized by congenital hypoparathyroidism, severe prenatal and post-natal growth retardation
as well as mild to severe mental retardation. The common dysmorphic features of the syndrome are
microcephaly with prominent forehead, deep- set eyes, thin lips, depressed nasal bridge with
peaking of the nose, large floppy ear lobes and small hands and feet.
 Although some of the features resemble DiGeorge Syndrome, Kenny-Caffey Syndrome and familial
Hypoparathyroidism, absence of association with cardiac lesion, lymphopenia or skeletal
abnormalities makes it a distinct entity. Ocular examination helps to differentiate the Kenny-Caffey
syndrome (Nanophthalmos and corneal opacity) and SSS (only external ophthalmic features.)

24.  They are susceptible to severe infections including life-threatening pneumococcal infections
especially during infancy.
 Homozygosity and linkage disequilibrium to map the gene for this disorder to a 1-cM
interval on 1q42-q43 demonstrated that both autosomal recessive Kenny-Caffey syndrome
and SSS (HRD) are caused by mutations in TBCE gene
 Early recognition and therapy of hypocalcemia is important as is daily antibiotic prophylaxis
against pneumococcal infections.

25. INHERITANCE
- Autosomal recessive
GROWTH
Other
- Intrauterine growth retardation, severe
- Postnatal growth retardation
NEUROLOGIC
Central Nervous System
- Tetany
- Hypocalcemic seizures
- Mental retardation
- Ventricular dilatation, mild-moderate
- Hypoplasia of the anterior pituitary
- Thin corpus callosum
- Decreased white matter volume
- Delayed myelination
ENDOCRINE FEATURES
- Low parathyroid hormone
- Congenital hypoparathyroidism
- Growth hormone deficiency
IMMUNOLOGY
- Normal cell mediated immunity
- Recurrent bacterial infections
LABORATORY ABNORMALITIES
- Hypocalcemia
- Hyperphosphatemia
MISCELLANEOUS
- Allelic to Kenny-Caffey syndrome type 1
MOLECULAR BASIS
- Caused by mutation in the tubulin-specific chaperone E gene (TCBE, 604934.0001)

26. REFERENCES
 https://www.pediatriconcall.com
 http://omim.org/entry/241410
 PubMed
 https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.a.31122
 https://www.sciencedirect.com/science/article/pii/S1110663816300921
 UpToDate