Dr.Rithwik Sunil, Dr. Praveena N Bhaskaran , Dr. C Jayakumar
AIMS KOCHI
One year old male child from Maldives presented with complaints of noisy breathing and abnormal shape of head since birth.
No h/o fast breathing, chest retractions,bluishness ,fever, loose stools, seizures, rash , dysuria
This is the 1st child of NCM and
antenatal growth scan showed microcephaly at 37 weeks
Natal: Term/LSCS /2.105kg and ba cried immediately after birth
Single surface double light) x 2 days was given as ba had jaundice
Developmental history –
Gross motor – stands without support and other components development assessment was normal
Vitals: stable, No pallor, icterus, cyanosis, clubbing, lymphadenopathy, edemaHead to foot examination:MicrocephalyEpicanthal fold inversionShort neckb/l blepharophimosis,[ptosis,epicanthus inversusExtensive hypo and hyperpigmented areas all over the bodyLeft hypoplastic preplaced thumbradial deviation of left forearmRight thumb preplacedRight simian creaseMultiple cafe au liat macules inguinal region hypopigmented patch – 4X3cm
Right hypoplastic thumbAuxology: Wt- 6.9 kg ( <-3SD), Ht- 67cm (-3SD), HC-40.5cm (<-3SD)Systemic Examination:
RS- mild stridor present ,normal air entry bilaterally and normal vesicular sounds
Skin – Hypopigmented patch present over thigh multiple Cafe au leu mqcule present over limbs , no rash / mucocutanesous bleeds
Other systems: normal
Investigations
Labs done were normal with no cytopenias or positive inflammatory markers.
MRI Brain: normal
EEG,USG Abdomen, ECHO- normal
BERA- normal
USG Abdomen: Left prominent renal pelvis(3.9mm)
Torch screenRubella IgG – 94(<5)IgM – 0.58Toxoplasma IgG – 0.8IgM – 0.07CMV IgG – 18.6(<6)IgM – 0.12HSV IgG, IgM – negativeMother noticed stridor at 3 months of ageMRI brain done at 4 months : normalKaryotyping – 46 XY Immunoglobulin heavy locus
Differentials considered were:
Drug- or infection-associated cytopenias
Immune cytopenias
Acquired aplastic anemia (AA)
Paroxysmal nocturnal hemoglobinuria (PNH)
Pearson syndrome
Myelodysplastic syndromes (MDS)
Fanconis anemia
Shwachman Diamond syndrome
Amegakaryocytic thrombocytopenia
Dyskeratosis congenita
Stress Cytogenetics done revealed sensitivity towards MitomicinC (MMC)and Diepoxy butane(DEB)
Based on the clinical features and stress cytogenetics results, a diagnosis of Fanconis anemia was considered
Child was then given a genetics consult where next generation sequencing was advised.
Parents were advised and counseled regarding the need for regular follow up along with the possibility of Bone marrow studies when cytopenias develop. They were also counselled regarding future risk of malignancies.
Fanconis Anemia
Fanconi anemia (FA) is a rare multisystem hereditary disorder resulting in the development of bone marrow failure in those affected and a predisposition to malignancy, including myelodysplasia (MDS), acute myeloid leukemia (AML), and epithelial cancers. The most common congenital anomalies in FA are skeletal and include absence of radii and/or thumbs that are hypoplastic, supernumerary, bifid, or absent.
Anomalies of the feet, congenital hip dislocation, and leg abnormalities can also be seen .
Skin hyperpigmentation of the trunk, neck, and intertriginous areas, café-au-lait spots, and vitiligo, alone or in combination, occur with similar frequency.
Short stature is common and in some patients is aggravated subnormal growth hormone (GH) secretion or hypothyroidism.
Male patients with FA may have an underdeveloped penis, undescended, atrophic, or absent testes, and hypospadias or phimosis, and all are infertile.
Diagnosis is through clinincal features and Stress cytogenetics.
Next generation sequencing can also be done to confirm the diagnosis
Take home message
Patients should be assessed for solid tumors at least annually, with a careful physical examination that includes comprehensive inspection of the skin, oral cavity, and other organs for unusual masses.After a certain age (e.g., 10 yr) or after hematopoietic stem cell transplantation (HSCT), fluoroscopic examination of the orolaryngeal cavity and occult fecal blood testing are also recommended. Beginning at menarche, female patients should be screened annually for gynecologiccancer. Administration of HPV quadrivalent vaccine to decrease the risk of SCC is advised.