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Page 120 Fichera et al. J Transl Genet Genom 2020;4:114-32 I http://dx.doi.org/10.20517/jtgg.2020.16

he showed severe psychomotor delay. His weight was 15 kg (< 3rd percentile), height was 99 cm (-4 SD),
and OFC was 44 cm (-4.2 SD). Physical examination revealed high frontal hairline, down-slanting palpebral
fissures, hypertelorism, depressed nasal bridge, mild malar hypoplasia, anteverted ears, deep philtrum,
and macrostomia [Figure 1B]. His hands were small with short fingers, bilateral clinodactyly of the fifth
finger, and bilateral single palmar crease. His feet were small with short toes, broad hallux, and bilateral
“sandal gap” [Figure 2B]. Other findings included mild hypotonia and joint laxity. Griffiths scale scores
revealed severe ID (IQ: 34; Performance: 34) with absent language. EEG recordings showed an excess of
fast rhythms particularly over anterior areas. During sleep, bursts of paroxysmal slow abnormalities were
present bilateral, diffuse, and prevalent in anterior left areas. Non-epileptic myoclonus was present both
during wakefulness and sleep. His behavior was characterized by impulsiveness. Array-CGH revealed a
13.7-Mb deletion of 1q24.2q25.3 [Supplementary Figure 1B].

Case 4
The 10-year-old patient was the first child born to 34-year-old healthy, non-consanguineous parents.
Familiarity for cleft lip/palate and deaf-mutism was recorded. He has a younger healthy nine-year-
old brother. The patient was delivered by caesarian section at 43 weeks of gestation after a pregnancy
characterized by IUGR and poor fetal movements. His birth weight was 2,900 g (-3 SD); length and OFC
were not recorded. Cleft lip/palate was surgically corrected at the age of one year. At the age of two years,
his psychomotor and language development was moderately delayed and characterized by inattentive-
hyperactive behavior. At the same age, left-side cryptorchidism was surgically corrected. Mild growth
hormone deficiency was documented but without the need for pharmacological treatment. When evaluated
at the age of 10 years, his weight was 24 kg (< 10th percentile), height was 120 cm (3rd-10th percentile),
and OFC was 49 cm (-3 SD). At neurologic examination, he presented global clumsiness and facial
dysmorphic features including triangular face, highly arched eyebrows, upslanting palpebral fissures, high
nasal bridge, short phyltrum, cleft lip and palate with malposition of incisors, arched palate, micrognathia,
and low-set ears. Mild calcaneovalgus foot was also noted. Leiter-R scores revealed moderate ID (IQ: 44)
with absent speech. ECG revealed mild mitral valve insufficiency. Brain MRI showed hypoplasia of the
corpus callosum. Array-CGH revealed a 22.4-Mb deletion of 1q24.2q25.3 [Supplementary Figure 1B].

Cases 5 and 6
The pedigree is shown in Figure 3.

Case 5 (II.1) and Case 6 (III.4) are with 1q24.3q25 deletion, while III.2 carries two microdeletions at
8q24 and Xp22.2 (see Supplementary Figure 2 for details), both maternally inherited (II:2). In paternal
grandparents (I.1 and I.2), the presence of 1q deletion was excluded by CMA.

Front and lateral views of Case 5 (A) and Case 6 (B). While Case 5, at the age of 38 years, does not show
any of the facial dimorphisms reported in patients with overlapping 1q deletion, his daughter (Case 6), at
the age of nine months, showed thin upper lip, microretrognathia, short neck, and microcephaly.

The index patient (III.2) was a four-year-old child born to a 27-year-old mother, who during pregnancy
suffered from preeclampsia and was treated with anticoagulant drugs (aspirin and heparin) for
thrombophilia and eutirox for hypothyroidism. The delivery was induced at 36 weeks of gestation for
oligohydramnios. His birth weight was 2,800 g (10th-50th percentile). The perinatal and neonatal period
was unremarkable despite feeding difficulties characterized by gastroesophageal reflux until the age of
nine months. He crawled at 10 months and walked alone at the age of 18 months. His speech development
was delayed and, at the age of four years, he was able to pronounce incomplete words. His behavior was
characterized by low frustration tolerance associated with heteroaggressivity and bruxism. A diagnosis
of autism spectrum disorder (ASD) was made (QS: 75, F 84.0 ICD 10, 299.00 ICD 9). CMA revealed two