8q22.2q22.3 Microdeletion Syndrome Associated with Hearing Loss and Intractable Epilepsy

Table 1

Clinical phenotype of the seven reported cases carrying an interstitial microdeletion of 8q22.2q22.3. Patient 8 is the new Colombian case reported.

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7	Patient 8
Sex	F	M	F	F	F	F	M	F
Age mother/father	20/21	24/30	38/36	35/31	n.d	n.d	22/25	38/37
Weeks of gestation	37	42	40	37	40	39 weeks and 4 days	41 or 42	36
Birth weight (g)	2,240 (-1.7 SD)	4,000 (+0.8 SD)	3,350 (-0.3 SD)	2,550 (-1 SD)	2,700 (-1.8 SD)	2,702 (-1.3 SD)	Over 3,600	1,800 (-2 SD)
Birth length (cm)	45 (-1.9 SD)	n.d	50 (-0.8 SD)	43.5 (-2.5 SD)	48 (-1.7 SD)	47.5 (-1.2 SD)	57 (+3.66 SD)	42 (-2 SD)
Birth OFC (cm)	32 (-1.4 SD)	36 (+0.1 SD)	34 (-0.7 SD)	31.5 (-1.7 SD)	33 (-1.5 SD)	33.5 (0.0 SD)	n.d	n.d
Age	6 years	3 years 6 months	8 years 6 months	8 years	20 years	8 years	40 years	10 years
Height (cm)	111 (-1.2 SD)	97 (-1 SD)	116 (-2.7 SD)	102.5 (-4.5 SD)	151	124.8 (-0.7 SD)	170.9	110 (-2 SD)
Weight (Kg)/BMI; (kg/m2)	20 (-0.6 SD)/16.2	16.1 (+0.3 SD)/17.1	20 (-2 SD)/14.9	15.4 (-2.9 SD)/14.7	73.5/32	24.35 (-0.8 SD)/15.6	99/33.9	17 (-1.5 DS)/14
OFC (cm)	48.5 (-1.6 SD)	49 (-1.2 SD)	48.7 (-2.1 SD)	46 (-3.9 SD)	53 (-1.4 SD)	51.6 (+0.5 SD).	59.7 (+3.45 SD)	46 (-2 SD)
Developmental delay/ID	Severe	Moderate	Severe	Severe	Moderate	Moderate/severe	Moderate	Moderate
Sits independents (Months)	12	n.d	Between 24 and 36	24	9	7	n.d	7
Walks independent; (Months)	27	17	60	90	24	24	13	30
First Words; (Months)	No words	n.d	No words	No words	18-20	46	n.d	24
Seizures	+	-	+	+	+	++	+	++
Autistic behavior	+	+	-	+	+	+	+	-
Temper tantrums	n.d	+	-	+	+	n.d	+	-
Sleep disturbances	+	n.d	-	n.d	+	n.d	n.d	-
Low sensitivity to pain	+	n.d	-	n.d	n.d	n.d	n.d	-
Autoaggressiveness	+	+	-	n.d	+	n.d	+	-
Restlessness	+	+	-	n.d	+	n.d	n.d	+
Poor facial expression	+	+	+	+	-	+	-	-
Blepharophimosis	+	+	+	+	-	-	+	+
Telecanthus	+	+	-	+	-	+	-	+
Ptosis	-	-	+	+	-	-	+	+
Epicanthus	+	+	+	n.d	-	-	+	+
Eyebrows	Sparse, broad	Rather sparse	Rather sparse	Bushy/ Mild Synofris	Mild Synofris	Sparse and wide	Sparse	Sparse
Flat nasal tip	+	+	+	+	-	Slightly	-	+
Down-turned corners of the mouth	+	+	+	+	+	-	+	+
Ears	Small ear	Poor modeled ears	Poor modeled ears	Low set posteriorly rotated	Small ears	n.d	Overfolded and asymmetrical in length	Low set posteriorly rotated
Hands/Feet	n.d	Short thumbs and toes	Short hands with proximal implanted thumbs, mild cutaneous syndactyly bilateral proximal radio-ulnar synostosis	Single crease, bilateral clinodactyly of the 2nd and 5th fingers	Small hands with tapering fingers, II–III cutaneous syndactyly of feet	n.d	n.d	Short hands and feet, short thumbs, bilateral fifth finger clinodactyly
Congenital malformations	-	Large hiatal hernia, pylorus stenosis glandular hypospadias	n.d	Diaphragmatic hernia	-	-	Congenital heart disease. Hypoplastic auditory canals	-
Minimal deletion size (Mb)	5.26	6.10	5.26	6.44	1.92	1.36	3.35	5.23

+ denotes feature present; - denotes feature absent; n.d. denotes not documented.
ID: intellectual disability.
In conclusion patients with a submicroscopic deletion of 8q22.2q22.3 are characterized by a facial phenotype with blepharophimosis, telecanthus, epicanthus, flat malar region, thin upper lip vermillion, and down-turned corners of the mouth. Other clinical manifestations associated with 8q22.2q22.3 deletion syndrome can be a moderate to severe developmental delay, language development delay, absent speech, deafness, microcephaly, seizures, short postnatal stature, and congenital diaphragmatic hernias, especially when FPM2 (Zinc Finger Protein, FOG Family Member 2) is involved [4]. Until the present report, there is not a clear correlation between the size of the deletion and developmental delay, short stature, microcephaly, or seizures (Table 2).